Because of the potential for significant side effects of CAR-T therapies, the FDA requires Risk Evaluation and Mitigation Strategies (REMS) programs. The Bezos Family Immunotherapy Clinic at the Seattle Cancer Care Alliance is one of those approved sites.
So far there are only two chimeric antigen receptor T-cell (CAR-T) therapies approved by the U.S. Food and Drug Administration (FDA). They are Novartis’ Kymriah (tisagenlecleucel) and Gilead Sciences’ Yescarta (axicabtagene ciloleucel). They have been approved for slightly different, but sometimes overlapping patient populations. In the case of Kymriah, it is approved for pediatric and young adult acute lymphocytic leukemia (ALL) and for recurring or relapsing (r/r) aggressive lymphomas. Yescarta is approved for similar aggressive lymphomas.
Because of the potential for significant side effects, primarily cytokine release syndrome and neurotoxicities, the FDA required both companies set up Risk Evaluation and Mitigation Strategies (REMS) programs, which ensure that hospitals and associated clinics that dispense the therapies are specially certified and have on-site access to treatments for those adverse effects.
The Bezos Family Immunotherapy Clinic at the Seattle Cancer Care Alliance is one of those approved sites. The SCCA and the Bezos Clinic are an alliance of specialists from the Fred Hutchinson Cancer Research Center, Seattle Children’s, and the University of Washington Medicine. Dr. David Maloney, medical director of the Bezos Family Immunotherapy Clinic and director of cellular immunotherapy at Fred Hutchinson Cancer Research Center took time out from treating patients and running clinical trials to talk to BioSpace.
Dr. David Maloney
Maloney says, “These types of therapies are totally different than any other cancer therapies. They are essentially living cells that actually replicate and grow in the patient as they attack the cancer. It’s exactly the opposite of chemotherapy, which goes in and causes damage, and the damage is slowly resolved over time. CAR-T cells are infused in a relatively small number of cells that actively grow as they engage the target tumors cells and kill them. It is a type of living therapy that can expand to eradicate all of the tumor.”
But the therapies are very new having only been approved in approximately the last year, and for some indications, in recent months. The REMS programs were set up because it requires experience to successfully treat and manage patients receiving the therapies. Maloney notes, “We have extensive experience with CAR-T therapy starting with clinical trials about four to five years ago. The clinic itself, the Bezos Family Immunotherapy Clinic, has been open for about a year-and-a-half, but before that, we were functioning within a transplant group. What you’ll find is the majority of the centers that have the expertise to deliver CAR-T cells came out of bone marrow transplant programs, because that’s the closest to the level of intensity to CAR-T therapies.”
Also, because CAR-T and other immunotherapies so far are unique to each patient, they respond differently. In other words, the clinics using these therapies to treat patients are still learning. Maloney says, “I think it’s a mistake to say they’re CD19 CAR-T cells. The constructs are different, meaning the genetic information used to modify the T-cells, the method of modifying those T-cells, is different. And in many ways the types modified and how they are grown are different. This results in differences in the product and to some degree the behavior of how patients react to them.”
And these differences not only affect the eventual outcomes for the patients, but healthcare systems’ resource utilization. For example, in some cases, immuno-oncology therapies are performed in-patient with mandatory one- to two-week hospital stays. Others can be conducted on an outpatient basis. But those decisions depend partially on the specific CAR-T therapy being used and partially on the individual patient. For example, Maloney says, “Because of that, Kymriah appears more user-friendly for the outpatient setting, rather than a mandatory hospitalization, which could be ultimately important in resource utilization in delivering the product. One of these two CAR-T therapies is the best for patients with r/r aggressive lymphoma.”
But, he notes, at this time there are more patients who would benefit from these therapies than the commercial companies can manufacture CAR-T cells for. And, to some extent, clinics to offer the services to patients.
There are companies working to develop a more generic, off-the-shelf CAR-T product, with Juno/Celgene leading the charge. Maloney says, “They have a very similar CD19 CAR that seems to differentiate itself. Its toxicity profile seems even more favorable to potentially do it as an outpatient administration.”
But time will tell, as that product hasn’t been approved yet, and one big problem with off-the-shelf CAR-T products is immune rejection.
However, Maloney notes, “This is a very exciting time for cancer immuno-therapy. The field is rapidly changing and each approval is another step in figuring out how to do this in a safer, more effective fashion.”
