The U.S. Food and Drug Administration (FDA) today approved the CAR T-cell treatment axicabtagene ciloleucel (Yescarta®) for patients with follicular lymphoma (FL) that has returned or worsened despite earlier treatment. FL is the most common slow-growing non-Hodgkin’s lymphoma and while the disease can generally be managed, reoccurrence is common.
LLS was among the first to invest in CAR T in the 1990’s. Today, the therapy has rapidly become a mainstay of cancer care. LLS supported clinical trials that lead to the first FDA-approvals in 2017 of tisagenlecleucel (Kymriah) for relapsed or refractory childhood B-cell acute lymphoblastic leukemia and axicabtagene ciloleucel for a range of B-cell lymphomas. Funding was provided by LLS’s academic grant program to Dr. Carl June’s team at the University of Pennsylvania as well as the Therapy Acceleration Program® (TAP; our venture philanthropy arm) to Kite Pharma, a Gilead Company.
This is the first ever CAR T-therapy approved to treat a form of indolent non-Hodgkin lymphoma. FL, and indolent Hodgkin lymphomas in general, tend to grow and spread slowly at first, but they become more aggressive with each relapse. While there has been substantial improvement in long-term survival for these lymphomas, they are generally not curable and new treatment options are crucial for patients whose follicular lymphoma has not responded or has returned.
Today’s approval of was based on impressive results from ZUMA-5, a global Phase 2 study in adults. After a single infusion of axicabtagene ciloleucel, 94% of the participants had a measurable response to treatment and 80% had a complete response, meaning no cancer was detected at the median follow up time of nearly 1.5 years.
While all cancers are different, recently reported results among some of the first large B-cell lymphoma patients treated with axicabtagene ciloleucel show long-lasting benefit. Close to half of the 101 patients in the follow-up are still alive 4 years after a single axicabtagene ciloleucel infusion.
Years of experience with axicabtagene ciloleucel also means physicians have a clear picture of its short- and long-term safety. Like all CAR T therapies, axicabtagene ciloleucel can cause some serious side effects, including a transient over-activation of the immune system called cytokine release syndrome (CRS) as well as immune effector cell-associated neurotoxicity syndrome (ICANS). Although CRS and ICANS can be serious, they are signals that the CAR T-cells are working and as physicians have become more experienced with CAR T, they have learned how to recognize and treat it earlier.
LLS is looking to the future to bring the benefits of CAR T therapy to more cancer patients
CAR T-therapy has dramatically changed the outlook for patients with a range of B-cell lymphomas, as well as children and young adults with acute lymphoblastic leukemia. While LLS celebrates these successes, there is much more work to be done.
LLS has committed more than $90 million in investments to cellular immunotherapy for the treatment of blood cancers and our commitment is as strong as ever. Our current focus for CAR T-cell therapy is to make it available for more types of cancer and to make it less costly and quicker to administer. To speed the process and lower costs, LLS-funded researchers are working on “off the shelf” CAR T-therapies that use donor T cells instead of having to harvest and re-engineer each individual patient’s T-cells before reinfusing them. Beyond this approach, LLS is supporting the development of CARs with another type of immune cell, known as natural killer (NK) cells, which may have more powerful tumor-cell killing capacity.
Current CAR T-treatments work by targeting a protein called CD19, which plays a key role in B-cell lymphomas. We are funding research into other protein targets including BCMA, which plays a key role in multiple myeloma. There are two BCMA-targeting CAR T-therapies in review by FDA for the treatment of multiple myeloma. The FDA decision on one is due in the next few months and the other is due later this year.
I look forward to writing about these new and exciting therapies soon and to keeping you informed about our work on behalf of the more than 1.3 million Americans living with or in remission from blood cancer.
Amanda Monteiro is a leukemia mom, volunteer, and Children's Initiative Ambassador for The Leukemia & Lymphoma Society (LLS), advocate for pediatric cancer research and palliative care, graduate student of clinical social work, and mother to Eleanor on earth and Edie in heaven.
Today is International Childhood Cancer Day, a day that had little significance for me less than four short years ago. In October 2017, I heard the words, “your child has cancer,” which I soon learned could only be eclipsed by, “there is nothing more we can do.”
I gave birth to my first child, a happy and healthy baby girl, on July 30th, 2016. Edie was born eyes wide open with a fear of missing out that was unparalleled. She challenged and surprised, enchanted and delighted us with each milestone she achieved. She commanded audiences with her sparkling blue eyes and infectious smile. She was directive and willful beyond her earthly age. I relished every moment. For 14 months, I lived blissfully ignorant of what life had in store for our family.
Our “Meet the Researcher” series on The LLS Blog shares what our outstanding LLS-funded researchers are working on, the incredible impact they’re making in the fight against blood cancer, and what inspires their efforts to find better treatments and cures.
To commemorate Black History Month, LLS is highlighting exceptional clinicians and healthcare professionals throughout the month of February. Dr. Rayne Rouce is a physician at Texas Children's Cancer Center where she is a member of the Leukemia/Lymphoma/Bone Marrow Transplant/Stem Cell Transplant Program. Dr. Rouce is board certified in pediatrics and pediatric hematology/oncology by the American Board of Pediatrics.
What is your area of expertise and/or what is the focus of your research?
I am a pediatric oncologist and physician scientist, and spend the majority of my time working on new ways to use the immune system to target and kill blood cancers (called “immunotherapy”). Specifically, my scientist colleagues and I genetically modify T cells (immune cells) with artificial receptors trained to kill proteins on the surface of cancer. I am extremely fortunate because this area of research has grown exponentially over the past 10 years, allowing new and less toxic treatment options for patients who previously would have been told they had no additional treatment options.
How will blood cancer patients benefit from your work?
Blood cancer is where we have had the most success with immunotherapy. In fact, based on really remarkable results, patients with difficult-to-treat B-cell leukemia and lymphoma can receive CAR (chimeric antigen receptor) T cells commercially, meaning without having to enroll in an investigational protocol. Immunotherapy has revolutionized the treatment of relapsed B-cell leukemia and lymphoma, and we are now trying to extend this therapy to patients with other types of blood cancers. There are so many clinical trials, many of which are supported by The Leukemia & Lymphoma Society, that are testing immunotherapy treatments in patients with malignancies like non-Hodgkin lymphoma, acute myeloid leukemia (AML), T-cell lymphoblastic leukemia, and multiple myeloma. We are also working on developing immunotherapy treatments that can be made from healthy donors, thus immediately available to patients.
What inspired you to pursue a career in medicine?
I have always wanted to help people. I initially thought I wanted to be a psychiatrist, but once I did my first pediatric rotation in hematology/oncology, I immediately knew I had found my calling. What I love about my job is that I literally have the best of all worlds: I get to take care of patients and families during the most challenging times of their lives, and watch them overcome what seems like the impossible. On a daily basis, I’m surrounded by superheroes in the form of kids fighting cancer, and I get to work on finding new ways to safely kill cancer. I get to work with amazing doctors, nurses, scientists, and so many other healthcare workers and even organizations like LLS, with a common goal.
Why do you believe in the importance of diversity in healthcare?
Diversity in healthcare is key. Not only do we have a responsibility to provide culturally competent care to each and every patient we treat, we have a responsibility to ensure our healthcare teams mirror the diverse populations we serve. Diversity is not limited to race, ethnicity, and gender, but also extends to diversity of thought…diversity of experience. Enhancing diversity in healthcare won’t happen overnight, but small changes can result in huge impact on the pipeline of diverse students entering the healthcare profession. For example, in my role as Associate Director of Community Engagement at Baylor College of Medicine, we offer a number of programs for underrepresented minority K-12, undergrad, graduate, and post-grad students interested in healthcare careers.
How can the medical community and organizations engage more underrepresented groups?
There are a number of ways healthcare organizations can engage underrepresented groups! They can help raise awareness of diseases that disproportionately affect underrepresented groups, provide culturally competent education, and even partner with researchers/health professionals to enhance initiatives that benefit the pipeline of underrepresented healthcare workers.
In what capacity have you worked with LLS?
LLS has been an amazing constant throughout my training and career. I have worked as a junior investigator and investigator on LLS Specialized Center of Research grants, participated in community education initiatives hosted by LLS, including podcasts, blogs, and community forums, spoken at LLS Light the Night events, and been involved in countless other initiatives. LLS has been extremely supportive of my research, my patients/their families and my community advocacy efforts.
To learn more about how LLS is addressing diversity, equity, and inclusion across every aspect of our mission, please click here.