Blog Archives

Approximately 3.5 million women in the U.S. are living with breast cancer, including more than 154,000 with disease that has spread beyond the breast to other parts of the body, known as metastatic breast cancer (stage IV). The outlook for non-metastatic breast cancer patients has overall improved, with an average five-year survival rate reaching close to 100 percent for people with stage 0 or I breast cancer, and 93 percent for people with stage II breast cancer.

The prognosis for those women diagnosed with metastatic breast cancer is not as promising. But, as research continues, progress is emerging. The percentage of women surviving five years with metastatic breast cancer (aged 15-49) doubled from 18 to 36 percent between 1994 and 2012.

“Sometimes metastatic breast cancer can be considered much more of a chronic disease,” said Denise A. Yardley, M.D., a senior investigator at the Sarah Cannon Research Institute in Nashville, TN. “I’ve seen a positive impact on patients who continue relatively normal lives despite their disease and treatment.”

DENISE A. YARDLEY, M.D.

DENISE A. YARDLEY, M.D., FROM THE SARAH CANNON RESEARCH INSTITUTE BELIEVES WE ARE SEEING PROGRESS IN THE TREATMENT AND PROGNOSIS OF METASTATIC BREAST CANCER.

Treatment Advances Are Constantly Occuring

There are many forms of metastatic breast cancer. Patients’ tumors can be either positive or negative for growth receptors, signaling the presence or absence of the known drivers of the disease. And they may or may not have disease driven by HER2 (human epidermal growth factor receptor 2) receptors. That complexity and the cross signaling from the HER2 receptor to other growth factor receptors, as well as the multitude of treatments available to treat metastatic breast cancer are part of the reason it has been a particularly difficult disease to treat. But translational researchers are making significant strides to further understand tumor biology and the genomics behind breast cancer subtypes.

The end result is a more tailored treatment approach based on a patient’s specific tumor biology and other clinical factors. With an expansion in targeted therapies, there is greater value in having patients’ tumors thoroughly examined so treatments are better selected. “We’re continuing to try to improve our precision medicine and really tailor treatments to what’s going on in that specific patient’s tumor,” Yardley said.

Doctors also have a better understanding of how to use the growing array of treatments. While combination therapy is used in early stages of breast cancer, recent studies have provided additional evidence on how to  sequence treatment options for their patients. We now also focus  on balancing symptom control with quality of life and partnering with our patients to make appropriate treatment selections at any given time.”

There’s every reason to be optimistic for patients facing the diagnosis and challenges of metastatic breast cancer today.

Preventing Metastasis from the Start

About 30 percent of women with early stage breast cancer eventually develop metastatic disease. So in addition to improving the treatment of metastatic breast cancer, researchers are trying to continue to improve the cure rate and thus prevent breast cancer from becoming metastatic in the first place.

Metastatic Breast Cancer TreatmentMost women with early stage breast cancer will have surgery during the course of their treatment. Now, many are also candidates for  a variety of systemic therapies, either before or after surgery, to reduce the number of potentially microscopic cancer cells left behind and prevent the disease from coming back. Chemotherapy  is usually reserved for patients at higher risk for a recurrence or metastasis.

“We want to make sure we’re appropriately recommending specific therapies but sparing patients who have a lower risk of disease recurring and becoming metastatic,” Yardley said.

By administering these medications earlier, when the disease is still operable, researchers aim to increase the cure rate and prevent—or at least delay—recurrence and metastasis in breast cancer patients.

More Work to Be Done

Admittedly, much work remains to be done, according to Yardley. Over the last 60 years, breast cancer survival rates have tripled, but metastatic survival rates have a long way to go before they reach that level.

Clinical trials play an essential role in exploring new treatments and approaches in metastatic breast cancer, and these trials continue to become more targeted as researchers learn more about the disease subtypes. For instance, while immunotherapies have not proven effective in studies for metastatic breast cancer in general, trials investigating immunotherapy in specific breast cancer subtypes such as triple negative breast cancer have shown promising activity. Thus, targeted treatments in combination with chemotherapy continue to demonstrate great promise.

“The science has become astounding, allowing us to manipulate the biology of metastatic breast cancer through very tailored approaches,” Yardley added. “There’s every reason to be optimistic for patients facing the challenges of metastatic breast cancer today.”

To learn more about a patient’s experience with metastatic breast cancer, read “How This Metastatic Breast Cancer Survivor Told Her Family About Her Diagnosis.”

More people are being diagnosed with Crohn’s disease and ulcerative colitis than ever before, but researchers aren’t exactly sure why. A variety of factors including genetics, weakened immune systems and the environment may be at play.

In this podcast produced for this year’s Crohn’s and Colitis Awareness Week, Cathy Ferrone, director of patient advocacy at Celgene, and Laura Wingate, senior vice president of Education, Support and Advocacy at the Crohn’s and Colitis Foundation, discuss the rise in worldwide incidence rates of inflammatory bowel disease and why research in this area remains so important.

 

 


CATHY FERRONE FROM CELGENE AND LAURA WINGATE FROM CROHN’S AND COLITIS FOUNDATION DISCUSS THE RISE IN INFLAMMATORY BOWEL DISEASE.

 

To learn more about the lifelong struggle of having an inflammatory bowel disease, read “What It’s Really Like to Live with Ulcerative Colitis.”

To explore the Crohn’s & Colitis Foundation’s resources available to patients, caregivers and health care professionals, visit their website at http://www.crohnscolitisfoundation.org/ or call 1-888-My-Gut-Pain.
 

Beta-thalassemia is a blood disorder, with more than 60,000 infants born worldwide with the disease each year. However, unless you live in Asia, India, the Middle East or the Mediterranean where beta-thalassemia is most prevalent, you may never have heard of this inherited blood disorder that disrupts the body’s ability to make hemoglobin.

But that may be changing as doctors in Europe and North America are increasingly encountering patients with beta-thalassemia. “We’re only now starting to deal with it, and there is a lot of work that needs to be done,” explained Dr. Maria Domenica Cappellini, a hematologist at the University of Milan in Italy, whose research focuses on the disease.

As hematologists gather for this year’s American Society of Hematology Annual Meeting in San Diego, Cappellini and other experts are sounding the alarm about the expanding prevalence of beta-thalassemia so that physicians and health systems everywhere can better prepare for an increasing number of patients with this genetic disorder.
 

Spreading Faster Than Ever

Beta-thalassemia is an inherited disease caused by mutations in a gene required for making a component of hemoglobin – a protein that carries oxygen in the blood. Those mutations either prevent or reduce the production of hemoglobin, which can cause a shortage of mature red blood cells and lead to anemia.

Dr. Maria Domenica Cappellini

DR. MARIA DOMENICA CAPPELLINI, A HEMATOLOGIST AT THE UNIVERSITY OF MILAN IN ITALY, BELIEVES MORE COUNTRIES NEED TO PREPARE FOR THE EXPANDING PREVALENCE OF BETA-THALASSEMIA.

Often times, children inherit the gene mutation from parents who are carriers but do not show any symptoms of the disease. In this scenario, the child has a 25 percent chance of developing beta-thalassemia and a 50 percent chance of being an asymptomatic carrier like their parents.

The mutations that cause beta-thalassemia are more common in Asia, India, the Middle East and the Mediterranean where they are found in up to 20 percent of the population. But the increase in modern migration means that cases are now cropping up more often in other regions.

Southern Mediterranean countries recognize the rise in patients with beta-thalassemia and have increased resources to meet the growing demand appropriately. While in Northern and Western Europe, health professionals and policymakers acknowledge this trend, they lack reliable data on the frequency and patterns of the disease just yet. Without data, it’s difficult to make the case for investing in programs to address the issue, which means patients struggle to find the right doctors.
 

Bracing for Beta-thalassemia

Many patients with beta-thalassemia require life-long regular blood transfusions and medication to reduce the levels of iron in their body. “These patients cannot produce enough mature red blood cells to transport oxygen throughout their bodies,” Cappellini said. “So transfusions are necessary for their survival.”

Understandably, beta-thalassemia treatment requires significant expertise and resources, including safe blood donations. Many countries are preparing their health care systems by improving resources for blood transfusions. “As migration throughout the world continues to change, health care systems will need to evolve rapidly to meet the needs of a more diverse population,” Cappellini said.

“I get daily emails from colleagues in other parts of Europe asking how to treat patients with beta-thalassemia,” Cappellini said. “We’re trying to make this information as accessible and comprehensive as possible.”

Beta-thalassemia is something that hematologists in North America and Europe need to get up to speed on and quickly.

Longer Term Solutions

We’re still a long way from being able to correct or erase the mutation that causes beta-thalassemia. Currently, the only available cure is a stem cell transplant, but many patients may not be eligible. Fewer than 10 percent of patients eligible for a stem cell transplant actually receive one, often due to high costs or a lack of a donor.

Meanwhile, researchers are constantly looking at other ways to improve treatment options and patients’ quality of life, including therapies that could reduce the need for red blood cell transfusions. Transfusion frequencies vary based on patient needs, sometimes requiring them to spend hours receiving treatment every couple of weeks.

Another long-term solution is prevention through carrier screening and education, and some countries have found success with this approach. For instance, Cyprus, Italy and Greece enacted mandatory premarital screening and genetic counselling in the 1970s and have subsequently achieved almost a 100 percent reduction in at-risk births.

Without mandatory screenings, health care systems rely on education to reduce the incidence of beta-thalassemia. “If we don’t educate more populations about how this disease is transmitted, we will continue to see an increasing number of carriers and an expanding prevalence of beta-thalassemia around the world,” said Cappellini. “Beta-thalassemia is something that hematologists in North America and Europe need to get up to speed on, and quickly.”

To learn more about beta-thalassemia, read “The Need for Safe Blood Donations for Beta-thalassemia Patients.”

New research has helped scientists better understand the more than 60 different molecular subtypes of non-Hodgkin’s lymphoma (NHL), revealing just how diverse and complex this group of blood cancers is. And with better understanding comes the potential for different treatment pathways, which clinicians anticipate seeing at this year’s American Society of Hematology (ASH) Annual Meeting.

“From a biological standpoint, molecular lymphoma subtypes are very different from one another,” said Dr. Georg Lenz, Director of the Department of Hematology, Oncology and Pneumology at the University Hospital in Muenster, Germany. “These complexities potentially warrant different treatment approaches.”

Expanding our knowledge of these unique molecular drivers may open the door for targeted treatment approaches. Dr. Lenz expects we will learn more about these approaches during the ASH congress.

Dr. Georg Lenz

DR. GEORG LENZ FROM THE UNIVERSITY HOSPITAL IN MUENSTER, GERMANY BELIEVES THAT UNDERSTANDING THE SUBTYPES OF NON-HODGKIN’S LYMPHOMA IS HELPING RESEARCHERS TO IMPROVE TREATMENT.

A Tale of Two Characterizations

NHL subtypes can be divided into two broad categories based on how quickly the disease progresses: they can either be indolent or aggressive. Indolent lymphomas, such as follicular lymphoma (FL), are usually slow-growing and represent up to 40 percent of all NHL cases. Aggressive lymphomas grow at a much faster rate, such as one of the most frequent subtypes, diffuse large B-cell lymphoma (DLBCL).
 

Fast Progress in Slow-Moving NHL

The treatment landscape for indolent NHL, which includes follicular and marginal zone lymphomas, has been evolving quickly. While many patients still receive chemotherapy, targeted therapies have been making headway. At this year’s ASH Annual Meeting, Lenz expects to see more data from trials of these investigational therapies in combination with—or instead of—chemotherapy, opening the possibility for chemotherapy-free treatment.

“While we see increased interest in chemotherapy-free treatments, these approaches still have serious side effects,” Lenz said. “We still have a lot of work to do in managing these toxicities.”

Fortunately, most patients with indolent NHL respond well to treatment, but about 20 percent of FL patients relapse rather early after initiation of therapy. Since each patient responds to treatment differently, clinicians need to adapt treatment approaches accordingly, particularly for patients who do not initially respond well.

“This could be the next step for patients,” Lenz said. “It’ll be a challenge for years to come, but hopefully, we’ll see some progress in predicting treatment responses at this year’s ASH.”

It has been challenging to translate the biological knowledge of NHL into clinical practice.

New Avenues in Aggressive NHL Subtypes

Meanwhile, researchers are still grappling with the genetic complexity of aggressive lymphomas. Even previously identified subtypes are evolving into a collection of unique subtypes. For instance, DLBCL can be further broken down into additional subtypes, including activated B cell-like (ABC) DLBCL and germinal center B cell-like (GCB) DLBCL.  Different treatment approaches for the two are being tested in clinical trials.

“DLBCL encompasses unique molecular subtypes that behave differently, both biologically and clinically,” Lenz said. “It has been challenging to translate the biological knowledge of NHL into clinical practice.”

One investigational option being studied in patients with relapsed or refractory DLBCL and other aggressive NHL subtypes is chimeric antigen receptor (CAR) T cell therapy.

“Results on CAR T cell therapy are encouraging. However, we need longer follow-up to correctly assess its efficacy,” Lenz said.

To learn how patients and doctors are partnering to make treatment decisions in lymphoma, read “Developing Confidence in Lymphoma Treatment Decisions.”

Over the past few decades, scientists have come to understand that the loss of brain tissue—categorized into grey and white matter—in people with multiple sclerosis (MS) is linked with disease worsening. But research is revealing that grey matter loss, in particular, may be closely associated with disability and cognitive impairment.

“Grey matter loss is one of the best predictors of disease progression in people with MS,” said Dr. John DeLuca, senior vice president for research and training at the Kessler Foundation. “Finally, we’re seeing data that may help us better understand the mechanisms that drive this disease.”

DeLuca is calling attention to the value of assessing grey matter and cognitive impairment in MS and what implications these findings may have in understanding the disease.

JOHN DELUCA, Ph.D.

JOHN DELUCA, Ph.D., FROM THE KESSLER FOUNDATION BELIEVES GREY MATTER LOSS IN THE THALAMUS CAN PREDICT COGNITIVE DECLINE IN PEOPLE WITH MS.

Grey Matter Loss Associated With MS Disability Progression

While researchers have known that grey matter loss is associated with long-term disability, a study published earlier this year has provided a more detailed picture of that connection.

The researchers looked at how specific patterns of grey matter loss were associated with disability progression in patients with MS using a standard MS disability scale (EDSS).

The researchers found the strongest relationship between disability progression and the loss of brain tissue in the thalamus, the largest area of deep grey matter, which transmits sensory information to other areas of the brain. In a post-hoc analysis of MRIs from 1,214 MS patients and 203 healthy controls, baseline thalamic volume loss increased risk of disability progression by 37 percent in relapsing MS.

“The research continues to provide more evidence that loss of grey matter is associated with increased disability,” he said. “And grey matter loss is seen most intensely in the thalamus of patients with MS.”

Probability of Disability Progression Due to Volume

Cognitive Impairment Shouldn’t Take a Backseat to Disability

The new study makes the case for grey matter loss as a predictor of disability progression in MS, but it did not look at cognitive function—which can also worsen as MS progresses. DeLuca wasn’t surprised. “Cognitive impairment just doesn’t get the same attention as disability in MS studies,” he said. “But it really should.”

Many patients agree. In a recent survey conducted by the Multiple Sclerosis Association of America and sponsored by Celgene, 27 percent of respondents said maintaining cognitive function was the most important consideration in the management of their MS. Only the prevention of disability progression was reported by more respondents (45 percent).

While cognitive impairment has been recognized in MS for more than a century, a test to measure cognitive function wasn’t developed until 2001. Researchers know that up to 65 percent of people with MS experience some level of cognitive impairment, and the National MS Society recently announced new recommendations for managing cognitive care for people with MS.

So could the same patterns of grey matter loss associated with disability also be related to cognitive impairment? It’s quite possible, according to DeLuca. “Thalamic damage already has an established relationship with cognitive decline,” he pointed out. “And grey matter loss is seen most intensely in the thalamus of patients with MS. So it’s probable.”

The more specific we can be regarding the role of grey matter loss, the better we can care for patients with MS.

Measuring Grey Matter Loss in Practice

So far, doctors don’t routinely use grey matter loss as a predictor of disability or cognitive impairment when caring for patients, but DeLuca believes that maybe they should consider it. “Grey matter loss could be a trigger for clinicians to watch their patients over time and monitor for potentially related problems,” he explained.

Given current evidence, DeLuca would like to see more trials differentiating grey matter loss from brain volume loss in general. But the main goal, of course, is to identify new ways to look at cognitive impairment. DeLuca is hopeful.

“I think we’ll start to see further research that show the correlation between grey matter and cognitive impairment as well as physical disability,” DeLuca said. “The more specific we can be regarding the role of grey matter loss, the better we can care for patients with MS.”

To learn more about how brain volume loss can affect patients with MS decades later, read “How Multiple Sclerosis Affects the Brain and CNS.”

Over the past year, doctors have seen promising results from studies investigating new treatment approaches using chemotherapy for patients with pancreatic cancer, a disease that remains among the deadliest of cancers. Yet 38 percent of pancreatic cancer patients received no treatment at all within one year of diagnosis, according to study findings.

“Those results are not surprising as therapy for pancreatic cancer is rarely curative,” said Gabriela Chiorean, MD, a gastrointestinal oncologist and researcher at the University of Washington. “Most pancreatic cancers are diagnosed at a stage where the goal is to prolong survival—not to cure the disease. Some physicians and patients may be less willing to choose treatment because of that.”

Chiorean believes that more patients with pancreatic cancer could benefit from and should be offered treatment for their disease. During this year’s Pancreatic Cancer Awareness Month, Chiorean is raising awareness of both this issue and the progress that’s been made in pancreatic cancer treatment.

The Harsh Reality of Pancreatic Cancer

Gabriela Chiorean, MD

GABRIELA CHIOREAN, MD, FROM THE UNIVERSITY OF WASHINGTON BELIEVES THAT DOCTORS SHOULD NOT GIVE UP ON PATIENTS WITH PANCREATIC CANCER BY NOT DISCUSSING THEIR TREATMENT OPTIONS.

While the statistics may seem dismal, they are improving. From 1993 to 2013, while the median overall survival for metastatic pancreatic cancer patients remained steady, more patients achieved long-term survival—defined as a year or longer. According to Chiorean, these survivors were diagnosed at a younger age and may have been more likely to receive treatment.

Chiorean believes that survival rates would further improve if more patients were offered treatment. But as research point out—many patients do not receive treatment. Chiorean’s personal experience backs the study findings; she frequently sees patients who were not offered treatment in other centers and are looking for a second opinion.

Another reason patients may not receive treatment is that pancreatic cancer is difficult to diagnose. As a result, 80 percent of patients are diagnosed at an advanced stage when curative treatments are not an option. By the time the cancer is detected, oncologists may be hesitant to offer treatment because they fear their patients are too fatigued or ill, and unable to tolerate treatment regimens, according to Chiorean. It may be the physician’s intent to relieve stress on both the patients and their caregivers.

Even more challenging, pancreatic cancers can only be removed less than 15 percent of the time. “If you can’t take it out of the body, eventually it will start spreading unless it has already spread,” Chiorean said.

Managing treatment toxicities and a patient’s quality of life can also make a difference, according to Chiorean. She tries to prevent side effects by adjusting treatment dosing as needed and continuously asks patients how they are feeling before each treatment.

“That’s where the art of medicine comes into play,” she said. “We’re not treating everyone the same.”

Early Screening for Pancreatic Cancer

Pancreatic cancer can present with broad gastrointestinal symptoms that can be diagnosed as peptic ulcer disease or irritable bowel syndrome, and sometimes it presents with new diabetes. “A clinician might treat patients for indigestion for a year, and then ultimately diagnose them with late-stage pancreatic cancer,” Chiorean said. “If a patient is losing weight and has new onset diabetes, they should be screened with an ultrasound or CT scan for pancreatic cancer.”

Researchers are working on ways to catch pancreatic cancer earlier. Imaging techniques to detect premalignant cystic neoplasms, and other benign conditions that may be precancerous, are being explored, as are biopsies followed by regular ultrasound screening for high-risk patients, including those with a family history of pancreatic cancer.

We’re learning more about the disease and can offer treatment options that allow patients to feel comfortable for as long as possible.

Pancreatic Cancer Care Is an Uphill Battle

Improving care for pancreatic cancer remains a struggle. The pancreas has limited blood supply, making it difficult for medications to penetrate it. But new treatment strategies are making in-roads. New therapy combinations are being used before and after surgery for patients with pancreatic cancer, and new approaches are being explored in clinical trials to make chemotherapy less intensive for some patients. Chiorean recommends clinical trials of pancreatic cancer treatments for eligible patients.

“Despite the statistics, there’s definitely hope in the future of pancreatic cancer treatment,” said Chiorean. “We’re learning more about the disease and can offer treatment options that allow patients to feel comfortable for as long as possible.”

To learn more about the patient experience with pancreatic cancer, read “Facing Each Day with Pancreatic Cancer, Hand-in-Hand.”

Most patients diagnosed with lymphoma discuss the possibility of chemotherapy with a healthcare professional at some point. Chemotherapy is a standard of care for many forms of lymphoma, but most patients will experience multiple relapses.

Chemotherapy is a broad spectrum treatment that stops cell growth and division throughout the body, which can lead to side effects. Chemotherapies cannot differentiate between cancer cells and normal cells, so they also attack fast-growing but healthy cells, such as hair follicles and the cells lining the gut. That damage can lead to both short and long-term side effects, such as fatigue, nausea, a compromised immune system, fertility loss and an increased risk of infection or a second primary cancer.

While the benefits of chemotherapy often outweigh the risks, patients are eager for alternative solutions. Thankfully, research continues to look at different treatment pathways.

Meghan Gutierrez

MEGHAN GUTIERREZ, CHIEF EXECUTIVE OFFICER OF THE LYMPHOMA RESEARCH FOUNDATION (LRF), EXPLAINS WHY RESEARCHERS ARE EXPLORING CHEMOTHERAPY-FREE TREATMENTS

“We are learning a great deal about lymphoma subtypes and making progress in the discovery and development of new approaches that may improve quality of life,” Meghan Gutierrez, chief executive officer of the Lymphoma Research Foundation (LRF), said. “There is meaningful interest in exploring potential new treatments and combinations, many of which are chemotherapy-free.”

Lymphomas are caused by changes in immune cells called lymphocytes. In patients with lymphoma, the body makes many of these defective lymphoma cells that may not be detected by normal immune cells, which can properly fight infection and disease, including cancer. Restoring the immune system’s ability to fight cancer is a growing trend that has led to the development of immunomodulatory therapies, which can boost the tumor-killing cells of the immune system.

Investigators continue to explore new approaches focused on stimulating the immune system for patients with lymphoma.

The inherent ability of some types of immune cells to attack tumors relies on “tags” called antibodies on the surface of cancer cells. This killing process is known as antibody-dependent cell-mediated cytotoxicity (ADCC). In fact, several approved lymphoma therapies are antibodies that attach to cancer cells, leading the immune system to better identify and attack them. Researchers are now studying whether combining these antibody therapies with immunomodulatory therapies might further enhance cancer-killing ADCC, without the need for chemotherapy.

With further understanding of how both of these types of treatment work, separately and in combination, there is a potential to improve outcomes.

“Investigators continue to explore new approaches focused on stimulating the immune system for patients with lymphoma,” Gutierrez said. “It’s an incredibly exciting time as research is constantly evolving.”

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While innovative therapies have helped improve the relative survival rate for patients with multiple myeloma, the disease remains incurable with most patients experiencing repeated relapse and ultimately becoming refractory to treatments. Today, research continues to delve into whether treating relapsed multiple myeloma with combination therapies may be an appropriate option for certain patients. More agents could also result in increased toxicities and patients must be monitored closely.

­At the 54th Annual Meeting of the American Society of Clinical Oncology (ASCO), new data regarding the use of triplet therapy for relapsed multiple myeloma were presented. Now four or more drug combinations are being examined as well. In this interview, Dr. Paul Richardson, the RJ Corman Professor of Medicine at Harvard Medical School and clinical program leader and director of clinical research at the Jerome Lipper Multiple Myeloma Center at Dana-Farber Cancer Institute, discusses the new data presented at this year’s ASCO meeting and how the future of relapsed multiple myeloma treatment could look.

DR. PAUL RICHARDSON

DR. PAUL RICHARDSON FROM DANA-FARBER CANCER INSTITUTE BELIEVES THAT WE WILL CONTINUE TO SEE PROMISING RESULTS FROM COMBINATION THERAPIES FOR RELAPSED/REFRACTORY MULTIPLE MYELOMA.

Why have triplet and quadruplet regimens become more frequently used to treat relapsed multiple myeloma?

“Multiple myeloma is a heterogeneous disease, which means that patients typically have multiple subpopulations of malignant plasma cells with different molecular profiles and characteristics. When patients with multiple myeloma are given a single therapy, some of these subpopulations recede while others may grow. This phenomenon is believed to contribute to treatment resistance and eventual relapse.”

“So the theory that combination therapies provide a multi-pronged attack to target multiple myeloma subpopulations may be a reason why we are seeing more relapsed multiple myeloma patients being treated with combination therapies. Quadruplet regimens are also being investigated for high-risk patients with particularly resistant multiple myeloma.”

How have data presented at this year’s ASCO meeting moved the field forward?

“At ASCO, we saw new data from clinical trials comparing triplet with doublet regimens for relapsed multiple myeloma. Those findings support the idea that if you throw a wider net around the illness early with a triplet, you may achieve greater clinical benefit. At the same time, as we continue to explore new combinations, we are finding more regimens that may be better tolerated by patients.”

Why do many of these combinations include immunomodulators?

“Immunomodulators are an integral part of multiple myeloma treatment in both the newly diagnosed and relapsed/refractory setting. These therapies have numerous effects on tumor cells, the immune system, and the tumor microenvironment which we believe leads to their anti-multiple myeloma activity. In fact, they constitute a foundation for therapy regimens in multiple myeloma.”

“At this year’s ASCO, we saw important new data from trials exploring the interactions between these therapeutic classes in the relapsed setting.”

Although the treatment of relapsed multiple myeloma remains an unmet medical need, we’re making progress. The data presented at ASCO on combination therapies and potential breakthrough approaches like CAR T cell therapy are particularly exciting.

How are researchers taking a more precision-focused approach to treating relapsed multiple myeloma?

“Choosing the most appropriate therapy based on the genetic causes of a disease makes sense but is challenging in multiple myeloma, because the cancer is so genetically unstable. For example, we sequenced the genome of one patient at diagnosis and identified over 5,000 disease-associated mutations. By the time he relapsed, we had found more than 12,000. When you have that number of genetic changes, targeting a single mutation will be unlikely to make much of a difference on its own.”

“To help address this problem, we have to take a modified precision medicine approach. Researchers are studying whether combining backbone agents such as immunomodulators and proteasome inhibitors that have broad success in the disease with more targeted agents and evaluating these combination regimens, and in particular with monoclonal antibodies.”

What are your thoughts on the future of relapsed multiple myeloma treatment following this year’s ASCO meeting?

“Although the treatment of relapsed multiple myeloma remains an unmet medical need, we’re making substantial progress. The data presented at ASCO on combination therapies and potential breakthrough approaches like CAR T cell therapy are particularly exciting. While the FDA approved CAR T cell therapies have already shown promise in other cancers, multiple myeloma is a much tougher nut to crack. So we’ll have to wait and see what happens with these trials in the longer term, but early data are encouraging.”

To learn more about the advances discussed at ASCO 2018, read “ASCO 2018 Preview: Precision Medicine, CAR T Cells and Immunomodulators.”

Dr. Richardson regularly provides input as a paid consultant for Celgene.

CHRISTINE FILLMORE BRAINSON, PHD, ASSISTANT PROFESSOR AT UNIVERSITY OF KENTUCKY MARKEY CANCER CENTER, EXPLAINS THE IMPLICATIONS OF RECENT DISCOVERIES IN NON-SMALL CELL LUNG CANCER SUBTYPES.

CHRISTINE FILLMORE BRAINSON, PHD, ASSISTANT PROFESSOR AT UNIVERSITY OF KENTUCKY MARKEY CANCER CENTER, EXPLAINS THE IMPLICATIONS OF RECENT DISCOVERIES IN NON-SMALL CELL LUNG CANCER SUBTYPES.

The two major types of non-small cell lung cancer (NSCLC), adenocarcinomas and squamous cell carcinomas, have long been considered two distinct diseases. But researchers are now discovering that these tumor types may have a much more complicated, intertwined relationship.

As researchers gather for the 2018 American Society of Clinical Oncology meeting, we reviewed the implications of these discoveries for the future of lung cancer treatment with Christine Fillmore Brainson, PhD, assistant professor at the University of Kentucky Markey Cancer Center.

What are some of the unanswered questions that continue to drive research in NSCLC?

We still don’t know which cells are the culprits — the “cells of origin” for different subtypes of lung cancer. That’s something our lab is trying to parse out in mouse models. Understanding the cells of origin may help us to develop treatments that specifically target these NSCLC subtypes.

We’re also trying to personalize treatment for lung cancer patients. At the University of Kentucky, when lung cancer patients don’t respond to chemotherapy, we sequence their tumor biopsy. This lets us understand the unique genetic combinations that contribute to their lung cancer. Then we consider the approved and investigational therapies that target those mutations.

How has our understanding of different types of lung cancer evolved recently?

We’re beginning to understand that there may be more plasticity in NSCLC subtypes than we had thought. Sometimes, a patient is originally diagnosed with adenocarcinoma. Then a second biopsy after treatment may reveal that those tumors have qualities of both adenocarcinoma and squamous cell carcinomas. Having a tumor that looks like both, which we call adenosquamous lung cancer, complicates things, and it has a poor prognosis. This transformation could be a factor in resistance to therapy in NSCLC.

Non-small Cell Lung Cancer Subtypes

Do we know what drives this change in the tumor cells?

We typically only see second biopsies after a patient has been treated with epidermal growth factor receptor (EGFR) kinase inhibitors. So that treatment might be driving the transformation in patients. Or it might also happen after chemotherapy. We don’t know because we don’t take that second biopsy then to look at it.

In a previous study, we showed that we could force this transition in mice through specific genetic changes.

How might this finding affect how doctors diagnose patients?

In the future, a diagnosis of adenosquamous lung cancer, rather than just adenocarcinomas or squamous cell carcinomas, might be common. And it might justify taking a second biopsy after chemotherapy. Right now, that’s not recommended, because often the patient isn’t doing well at that point, and you don’t want to add a lung surgery unless there will be a clear benefit.

Understanding the cells of origin may help us to develop treatments that specifically target these NSCLC subtypes.

If one NSCLC subtype can change into another, how could that affect treatment?

We’ve seen that targeted immunotherapies work well in squamous cell carcinoma. My laboratory is studying whether the transition to squamous cell carcinoma can make the patient’s cancer more susceptible to immunotherapy. We’re studying this in a mouse model right now. If we can push the transition toward squamous cell carcinoma with a targeted therapy, maybe we can boost the response to immunotherapy.

What does the future of lung cancer treatment look like?

Cytotoxic therapy, such as chemotherapy, and immunotherapy combinations are potentially going to be the future of NSCLC treatment. At ASCO, researchers will present studies that show more data on chemotherapy and immunotherapy combinations to treat adenocarcinomas. Combinations are being tested in clinical trials, and the Food and Drug Administration have approved a few combinations for specific circumstances. We see that some patients do much better when treated with immunotherapy and chemotherapy. So we should continue exploring combinations of immunotherapies with our standard therapies. Combinations seem to be one clear way to go forward.

To learn more about how immunotherapies may be a new partner for chemotherapy, read “The Evolving Role of Chemotherapy in Lung Cancer.”

For decades, researchers seeking to develop new treatment options for multiple sclerosis (MS) believed that it was primarily a disease of the brain’s white matter, but recent studies have highlighted that grey matter plays an important role as well. For instance, grey matter loss, known as atrophy, may be seen in early stages of the disease and is associated with worsening symptoms.

As part of this year’s efforts to raise awareness of the disease during World MS Day on May 30, Dr. Robert Zivadinov, professor of Neurology and director of the Buffalo Neuroimaging Analysis Center and Center for Biomedical Imaging at Clinical Translational Science Institute at the University of Buffalo, explains researchers’ evolving understanding of the role of grey matter damage in MS.

DR. ROBERT ZIVADINOV FROM THE UNIVERSITY OF BUFFALO BELIEVES UNRAVELING THE ROLE OF GREY MATTER IN MULTIPLE SCLEROSIS MAY HAVE IMPLICATIONS FOR FUTURE TREATMENTS.

DR. ROBERT ZIVADINOV FROM THE UNIVERSITY OF BUFFALO BELIEVES UNRAVELING THE ROLE OF GREY MATTER IN MULTIPLE SCLEROSIS MAY HAVE IMPLICATIONS FOR FUTURE TREATMENTS.

MS was previously considered to affect white matter primarily. How has that understanding evolved to include grey matter?

“About 15 years ago, improved imaging techniques revealed that large areas of grey matter were affected in patients. This evidence helped explain why some patients had such severe disease but relatively few damaged areas in the white matter, known as lesions.”

Are there specific regions of grey matter that are affected by MS?

“Not all parts of the grey matter are equally affected. There’s definitely significant involvement of the cortical layers of the brain’s grey matter, which is linked to symptoms such as fatigue, cognitive changes and memory loss.

“The deep grey matter is also involved in MS as well, and in particular the thalamus, which relays motor signals and regulates things like consciousness, sleep and alertness.”

“Some studies have found that grey matter atrophy correlates with disability, cognitive impairment and disease progression better than white matter.”

What do researchers know about the connection between the loss of grey matter, cognitive dysfunction, disability and MS progression?

“Many studies have found links between grey matter damage with both physical and cognitive impairment in patients with MS, including symptoms such as muscle control, sensory perception and memory. Some studies have found that grey matter atrophy correlates with disability, cognitive impairment and disease progression better than white matter lesions do.

“Studies also suggest that grey matter lesions occur rather early on, particularly in relapsing-remitting MS, even before white matter lesions appear. It could very well be a potential marker for predicting disease progression.”

What is preventing it from becoming a more useful predictor of disease progression?

“Grey matter lesions are less pronounced than white brain lesions, so doctors have difficulty seeing them on typical MRIs. Instead, we have to use advanced, highly sensitive MRI techniques to measure changes in grey matter, but those techniques aren’t available everywhere. They require specialized equipment and expertise that is typically only found in academic research centers. That is one reason why grey matter atrophy has had limited use in the clinic.”

What do we still not understand about grey matter atrophy in people with MS?

“We still don’t understand what causes the damage. Grey matter atrophy is associated with several genetic, viral and environmental risk factors, but we haven’t pinpointed the mechanisms yet.”

What can be done to reduce the risk of damage to grey matter?

“That’s the holy grail. Most MS trials weren’t necessarily designed to answer that question. We are going to have to change the design of MS trials. Instead of only using MRIs of white matter lesions as an endpoint, we’ll need more sensitive imaging techniques to monitor grey matter changes over time as well.”

To learn more about how MS affects the brain over a lifetime, read “How Multiple Sclerosis Affects the Brain and CNS.”

Dr. Robert Zivadinov is a paid consultant for Celgene.

Last week, scientists, physicians and patient advocates gathered in Chicago for the 2018 American Society of Gene & Cell Therapy (ASGCT) annual meeting to discuss results of recent trials for cellular immunotherapies, including chimeric antigen receptor (CAR) T cell therapies. These treatments have the potential to change the treatment paradigm in oncology, but obstacles remain for cancer centers seeking to take advantage of this new approach.

In this Q&A, Dr. Helen Heslop, director of the Center for Cell and Gene Therapy at Baylor College of Medicine, Houston Methodist Hospital and Texas Children’s Hospital, explains what was discussed at the meeting regarding the practical challenges cancer centers are facing when offering CAR T cell therapies to patients.

DR. HELEN HESLOP FROM BAYLOR COLLEGE OF MEDICINE EXPLAINS SOME OF THE CHALLENGES OF IMPLEMENTING CHIMERIC ANTIGEN RECEPTOR T CELL THERAPIES.

DR. HELEN HESLOP FROM BAYLOR COLLEGE OF MEDICINE EXPLAINS SOME OF THE CHALLENGES OF IMPLEMENTING CHIMERIC ANTIGEN RECEPTOR T CELL THERAPIES.

What types of centers are offering CAR T cell therapy?

“A variety of centers are setting up CAR T cell programs, including public and private, large and small, pediatric and adult cancer centers.

“Everyone is doing it slightly differently, so we need to share best practices regarding the practical nuts and bolts of implementation in three broad areas: setting up a program to offer CAR T cell therapies, what it takes to get accredited and issues with access and reimbursement.”

How is the administration of cellular immunotherapies different from traditional treatments?

“Giving a patient cell therapy is different than typical small molecules or biologics. The patient’s lymphocytes are separated from the rest of the patient’s blood cells and plasma in a process called apheresis. The lymphocytes are then sent to a central manufacturing to be genetically reengineered. The modified cells are then sent to the treating center as a frozen CAR T cell product. The product is then thawed and infused back into the patient.

“The cell collection process is more akin to a stem cell transplant, so centers that are currently performing stem cell transplants have most of the processes in place to offer CAR T cell therapies.”

And those processes would include?

“With cellular therapies, there is the risk of developing complications that require specialized management, such as cytokine release syndrome and neurotoxicity.”

About 40 centers in the United States are offering cellular immunotherapies. But that number could rise quickly.

How many centers are currently offering CAR T cell therapy?

“Right now, about 40 centers in the United States are offering cellular immunotherapies approved by the U.S. Food and Drug Administration to patients. But there are close to 200 transplant programs across the country, so that number could rise quickly if more centers attain Risk Evaluation and Mitigation Strategy certification per the individual product labels.”

What is the most significant challenge for centers in implementing these therapies?

“Aside from the clinical issues, the financial and administrative aspects and access to these new therapies for patients are also significant challenges. Hospitals have to create new processes for this new treatment paradigm and codes for the procedures involved with CAR T cell therapy administration are not yet available.”

What’s next for cellular immunotherapies?

“So far, CAR T cells have only been approved for specific relapsed or refractory diseases. One obvious question requiring careful investigation of risks and benefits is whether you can give CAR T cell therapy earlier in the course of therapy.”

To learn more about how CAR T cells may help immune cells identify cancer cells, read “Revealing Cancer Cells to the Immune System.”

More than 32,000 oncology professionals will soon gather in Chicago for the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting. This year’s meeting, with a theme of “Delivering Discoveries: Expanding the Reach of Precision Medicine,” promises to be the most exciting yet because researchers are further unraveling the different mechanisms by which cancer starts, grows and metastasizes, as well as how the immune system responds to it.

This progress is ushering in a new era of precision medicine, according to Wim Souverijns, Corporate Vice President of Global Marketing for Hematology & Oncology at Celgene. Much of the research Celgene will present at this year’s meeting includes updates on its chimeric antigen receptor (CAR) T cell therapy platforms, as well new data related its investigational pipeline across hematologic malignancies and solid tumors.

CAR T Cell Data Continue to Roll In

One area of personalized medicine with incredible potential in cancer is CAR T cell technology. This process involves a patient’s immune cells being collected, modified in a laboratory to recognize cancer cells and reinfused to attack the cancer.

At this year’s ASCO meeting, Souverijns is looking forward to seeing longer-term safety and outcome data for several clinical trials involving investigational CAR T cell therapies in relapsed or refractory patients with difficult to treat blood cancers like multiple myeloma and diffuse large B-cell lymphoma.

While these therapies come with great promise, their safety profile needs to be properly characterized to ensure appropriate use of these therapies, Souverijns explains. At ASCO he expects further insights about particular side effects such as cytokine release syndrome (CRS) and neurotoxicity.

“These longer-term data will help us to better understand these effects and how to manage them,” he said. “This will be crucial to realize the promise of these investigational treatments for patients.”

Three years ago, most patients were getting doublets, and people were questioning the need for triplets. Today, people are talking about quadruplets.

CAR T beyond Blood Cancers

The big hope is that CAR T cell therapies will be able to go beyond hematological malignancies and effectively target solid tumors as well. Preclinical data of CAR T cell therapies in solid tumors are emerging. The challenge, though, is that solid tumors often aren’t responsive to treatment simply because therapies physically can’t reach the tumor.

“CAR T also holds promise in solid tumors, but it’s going to be a much harder nut to crack from a technological and scientific perspective than with blood cancers,” Souverijns said. “The integration of Juno’s recently acquired CAR T cell science powerhouse with Celgene’s deep disease and cellular therapy expertise provides a great opportunity with these new investigational technologies for cancer patients.”

AT THIS YEAR’S AMERICAN SOCIETY OF CLINICAL ONCOLOGY MEETING, ATTENDEES WILL DISCUSS ADVANCES IN CANCER RESEARCH, INCLUDING ADVANCES IN CAR T CELL THERAPY AND COMBINATION THERAPIES BUILT ON THE FOUNDATION OF IMMUNOMODULATORS.

AT THIS YEAR’S AMERICAN SOCIETY OF CLINICAL ONCOLOGY MEETING, ATTENDEES WILL DISCUSS ADVANCES IN CANCER RESEARCH, INCLUDING ADVANCES IN CAR T CELL THERAPY AND COMBINATION THERAPIES BUILT ON THE FOUNDATION OF IMMUNOMODULATORS.

Triplets Becoming More Common in Multiple Myeloma

At last year’s ASCO conference, clinicians saw data combining immunomodulators with other therapies to treat diseases like multiple myeloma. Souverijns expects to see even more data from trials this year testing combination therapies. While these combinations used to focus on later lines of treatment when patients have exhausted other options, the new data are showing options for earlier patient segments as well.

More seems like it may be better as more triplet therapies are being approved and utilized, while even quadruplets are being tested now. This is something he expects will be discussed at length at the conference as doctors are realizing that adding new therapies to the foundation of an immunomodulator may drive better outcomes.

“Three years ago, most patients were getting doublets, and people were questioning the need for triplets,” Souverijns said. “Today, people are talking about quadruplet therapy. It’s amazing how quickly cancer care is progressing, making each ASCO more extraordinary than the last.”

For all the potential advancements, Celgene’s Vice President, U.S. Medical Affairs Teng Jin Ong, M.D., pointed to precision medicine at this year’s conference.

“Our increasing insight into the biology of cancer drives the discovery of new therapies that are targeting very specific cancer mutations and allow for greater improvements in outcomes for patients with such mutations,” said Dr. Ong. “We’ll remember 2018 as the tipping point for precision medicine and showing how it could work in practice.

To learn more about how CAR T cells may help immune cells identify cancer cells, read “Revealing Cancer Cells to the Immune System.”

 

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On this year’s International Thalassemia Day (May 8), the beta-thalassemia community is hopeful that advances in gene therapy may lead to new treatment options. While Dr. Antonio Piga from the San Luigi Gonzaga University Hospital in Torino, Italy, shares that hope, he believes gene therapy remains distant.

DR. ANTONIO PIGA FROM THE SAN LUIGI GONZAGA UNIVERSITY HOSPITAL BELIEVES THAT SLOWING DOWN THE OVERPRODUCTION OF INEFFECTIVE RED BLOOD CELLS COULD HELP PATIENTS WITH BETA-THALASSEMIA.

DR. ANTONIO PIGA FROM THE SAN LUIGI GONZAGA UNIVERSITY HOSPITAL BELIEVES THAT SLOWING DOWN THE OVERPRODUCTION OF INEFFECTIVE RED BLOOD CELLS COULD HELP PATIENTS WITH BETA-THALASSEMIA.

“Even with recent advances, gene therapy approaches for beta-thalassemia are less than perfect,” Piga said. “Gene therapy may be a viable treatment for a majority of patients in 20 years. But what do we do until then? What if we could correct the downstream process that is broken in beta-thalassemia?”

That process is the production of healthy red blood cells, which are highly specialized for supplying oxygen to tissues and organs in the body. Produced in the bone marrow, these cells mature into little more than shipping containers for a large, multi-part protein called hemoglobin.

Within hemoglobin, iron molecules are ideally positioned to grasp oxygen molecules and transport them throughout the body. Iron-bound hemoglobin complexes give red blood cells their signature color and are essential to their maturation and function.

DURING THE PRODUCTION OF RED BLOOD CELLS, (1) FUNCTIONAL HEMOGLOBIN IS PRODUCED IN THE BONE MARROW AND (2-3) PLACED INTO RED BLOOD CELLS, GIVING THEM THEIR SIGNATURE COLOR.

DURING THE PRODUCTION OF RED BLOOD CELLS, FUNCTIONAL HEMOGLOBIN IS PRODUCED IN THE BONE MARROW AND PLACED INTO RED BLOOD CELLS, GIVING THEM THEIR SIGNATURE COLOR.

But in patients with beta-thalassemia, mutations disrupt the production of working hemoglobin in the quantities needed, so red blood cells do not mature properly; instead, they are like pale and abnormal small bags. Most importantly, they can’t pick up enough oxygen from the lungs and drop it off throughout the body.

IN PATIENTS WITH BETA-THALASSEMIA, (4) MUTATIONS DISRUPT THE PRODUCTION OF WORKING HEMOGLOBIN, (5-6) LEADING TO AN OVERPRODUCTION OF ABNORMAL RED BLOOD CELLS THAT ARE PINK-HUED AND UNABLE TO TRANSPORT OXYGEN EFFECTIVELY.

IN PATIENTS WITH BETA-THALASSEMIA, MUTATIONS DISRUPT THE PRODUCTION OF WORKING HEMOGLOBIN, LEADING TO AN OVERPRODUCTION OF ABNORMAL RED BLOOD CELLS THAT ARE PINK-HUED AND UNABLE TO TRANSPORT OXYGEN EFFECTIVELY.

“This inability to make sufficient hemoglobin contributes to chronic anemia,” Piga said. “But another distinctive and aggravating aspect of the disease is that the bone marrow works up to 30 times above, even ineffectively, with a lot of negative consequences including bone deformities.”

Piga is exploring whether it’s possible to disrupt the signals that send the bone marrow into overdrive. The hope is to treat anemia by boosting the number of red blood cells that have sufficient hemoglobin. While Piga admits the strategy would not cure beta thalassemia, it could improve quality of life for many patients living with this inherited blood disorder.

We’re hopeful that we can reduce the need for costly, time-consuming transfusions for patients.

Currently, most patients with severe forms of the disease need regular blood transfusions to shut down the bone marrow’s production of ineffective cells and augment the supply of normal red blood cells. Transfusions are cumbersome, costly and associated with risks, and they can cause complications through all the extra iron from the transfused blood cells. Since the body has no natural way to expel this metal, which can be dangerous at high levels, patients must be treated with chelation therapy to remove the excess iron.

While work remains to be done to understand how to curb the overproduction of ineffective red blood cells and the potential in alleviating chronic anemia, Piga remains optimistic.

“We’re hopeful that we can soon reduce the need for costly transfusions for patients as we continue to search for a cure,” Piga said. “That’s the best message that I can give to the beta-thalassemia community on this year’s International Thalassemia Day.”

To learn more about why new treatments are needed to reduce the need for transfusions in anemia, read “Beta-Thalassemia: Current Treatments Not Enough.”

When Dr. Timothy Vollmer sees patients with multiple sclerosis (MS), they talk about the symptoms they are experiencing today. But Vollmer tries to get them thinking further down the road. Most people with MS are diagnosed between the ages of 20 and 40, but might not feel the full impact of the disease until their 60s.

“The best bet at slowing the progression of disability later in life is at the beginning of the disease,” said Vollmer, a neurologist at the University of Colorado Denver. “But many patients — and even neurologists — don’t fully understand how MS affects the brain over a lifetime and why brain preservation is important.”

The Death of the Neurons

DR. TIMOTHY VOLLMER FROM THE UNIVERSITY OF COLORADO DENVER BELIEVES THAT THE BEST WAY TO SLOW DISABILITY PROGRESSION LATER IN LIFE IS TO TREAT MULTIPLE SCLEROSIS EARLY.

DR. TIMOTHY VOLLMER FROM THE UNIVERSITY OF COLORADO DENVER BELIEVES THAT THE BEST WAY TO SLOW DISABILITY PROGRESSION LATER IN LIFE IS TO TREAT MULTIPLE SCLEROSIS EARLY.

Damage in the brain for patients with MS is driven at least in part by a critical component of the immune system called B lymphocytes, also known as B cells, which recruit other immune cells and cause an inflammatory reaction. Why B cells begin attacking neurons is not fully understood, but what can be clearly seen is the damage they leave behind in the form of lesions that appear as bright white spots on a patient’s magnetic resonance imaging (MRI) scan.

When Vollmer analyzes a patient’s MRI, he pays particular attention to the appearance of lesions in the grey matter of the brain, the region involved in muscle control and sensory perception. As the grey matter continues to be attacked, causing new lesions to develop, symptoms such as fatigue and memory loss become more common, and cognitive impairment tends to increase.

But lesions often don’t appear steadily and consistently throughout a patient’s lifetime. Instead, the number of lesions tends to be highest at the onset of MS and then decreases over time. By the time a person with MS reaches 60 years old, new lesions are relatively rare.

“We don’t know why these lesions appear to decrease over time,” Vollmer said. “But if we wait to treat patients, the damage has already been done and what we’re left with is an accelerated pace of brain volume loss.”

Neurological Reserve

By the age of 40, everyone’s brain begins shrinking due to the loss of neurons as a result of the normal aging process. However, brain shrinkage happens faster in people with MS; while healthy individuals lose 0.1 to 0.5 percent of their brain volume per year, people with MS lose 0.5 to 1.35 percent per year, a significantly faster rate than those without the disease.

It’s important that neurologists understand how MS affects the brain throughout a person’s lifetime.

The effects of this brain volume and neuron loss may not be immediately apparent, though, because their brains and central nervous system tap into a neurological reserve to supplement this decline. However, those reserves are then used up sooner and, coupled with the normal aging process, result in the increased cognitive impairment and disability seen in people with MS.

With this long-term understanding of how MS affects the brain and CNS, Vollmer is traveling to conferences, giving lectures and trying to drive an international consensus on the issue. He’s reminding his patients and colleagues that it’s important to focus on measuring not only relapses, but also lesions and brain volume loss.

“It’s important that neurologists understand how MS affects the brain throughout a person’s lifetime,” Vollmer said. “Then they will understand why treating patients early and encouraging healthy lifestyles is essential to improving their patients’ lives down the line.”

To learn more about the MS journey for patients, read “The Search Continues for More Multiple Sclerosis Treatment Options.”

 

When doctors evaluate if a treatment is working for one of their patients with ulcerative colitis (UC), an inflammatory bowel disease that causes damage to the mucosal layer of the digestive tract, they will ask their patient about symptoms, such as bleeding, diarrhea and pain. But when researchers are evaluating the effectiveness of potential new treatments in a clinical trial, they need to include an objective assessment of disease activity as well.

So researchers are increasingly using endoscopy, a procedure using a flexible tube equipped with a video camera to look at patients’ digestive tracts, and examining tissue samples removed during a biopsy under a microscope to determine how well the mucosa is responding to an investigational therapy. In this Q&A, Dr. Keith Usiskin, executive director at Celgene, explains how by combining these two measurements, an assessment of mucosal healing can be made.

DR. KEITH USISKIN, EXECUTIVE DIRECTOR AT CELGENE, BELIEVES THAT COMBINING ENDOSCOPIC AND HISTOLOGIC MEASUREMENTS PROVIDES A DETAILED VIEW OF MUCOSAL HEALING IN ULCERATIVE COLITIS.

DR. KEITH USISKIN, EXECUTIVE DIRECTOR AT CELGENE, BELIEVES THAT COMBINING ENDOSCOPIC AND HISTOLOGIC MEASUREMENTS PROVIDES A DETAILED VIEW OF MUCOSAL HEALING IN ULCERATIVE COLITIS.

Why is mucosal healing important?

“Ulcerative colitis causes massive damage to the mucosa, weakening blood vessels and, eventually, leading to ulcers. Doctors and researchers are finding that achieving mucosal healing correlates with a better quality of life and other measurable benefits for patients with UC.

“For instance, studies have found that patients with UC in remission and with no signs of microscopic inflammation are less likely to be hospitalized or to experience relapse, in which their UC symptoms return. The data isn’t as strong as we’d like just yet, but we see a definite trend beginning to take shape.”

How is mucosal healing assessed in UC trials?

“Organizations conducting UC clinical trials assess mucosal healing often use both endoscopic appearance — what a gastroenterologist sees regarding redness, inflammation and ulcers during an endoscopy — and histological appearance — what a pathologist sees under a microscope regarding inflammation when they examine a tissue sample from a biopsy.”

Why are both endoscopies and biopsies needed to assess mucosal healing?

“While UC causes mucosal damage continuously, not every part of the mucosa is affected to the same extent. So endoscopies provide researchers with a bird’s eye view of the mucosa throughout the entire rectum and large intestine, including regions that are very inflamed and those that are less so.

“But endoscopic appearance doesn’t tell you everything. Studies have found that up to 24 percent of patients whose mucosa looks good in endoscopic assessments still have evidence of microscopic inflammation when a pathologist looks at a biopsy taken from the mucosa. That inflammation suggests the mucosa still is not fully healed and that the patient is at higher risk for relapses.”

Mucosal Healing: An Increasingly Accepted Endpoint in Studies of Ulcerative Colitis Treatments

What constitutes mucosal healing in these assessments?

“Defining mucosal healing remains one of the biggest challenges in UC clinical studies. The medical community and regulatory agencies have not come to a clear consensus on what constitutes mucosal healing in UC.

“Several scoring systems have been proposed for endoscopic and histologic assessments, but researchers have not decided which should be used. In Celgene’s studies, we use a widely used index for disease activity by endoscopic assessment in UC developed by researchers at the Mayo Clinic and a grading scale for histological assessment in UC developed by Dr. Karel Geboes at the University Hospitals Leuven in Belgium. We classify mucosal healing as a Mayo score less than or equal to one and a Geboes histologic score of less than two.”

What are the challenges in assessing mucosal healing?

“Clinician bias has been one of the most significant limitations in assessing mucosal healing. If the patient says they’re doing great, the clinician is more likely to report that the mucosa looks better, even if it seems the same as before starting treatment. The inverse can be true as well. We use central readers who do not know the patient’s health status to eliminate that bias. They can grade the endoscopies and biopsies based solely on their best judgment and experience.”

“The combination of endoscopy and pathology assessment of biopsies is key to the assessment of mucosal healing.”

Does the invasive nature of this assessment affect patient retention?

“Some patients are hesitant to enter a clinical trial if there are too many colonoscopies or endoscopies. Clinical researchers try to limit that when designing protocols for studies to minimize procedures that patients may find uncomfortable.

“We try to make it clear to patients what is expected of them when they sign up for a clinical trial and limit the burdens as much as possible. But we still have to make these assessments to determine the efficacy of potential new treatment options for UC.”

What could improve the assessment of mucosal healing?

“In the future, we may identify biomarkers that correlate with clinical symptoms, benefits and outcomes for patients with UC. Celgene is participating in an initiative to identify such biomarkers, and one day, noninvasive biomarkers may eliminate the need for endoscopy or biopsies. Imaging techniques such as MRIs and CT scans also may prove useful to assessing mucosal healing in future clinical trials and in the clinic. But right now, the combination of endoscopy and pathology assessment of biopsies is key to the assessment of mucosal healing for both scientific and regulatory purposes.”

To learn more about clinical trials for ulcerative colitis and other inflammatory bowel diseases, read “The Importance of Clinical Trials for Inflammatory Bowel Disease.”

Building on a long history of cellular therapy development and buoyed by the advancement of significant programs in cellular immunotherapy, Celgene completed the first phase of a renovation at its Summit West campus that will house a state-of-the-art cellular immunotherapy manufacturing center.

The 135,000 square-foot facility was completed months ahead of the original plan and will enable the company to expand investigational programs and eventually the potential commercial launch related to bb2121, its chimeric antigen receptor (CAR T) therapy being developed for certain multiple myeloma patients in conjunction with its partner bluebird bio. With CAR T technology, immune cells are removed from a patient, genetically modified and multiplied and placed back into a patient to create an individualized therapy.

“We wanted to ensure that we had a patient-centric model that supports our goal of flawless execution and rapid, compliant production,” said Mayo Pujols, Vice President of CAR T Manufacturing and Technology for Celgene. “We aim to see every patient getting their therapy back in that manner and so it made sense for us to build the capability in house.”

Celgene has a long history of cellular therapy development through its Celgene Cellular Therapeutics business that investigated placenta-derived and other stem cell therapies in multiple diseases. Celgene’s expertise and capabilities in cell therapy development and manufacturing have continued to be leveraged at its facility in Warren, NJ, where bb2121 has been manufactured thus far for clinical trials.

“We are proud to be able to contribute to the mission of improving the lives of patients with multiple myeloma,” said Greg Russotti, Ph.D., Celgene’s Vice President of Cell Therapy Process and Analytical Development. “Due to the infrastructure that we have been able to build over the years and the focus and investment from our leadership in cellular therapy processes and manufacturing, we are well-positioned to help accelerate this important area of science.”

In recent years, Celgene has expanded its commitment to this important research through multiple partnerships in the area of cellular immunotherapy. With bluebird, the company is collaborating to develop bb2121 as a potential therapy for previously treated multiple myeloma patients who express b-cell maturation antigen (BCMA) – bringing together two of Celgene’s historical areas of expertise in cellular therapy and multiple myeloma. Additionally, the company has partnered with Juno Therapeutics to develop CAR T therapies targeting the CD19 protein, and recently announced a definitive agreement to acquire Juno. These therapies are part of a potential new wave of treatments that aim to engage the patients’ immune systems to help identify and fight cancers.

Importantly, the establishment of this new facility reinforces Celgene’s growth in the city of Summit and the strong relationship with the community and state of New Jersey that may result in hundreds of new jobs over the next three years. For more information – visit our CAR T careers page at https://www.celgene.com/careers/car-t-opportunities/

“Each individual involved in this project, from the design, to the construction, to the activities to come, has pushed forward with the idea that what we do here may have a significant impact on the lives of patients,” said Joanne Beck, Ph.D., Celgene’s Executive Vice President, Global Pharmaceutical Development and Operations. “We are partnering with many state and national organizations, such as the New Jersey Innovation Institute, to identify, hire and train the workforce needed to staff this facility. We see it as a huge competitive advantage to be based here, in the State of New Jersey, having access to both state and national talent pools and to the disruptive innovations needed to bring this exciting new technology forward.”

For more information, see our information sheet here.

BB2121 and the CAR T therapies targeting the CD19 protein are investigational therapies.  Neither is approved for any indication by any regulatory authority. 

New Jersey is well-positioned for strong economic growth, and biopharmaceutical innovation is a significant driver of that potential. In 2011, the biopharmaceutical industry supported 322,049 direct and indirect jobs and created $87 billion in economic output in the Garden State. To ensure a high-growth N.J. economy for the future, the biopharmaceutical industry is helping to strengthen the state’s ecosystem of innovation by supporting emerging companies, job growth and pro-innovation policies.

“Historically, New Jersey has been a powerhouse in the biopharmaceutical industry,” said Debbie Hart, president and CEO of BioNJ, a non-profit that promotes the state’s biotechnology industry. “Because of its strong foundation in life sciences, increasing early-stage medical innovation is one of the greatest growth opportunities in New Jersey.”

One reason for New Jersey’s historical and continued leadership in the global biopharma industry is its highly skilled and educated workforce. The state has skilled biopharmaceutical talent and more scientists and engineers per square mile than anywhere else in the world. This workforce is supported by the five research universities,13 teaching hospitals and four medical schools that call New Jersey home.

Location also makes New Jersey attractive to biotech companies, given its proximity to important collaborators, which include the many established pharmaceutical companies within the state, the U.S. Food and Drug Administration and the National Institutes of Health a train ride away in Maryland, and Wall Street and venture capital across the river in New York.

Startups are particularly important in driving medical innovation in New Jersey’s biopharmaceutical industry. The majority of treatments approved in recent years originated in companies outside of the 30 largest biopharmaceutical firms; 2016 followed that trend, with more than 60 percent of approved therapies coming from companies with a significant New Jersey footprint.

Incubators serve an important role in helping startups establish themselves and grow, providing resources that would otherwise be unavailable

While New Jersey has the right ingredients to attract biopharmaceutical startups, its entrepreneurial ecosystem has the opportunity to offer even better support to home-grown startups, through incubators and business accelerators that offer resources such as funding, mentoring, workspace or equipment to young companies. Currently, New Jersey has 15 business incubators and accelerator programs compared with 375 for California and 179 for New York.

DEBBIE HART, CEO AND PRESIDENT OF BIONJ, BELIEVES NEW JERSEY’S BIOPHARMACEUTICAL INDUSTRY HAS THE POTENTIAL TO DRIVE THE STATE’S ECONOMIC GROWTH.

DEBBIE HART, CEO AND PRESIDENT OF BIONJ, BELIEVES NEW JERSEY’S BIOPHARMACEUTICAL INDUSTRY HAS THE POTENTIAL TO DRIVE THE STATE’S ECONOMIC GROWTH.

“Incubators serve an important role in helping startups establish themselves and grow, providing resources that would otherwise be unavailable to such young companies,” Hart said. “Looking at the biopharma industry in New Jersey, more incubators can certainly help increase early-stage innovation.”

Recognizing this opportunity, Celgene has launched the Thomas O. Daniel Research and Collaboration Center on its campus in Summit, New Jersey. The new center will provide state-of-the-art facilities and resources for high-potential scientists to build on their preclinical research in the important effort to discover innovative therapies for patients with unmet medical needs.

“With its iconic brand and cutting-edge science, the Thomas O. Daniel Research Incubator and Collaboration Center has the potential to attract, create and support companies that will produce the world’s next generation of therapies and cures,” Hart said. “Those treatments will help cut the overall cost of health care, which will benefit the economy, society and—most importantly—our patients.”

Prospective researchers, entrepreneurs and companies interested in joining the Incubator will submit applications for residency on the webpage within the Collaboration Center, which will be reviewed by a Celgene selection committee.

“The HealthCare Institute of New Jersey (HINJ) congratulates Celgene on the launch of its incubator, which will enhance New Jersey’s expanding innovation ecosystem,” said Dean J. Paranicas, President and Chief Executive Officer of HINJ.  “We look for this exciting initiative to create opportunities for new life sciences companies to develop novel treatments and cures that will benefit patients everywhere.”

To learn more about  the Thomas O. Daniel Research Incubator and Collaboration Center  and find out how you can apply, visit CelgeneIncubator.com.

The public often only sees the outside symptoms of plaque psoriasis: raised, red patches of skin covered with silvery scales. But the “Psoriasis Inside Out” theme of this year’s World Psoriasis Day (October 29) implores us to look at the “less visible” aspects of the disease.

New research is shining a light on one of those hidden characteristics of psoriasis: the increased risk of developing other diseases. Comorbidities associated with psoriasis include psoriatic arthritis, depression, diabetes, cardiovascular disease and metabolic disease.

Dr. Steven Feldman, a dermatologist practicing at Wake Forest University, explains that the presence of psoriasis comorbidities can affect a patient's health and their care.

Dr. Steven Feldman, a dermatologist practicing at Wake Forest University, explains that the presence of psoriasis comorbidities can affect a patient’s health and their care.

The presence of these comorbidities can not only impact a patient’s health but also affect their care. “For example, if a patient has a comorbidity of diabetes or liver disease, certain medicines may not be the most appropriate choice of treatment because they could increase the risk of liver damage,” explained Dr. Steven Feldman, a dermatologist practicing at Wake Forest University.

Although physicians who treat patients with psoriasis may be aware of comorbidities, dermatologists often focus on the skin, and other specialists may not pay attention to psoriasis as they focus on the particular disease or condition that they have expertise in. As a result, the medical community has struggled to understand the full extent of comorbidities in psoriasis patients.

To paint a clearer picture, Dr. Feldman and his colleagues analyzed insurance claims data from over 460,000 Americans diagnosed with psoriasis from 2008 to 2014. They found that 46 percent of those psoriasis patients were also diagnosed with high cholesterol, 42 percent with high blood pressure and 18 percent with depression. Other common comorbidities in this psoriasis population included diabetes, obesity and heart disease.

“While this approach is good, it’s not perfect,” Dr. Feldman explained. “For instance, if people don’t go to the doctor, then their psoriasis or their comorbidities would not be detected in studies.”

People with psoriasis should have regular health exams and screening tests to monitor their weight, blood pressure and cholesterol.

While the study provides a clearer picture of the burden of comorbidities, the relationship between psoriasis and these coexisting diseases remains less clear. So far, researchers have identified some potential contributing factors including common inflammatory pathways, cellular mediators and genetic susceptibility.

“Also, people living with psoriasis can make lifestyle choices that could reduce their risk of comorbidities,” Dr. Feldman said. “For instance, exercise and a healthy diet may help to prevent cardiovascular disease for people with psoriasis.”

The Most Prevalent Comorbidities in Psoriasis Patients

REFERENCE: SHAH KAMAL, MILLAR’S LILLIAN, CHANGOLKAR ARUN, FELDMAN STEVEN R.. REAL-WORLD BURDEN OF COMORBIDITIES IN US PATIENTS WITH PSORIASIS. JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY. 2017;77.

While dermatologists commonly screen for comorbidities such as psoriatic arthritis and depression, screening for other comorbidities such as cardiovascular disease is often done by the patients’ primary care providers.  Even though we do not understand the underlying factors that link these diseases, the fact remains that it’s important for patients and physicians to be aware of these comorbidities. Increasing awareness can help these psoriatic disease comorbidities and their risk factors from being overlooked and could potentially lead to earlier diagnosis and management.

“We don’t have enough research to know fully how comorbidities should affect our treatment,” Dr. Feldman said. “But given the increased risk of cardiovascular disease, people with psoriasis should have regular health exams and screening tests to track their weight, blood pressure and cholesterol.”

To learn why it’s important for psoriasis patients to obtain access to their recommended medications immediately, read “Psoriasis Patients Deserve Their Prescribed Therapy Without Delay.”

Many people living with moderately to severely active inflammatory bowel disease (IBD) are looking for additional treatment options to help them to cope with the physical and emotional burdens of their disease. Therapies called biologics that target a protein relevant to the immune system called tumor necrosis factor (TNF) are effective for many IBD patients. However, not everyone responds to these treatments. Now, investigational therapies that target other immune pathways are showing promise in clinical trials.

Dr. Brian G. Feagan, director of clinical trials at the Robarts Research Institute, SAYS the Inflammatory bowel disease medical community is increasingly interested in therapies that target sites of inflammation.

Dr. Brian G. Feagan, director of clinical trials at the Robarts Research Institute, SAYS the Inflammatory bowel disease medical community is increasingly interested in therapies that target sites of inflammation.

As more data on these IBD therapies come out of this year’s World Congress of Gastroenterology at ACG2017, Dr. Brian G. Feagan, director of clinical trials at the Robarts Research Institute, explains why the medical community is increasingly interested in therapies that target pathways associated with inflammation in the two most common forms of IBD, ulcerative colitis and Crohn’s disease.

Why is it important to develop targeted therapies for patients with IBD?

“Before biologic therapies were approved for IBD, we relied on steroids and immunosuppressive agents that broadly suppressed the immune system. We didn’t know exactly how these treatments worked but did know that they hit many different pathways. They were not very selective. For some patients whose ulcerative colitis or Crohn’s disease is caused by a particular pathway, these broad-spectrum agents may or may not hit that pathway, leaving some IBD patients without an effective treatment.”

People feel like they cannot plan their lives with the disease, but the continued investment in research is giving them hope.

How did the biologics change IBD treatment for patients?

“The biologics target a single protein that plays a role in the development of IBD, called TNF. Before the success of these anti-TNF therapies, the medical community didn’t think that blocking a single molecule or pathway would be effective. They believed that a combination of pathways was responsible for disease and that broad-spectrum therapy was needed. Clinical trials proved that theory wrong, at least for some patients. We have learned a lot about TNF blockers in the last 20  years.”

To learn why researchers must continue to explore new treatment options for IBD, read the “World IBD Day: Current Treatments for IBD Not Meeting Patient Needs” infographic.

To learn why researchers must continue to explore new treatment options for IBD, read the “World IBD Day: Current Treatments for IBD Not Meeting Patient Needs” infographic.


How have advances in understanding IBD opened the door for additional targeted therapies?

“Now that we know a single pathway can make a difference, as with TNF, researchers have started to look for other specific pathways associated with IBD. We are learning more about how these pathways control the immune response, interact with bacteria in our gut and are associated with complications of the disease, such as blockages in the intestine (strictures) and inflammatory tracts between the bowel and other organs, most commonly the skin (fistulas). This focus on specific pathways has evolved out of oncology, where researchers look for disease-related pathways and then use therapies that target specific pathways in individual patients. We haven’t quite gotten there in IBD, but that is the goal.”

Why is new research important for patients?

“People with ulcerative colitis and Crohn’s disease deal with substantial mental and social disabilities. The embarrassment of having IBD can negatively affect their lives. People feel like they cannot plan their lives with the disease, but the continued investment in research is giving them hope.”

To learn why researchers must continue to explore new treatment options for IBD, read the “World IBD Day: Current Treatments for IBD Not Meeting Patient Needs” infographic.

In 2009, a patient with acute myeloid leukemia (AML) was the first person with cancer to have his or her whole genome sequenced, helping scientists to learn more about the molecular drivers of the disease. Despite the knowledge gained, researchers have struggled to develop therapies that specifically shut down those drivers.

But this year brings hope for patients with AML, with the approvals of several new treatment options, including therapies that target specific molecular mutations. Dr. Gwen Nichols, chief medical officer for the Leukemia & Lymphoma Society (LLS), believes that these targeted therapies are helping to usher in the era of precision medicine in AML. As we recognize Blood Cancer Awareness Month, Dr. Nichols explains the challenges of translating knowledge into treatments and why she is excited about the future of precision medicine in AML.

Dr. Gwen Nichols, chief medical officer for The LLS, is hopeful about the future of precision medicine in AML.

Dr. Gwen Nichols, chief medical officer for The LLS, is hopeful about the future of precision medicine in AML.

Why has treating AML remained a challenge?

“AML is a complex and dynamic disease that really needs a precision medicine approach to treat appropriate patients. Some patients diagnosed with AML will respond to standard chemotherapy regimens, but most will relapse. Chemotherapy targets highly proliferating cells but may be missing the cells that initiated the AML. Those cells remain behind, recover and can cause the disease to come back in AML patients. This is one reason why the five-year survival rate for AML patients remains low at just 27 percent.

Why has it been challenging to develop targeted therapies for AML?

“When the AML genome was sequenced, researchers thought they were going to find single mutations that drive the disease. They believed that if you got rid of this single molecular abnormality, you could get rid of the disease. We have found a few of these mutations in other cancers, such as in the Bcr-Abl tyrosine kinase in chronic myeloid leukemia. But over the last decade, we’ve learned that some cancers, including AML, are more complex and driven by multiple factors. So an effective therapy targeting one mutation won’t be the end of the story because it’s only one piece of the puzzle. As we work toward the future of precision medicine, we need to look at multiple targeted therapies in combination.”

 AML is a complex and dynamic disease that really needs a precision medicine approach to treat appropriate patients.


What type of diagnostics would you like to see to facilitate precision medicine in AML?

“In a perfect world where it costs nothing and can be done rapidly, you would sequence a patient’s genome as frequently and as completely as possible. The targeted sequencing that doctors are doing for AML patients today makes the most sense because that information can help determine diagnosis and prognosis. But I fear that we may be missing valuable information by not sequencing more of our patients’ genomes. We also need to sequence at intervals to make sure the disease has gone away and again when there’s evidence that the disease is coming back. We can’t assume that it’s the same [form of the] disease when it returns.”

How do the clinical trial designs need to change for precision medicine?

“In diseases such as AML, it’s clear that there are subsequent mutations as the disease progresses and that the disease becomes more complex as it evolves. Most therapies are first tested in patients with relapsed or refractory disease, but you cannot expect a targeted agent to be effective when other driving mutations have arisen. This is a recipe for failure. We may be throwing out therapies that could benefit patients because we are testing them at a time when the disease is so complex that there’s little hope for a single therapy to be effective. That’s why the LLS’ Beat AML Master Trial is focused on newly diagnosed AML patients.”

What needs to happen to truly enable precision medicine in AML?

“The last couple of months have been exciting with several new therapies introduced for AML. We are seeing real progress toward that now with this first wave of targeted therapies. With over 700 clinical trials active or recruiting in AML, there is certainly more to come. But the hope would be to have several different therapies available that target all the drivers of AML. These therapies will not be developed on their own. We need to think about the best way to help facilitate the future of precision medicine through novel trial design and combinations.”

For more information on the progress of precision medicine, read “Getting Patients Access to ‘Precision’ Medicine Is Crucial.”