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.