What the Data Shows Regarding the Current Role in Therapy of Approved CAR T Products

Pharmacy Times interviewed Craig Freyer, PharmD, BCOP, a clinical pharmacy specialist at Penn Medicine in the University of Pennsylvania Health System, and Andrew Lin, PharmD, BCOP, an oncology pharmacy specialist at Memorial Sloan-Kettering Cancer Center, to discuss their presentation at the recent ATOPP 2021 summit on re-examining the why, who, and where of chimeric antigen receptor (CAR) T-cell therapy.

Alana Hippensteele: What has the data demonstrated regarding the current role in therapy for approved CAR-T products?

Craig Freyer: Yeah, Alana, so the data looks quite promising in a number of scenarios. I think if you look at the first FDA-approved indication for any CAR-T therapy, that being tisagenlecleucel for pediatric and young adults up to the age of 25 years in the relapse refractory setting, we see in a patient population that has poor 5-year overall survival and pretty limited responses to combination chemotherapy the complete remission and complete remission with incomplete count recovery rate exceeds 80%, and virtually all of those responses are minimal residual disease negative responses.

So, even in that study in patients that don't end up going to allogeneic stem cell transplant, we see deep and durable remissions in many patients. So, I think in the pediatric and young adult acute lymphoblastic leukemia (ALL) setting, the role of CAR-T cells for that younger population is well defined at this point in time in comparison to combination chemotherapy, although of course there is no head-to-head or randomized comparisons.

I think in the non-Hodgkin lymphoma setting, specifically in large cell lymphoma, I think we're learning more and more about the benefits of CAR-T therapy in that population. We have previous data from the SCHOLAR-1 study, which essentially was looking at what was at the time the standard of care combination chemotherapy for relapsed refractory large cell lymphoma.

We saw that responses were limited in that those responses oftentimes weren't durable. Of course, historically, we have sent these people to autologous stem cell transplant if they've had at least a partial response or even a complete response to salvage chemotherapy, but even in that scenario, many patients, especially high-risk patients, don't have long-term durable responses.

So, if you look at the role of CAR-T in the large cell lymphoma setting, the data with the ZUMA-1 study for axicabtagene ciloleucel, the JULIET study for tisagenlecleucel, and then the TRANSCEND-NHL-001 study for lisocabtagene maraleucel, you see response rates are quite good. Overall responses go from about 50% to 80%, and anywhere from about 40% to 55% of those people have complete responses.

We're getting longer follow-up for those patient populations to have a sense of the durability of response, but at 12 months we see that roughly half of those people are still in remission following CAR-T therapy. Again, we don't have any data comparing that directly to salvage chemotherapy with subsequent auto transplant, but from previous series of data in SCHOLAR-1, and also in other cohorts, these numbers do look favorable for the patient's long-term outcomes.