Blog Archives

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 http://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.”

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.”

Alan F. List, MD, president and CEO of the Moffitt Cancer Center in Tampa, has made many contributions to hematology. List remains focused on what he has to offer the hematology field, so, last December, when he was recognized with the 2016 Celgene Career Achievement Award, he was humbly grateful.

Alan F. List, MD, president and CEO of the Moffitt Cancer Center in Tampa, was recognized with the 2016 Celgene Career Achievement Award.

Alan F. List, MD, president and CEO of the Moffitt Cancer Center in Tampa, was recognized with the 2016 Celgene Career Achievement Award.

Celgene is committed to supporting investigators who conduct hematology research and has established the Celgene Awards, comprised of the Career Achievement Award, Young Investigator Award, and Future Leaders in Hematology Award to recognize those investigators who have made significant contributions to hematology research. In addition to acknowledging the winners, the recipients’ institutions receive a grant from Celgene to continue efforts in hematology research and education.  An independent selection committee selects the institution based on the submissions received.

As nominations are being accepted for the 2017 Celgene Awards for Clinical Research in Hematology, Dr. List shares what continues to excite him about the hematology field, what he attributes his success to and where he thinks research is headed.

2016 Young Investigator AwardWhat did the recognition of your research through the Celgene 2016 Award mean to you?

“This award is a recognition of all the work that my collaborators and I have done together. Nothing that I have achieved thus far has been the result of one individual. It’s always been a collaborative effort.”

Which of your contributions are you most proud of?

“Three things come to mind. The first is my work in developing a treatment option for MDS. In 2001, I was investigating the role of angiogenesis — the formation of blood vessels — in the bone marrow of MDS patients. That research led me to explore whether existing therapies that slow the growth of blood vessels could stop the disease from getting worse. I applied for a grant and conducted a clinical trial that led to a new treatment option.

“The second is my work on multidrug resistance in MDS and high-risk acute myeloid leukemia (AML). We tested a potential therapy and took it to a phase III trial. That study remains the only one to show a survival benefit in high-risk AML patients.

“The third is my work to help speed up findings for the next generation. At the Moffitt Center, I’ve mentored some very bright researchers.”

2017 Celgene Awards: Nominate a Colleague Today!What inspired you to pursue a career in hematology?

“It seemed that there was so much potential for research in bone marrow-based malignancies such as MDS and AML. Researchers can access the disease directly through a bone marrow aspirate or by simply drawing blood from patients and studying the cells. That’s difficult to do in solid tumors.”

“Also the notion that the hematologist serves as both physician and pathologist creates an ideal opportunity to optimize insight into the disease pathology. You understand the case better than anyone as the physician, so you are more likely to have insights when reading the bone marrow.”

This award is a recognition of all the work that my collaborators and I have done together. Nothing that I have achieved thus far has been the result of one individual.

Celgene 2016 Future Leaders in Hematology AwardsWhat were your biggest career challenges?

“For everyone in research, funding is the greatest challenge. It became an even greater challenge for physician researchers like me in the ‘80s and ‘90s. At that time, the National Institutes of Health (NIH) began prioritizing Ph.D.’s for basic research grants and physicians only for trials. It is a challenge to be a successful physician researcher because you have the demands of patient care on the clinical side, but I’ve always enjoyed both aspects. I’ve been fortunate to have great collaborators that have allowed me to explore my research interests and still care for patients.”

What impact do you hope to make as President and CEO of Moffitt Center?

“We haven’t seen any significant rise in NIH funding for nearly a decade. That has been challenging for research institutions like the Moffitt Cancer Center. My responsibility is to make sure that the institution is financially solvent to pursue our mission of improving cancer care. One way we’re doing that is by partnering with insurers and the Center for Medicare and Medicaid Services as they explore new payment models. We’ve also partnered with pharmaceutical companies that have helped sponsor novel laboratory research.”

What is the future of the hematology field?

“In the past, we have been very linear in our view of science and biology. Research focused on gene mutations over the last ten years has been successful, but we know other factors also play significant roles in cancer. The disease is dynamic and complex, and it’s difficult to understand when we look at one part of the whole system.

“We’ll treat and prevent cancer better when we take a systems biology approach and look at the complete picture of how cancer affects the body, including metabolic and cell signaling networks. Systems biology is going to be critical in furthering our understanding of cancer’s complexities.

“At the same time, for many cancers, we’ve also been treating patients the same way for the past 40 years. If a therapy works, we give patients the highest dose that they can tolerate until it stops working. Then we move onto the next therapy, linearly. In the future, we’re going to see more adaptive therapeutic approaches that are flexible and can change in response to a patient’s tumor at a particular time.”

To learn how to nominate a colleague for the 2017 awards, visit the Celgene Awards for Clinical Research in Hematology website.

2017 Celgene Awards: Nominate a Colleague Today!

Although blood cancers are relatively rare, their root causes may not be so different from those of other cancers. And since blood cancer samples may be more easily accessible than solid tumor samples, it can help research efforts and make excellent models for research.

DR. LOUIS DEGENNARO, PRESIDENT AND CHIEF EXECUTIVE OFFICER OF THE LEUKEMIA & LYMPHOMA SOCIETY, EXPLAINS HOW ADVANCES IN BLOOD CANCER HAVE IMPROVED TREATMENT IN OTHER CANCERS.

DR. LOUIS DEGENNARO, PRESIDENT AND CHIEF EXECUTIVE OFFICER OF THE LEUKEMIA & LYMPHOMA SOCIETY, EXPLAINS HOW ADVANCES IN BLOOD CANCER HAVE IMPROVED TREATMENT IN OTHER CANCERS.

“We’re able to make faster progress in blood cancer because we’re studying the real cancer in the patient,” said Louis DeGennaro, president and CEO of the Leukemia & Lymphoma Society. “When you draw a leukemia patient’s blood sample, you have an exact representation of their cancer. That’s not the case in solid tumors, where you’d have to manipulate and grow the cells in a lab to study them.”

That’s why the LLS is especially focused during Blood Cancer Awareness Month on raising awareness of this second leading cause of cancer death in the United States (behind only lung cancer).

Blood cancer is actually a family of over 140 distinct diseases that affect blood cells, acting as “bullies” within the circulatory and immune systems. These abnormal blood cancer cells typically grow more quickly and survive longer than normal, interfering with the production and functioning of healthy cells.

Like all families, though, blood cancers have their differences. Lymphoma, leukemia, multiple myeloma and myelodysplastic syndromes (MDS), four major types of blood disorders, affect specific cell types in particular neighborhoods of the body. For instance, lymphoma alters white blood cells in the lymphatic system, while multiple myeloma disturbs plasma cells in the bone marrow.

These four diseases branch out into further subtypes. Leukemia comprises acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myeloid leukemia (CML) and chronic lymphocytic leukemia (CLL); lymphoma includes over 60 different forms. The distinction between all those subtypes lies partly in the specific cell type impacted. But scientists are learning that commonalities are more critical than distinctions.

“When it comes to treating cancer, we’re beginning to understand that the kind of cell affected is not the most important aspect,” DeGennaro said. “It’s the underlying mutations and mechanisms—which are shared by many types of cancer—that matter more.”

For instance, researchers have found mutations in a tumor-suppressor gene called TET2 in multiple blood cancers, suggesting it plays a role in how blood cells are regulated in the body. But even beyond blood cancer, the TET gene family has also been linked to breast, liver, lung, pancreatic and prostate cancers.

Blood Cancer's Family Tree

Their commonalities may mean medical advances in one blood cancer could provide insights into others.

An example is a class of therapies called tyrosine kinase inhibitors (TKIs), which have nearly doubled the five-year survival rate for CML since they were introduced 15 years ago. Today, TKIs have been approved to treat many other diseases, including lung, thyroid, kidney and breast cancers.

Roots of Care: Multiple Myeloma

“Blood cancer research is paying dividends to other cancers and diseases, and that will only continue as we learn more about these diseases,” said DeGennaro.

To learn how you can help the Leukemia & Lymphoma Society in supporting blood cancer research, read “Why I’m Walking in Light The Night® This Year.”

Cancer survives and thrives by working around the body’s natural defenses and turning off the immune system’s roadblocks before it can attack the disease. One way tumor cells flourish is by using the programmed death-1 (PD-1) receptor and programmed death-ligand 1 (PD-L1) pathway to dampen the immune system. Innovative new therapies are now tackling this pathway in an attempt to slow the progression of certain tumors

PD-1 is a “checkpoint,” which immune cells use to determine whether they should attack an enemy, such as a tumor cell or a cell infected with a virus, or shut themselves down. Cancers, though, have found ways to manipulate PD-1. For example, they make high levels of its ligand, PD-L1. So when immune cells approach tumors, they become anesthetized by the PD-L1 and lose their ability to attack.

New immunotherapy research is examining whether antibodies that block the PD-1/PD-L1 pathway can awaken and reactivate immune cells so they can once again kill tumor cells.

PD-1 and PD-L1 antibodies release the brakes on the immune system and can restore its natural antitumor response

There are other therapies designed to work with the immune system to combat cancer, but PD-1 and PD-L1 inhibitors may hold unique potential for some hard-to-treat cancers.

“PD-1 and PD-L1 antibodies release the brakes on the immune system and can restore its natural antitumor response,” said Robert Hershberg, Executive Vice President, Head of Business Development and Global Alliances, at Celgene Corporation,former Chief Scientific Officer and leader of the Immuno-Oncology Center of Excellence. “I think there’s very little doubt now that the future of oncology is inextricably linked to the immune system.”

While targeted therapies effectively shut down just one target within cancer cells, immunotherapy has more widespread effects — working with the body’s immune system as a whole to make it more difficult for the cancer to survive. Early clinical research suggests that a range of solid tumor cancers, including melanoma, lung cancer, bladder cancer, head and neck cancer (among others), respond to immunotherapy. Using sophisticated immune monitoring techniques to determine which patients respond to these immune-targeting agents remains a crucial endeavor at Celgene.

Disrupting the PD-1 checkpoint may also result in an unchecked immune response that may lead to adverse effects for some patients. Researchers are learning how to engineer these therapies to not only be more effective but also minimize molecular interactions that may have undesirable consequences.

Down the road, combination therapy with PD-1 and PD-L1 antibodies could be even more advantageous. “It’s a breakthrough and revolutionary, but really the tip of the iceberg,” Hershberg said.

PETER SCHAFER, EXECUTIVE DIRECTOR OF TRANSLATIONAL MEDICINE AT CELGENE, BELIEVES WE ARE AT A TIPPING POINT WHERE THE COLLECTION OF LUPUS GENETIC RESEARCH IS ABOUT TO GIVE WAY TO NEW THERAPEUTIC APPROACHES.

PETER SCHAFER, EXECUTIVE DIRECTOR OF TRANSLATIONAL MEDICINE AT CELGENE, BELIEVES WE ARE AT A TIPPING POINT WHERE THE COLLECTION OF LUPUS GENETIC RESEARCH IS ABOUT TO GIVE WAY TO NEW THERAPEUTIC APPROACHES.

In the past 50 years, only one new therapy has been developed exclusively for lupus. Meanwhile, patients with this inflammatory disease — in which the body’s immune system attacks its own tissue — continue to combat symptoms like fatigue, joint pain and rashes.

But Peter Schafer, executive director of Translational Medicine at Celgene, believes new genetic research in lupus is finally giving way to new investigational approaches that target mutations driving the disease.

As this year’s Annual European Congress for Rheumatology (EULAR) 2017 gets underway in Madrid, Schafer explains how genetic research is opening up new avenues of research for this difficult-to-treat disease.

How is our growing understanding of the genetic changes underlying lupus influencing the development of new treatments options?

We’re living in an era that’s beyond the sequencing of the human genome. Over the past decade, researchers have identified a multitude of genetic variants linked with particular diseases. Companies are beginning to realize the value of targeting the proteins that are encoded by those genes.

Managing Lupus Remains a Challenge

How has our understanding of genetics evolved over the past decade?

Three years ago, if I told someone that there was a change in a part of a gene that did not include the “recipe” for a protein, they would dismiss that mutation. Now we know that you shouldn’t necessarily ignore it. We’re realizing that other parts of the gene may be doing something else—for instance, controlling the quantity of protein being produced. Sometimes, the most obvious experiments go undone. One example is comparing the amount of a protein being produced in people with a given disease and those without. You may never bother to look if you dismiss that genetic change.

Have researchers found such variants that are believed to contribute to lupus?

Yes. For instance, there are variants in the genes for two proteins, called Ikaros and Aiolos, that help with the development of the immune cells that can cause inflammation. Lupus patients have twice the normal Ikaros levels and four times the normal Aiolos levels.

“Until this year, there had not been a program to evaluate a treatment that is designed specifically to target the genetic drivers of lupus.”

Have therapies that target such mutations linked with lupus been developed?

A few medications exist that target some of the proteins of the identified genes, but they are not approved for treating lupus. Their use in lupus will have to be investigated. Until this year, there had not been a program to evaluate a treatment that is designed specifically to target these potential genetic drivers of lupus.

What makes developing targeted therapies for lupus more challenging than for diseases such as cancer?

Lupus can be a debilitating disease, but the mortality rate isn’t as high as in cancer. As a result, a patient is less likely to be willing to deal with side effects, and their expectation is much higher.

Also, you’re not trying to kill a tumor. Instead, you’re trying to maintain some degree of suppression of the immune system over the long term. Lupus patients don’t use a high dose of treatment for a short period and then stop; they have to keep using their therapy. You want to know how low the dose can be and still be effective, so you don’t put the patient at risk unnecessarily.

High Levels of Ikaros & Aiolos in Lupus

How challenging is it to test the efficacy of treatments for lupus?

Lupus affects so many different tissues, joints and organs. Clinical efficacy measures of a new lupus treatment should evaluate the effectiveness of that treatment across the various organ systems involved in lupus. You’re looking for an improvement in at least some of those symptoms without worsening others.

At this time, lupus patients are being classified by which tissues are affected. But now that we’re looking at the disease from a genetic perspective, we have seen genetic variants in lupus patients regardless of the tissue affected. This finding is shifting our thinking about how to approach a disease like lupus, because if all lupus cases have similar root causes, genetic evaluation is important. Classifying patients solely by their affected organs might not be as useful for treatment purposes.

To learn about how targeted therapies are being explored for other inflammatory diseases, read “Accelerating MS Research Through Teamwork, New Approaches.”