The Evolution of Chimeric Antigen Receptor T Cell Therapy - Episode 2
David Maloney, MD, PhD: Hello, and thank you for joining us today. Adoptive cell therapy with genetically modified T cells has generated tremendous excitement, showing rapid and durable responses in patients who previously had very dismal outcomes and limited treatment options.
In this OncLive Peer Exchange® discussion, I am joined by a panel of experts in the field of chimeric antigen T-cell therapy. Together we will look at the newest data, including data from the ASH [American Society of Hematology] 2018 Annual Meeting, to shed light on how these therapies are evolving and how they will shape the treatment landscape during the next several years as we expand their availability to more patients.
I am Dr David Maloney, professor of medicine at the University of Washington, medical director of immunotherapy at Seattle Cancer Care Alliance, and Leonard and Norma Klorfine Endowed Chair for Clinical Research at the Fred Hutchinson Cancer Research Center in Seattle, Washington.
Participating today on our distinguished panel are Dr Nilanjan Ghosh, clinical associate professor of medicine at the University of North Carolina, Chapel Hill School of Medicine, chief of the Lymphoma Division in the Department of Hematologic Oncology and Blood Disorders, and associate director of Clinical Trials at the Levine Cancer Institute/Atrium Health in Charlotte, North Carolina; Dr Leo Gordon, Abby and John Friend Professor of Cancer Research and professor of medicine, codirector of the Hematologic Malignancies Program in the Division of Hematology/Oncology at the Feinberg School of Medicine, Robert H. Lurie Comprehensive Cancer Center of Northwestern University in Chicago, Illinois; Dr Matthew Lunning, assistant professor of internal medicine in the Division of Oncology and Hematology at the University of Nebraska Medical Center in Omaha, Nebraska; and Dr Michael Pulsipher, section head of Blood and Marrow Transplantation and professor of pediatrics at the Keck School of Medicine of the University of Southern California and Children’s Hospital, Los Angeles, California. Thank you so much for joining us. Let’s begin. First of all, I think we should provide a historic perspective on the outcomes of these patients who are traditionally eligible for transplant and potentially now eligible for these newer treatments. Dr Ghosh….
Nilanjan Ghosh, MD, PhD: With the frontline treatment of diffuse large B-cell lymphoma, a number of patients, maybe 60% to 70% of patients, could expect long-term remission with frontline chemoimmunotherapy. However, patients who are primary refractory and relapse after that will end up getting salvage therapies. For those patients who are chemosensitive to those salvage therapies and eligible for autologous transplant, that is the standard of care. Unfortunately, many patients relapse after transplant, and many patients actually never make it to transplant because they are chemo refractory. And that is a huge unmet need, and that is the population in whom retrospective studies have shown that the overall survival is very, very low, as low as 6 to 7 months. And new treatments are indicated in that setting.
David Maloney, MD, PhD: What data do we have about the outcomes of salvage therapies for this population?
Nilanjan Ghosh, MD, PhD: So the SCHOLAR-1 data, which were published by Michael Crump, MD, and colleagues, showed that the CR [complete response] rate was less than 10% and the overall survival was in the tune of 6 to 7 months. It turns out that the patients who continued to be refractory have worse outcomes than the patients who relapse, and that’s defined as a benchmark to compare it with subsequent therapies.
David Maloney, MD, PhD: So a typical standard would be to try to get to these patients who have primary refractory disease or first relapse with salvage chemotherapy. And if we can get them into a good remission and they’re transplant-eligible candidates, the standard would be to go on to a transplant.
Leo I. Gordon, MD, FACP: I think I’d agree with what’s been said. I think there’s a fine point there that we probably should focus on a little bit, and that is those patients who are chemotherapy sensitive. You can define that in a number of different ways. There are patients who are chemotherapy sensitive who may have a 50% or 51% response, and I think there are some investigators who might take those patients to transplant, but there are some, including our institution, who like to see patients either in complete remission or near complete remission before moving on to transplant. There is probably some variability around the country in who goes on to transplant.
Matthew Lunning, DO: I agree. I think the most difficult part of my clinic is when you see a patient post salvage therapy and they’re getting their PET [positron emission tomography] scan and you have a Deauville 4, and that Deauville 4 can show, to your point, good chemosensitivity. There might be 1 residual site of disease such that you could say, “OK, they had a significant debulking, but they’re still a Deauville 4.” Could I take them to a transplant and consider posttransplant radiation in that patient population and still attempt curative intent versus a different Deauville 4, where you haven’t seen much cytoreduction and the delta SUV [standardized uptake value] or the change in the SUV is really not that impressive? I think there are 2 different populations. But I agree with you: With those PET CRs, standard of care is still to try to take them to transplant.
Leo I. Gordon, MD, FACP: Right. And I think one of the questions about the data from the SCHOLAR-1 study is how it’s hard to tell exactly how many of those patients actually were in remission going into their transplant. Some might have been, and some actually might not have been. That has to weigh in a little bit on interpretation of the data, but I’d agree with what’s been said. The results of the SCHOLAR-1 study were eye-opening in many ways and really provided a basis or a rationale for use of newer treatments, and that’s where the whole idea of CARs comes in.
Matthew Lunning, DO: I agree. It basically signaled the alarm to the oncology community that this is a population that needs novel therapies, and CAR T cell, I think, is providing an avenue, at least for the research and now with approvals to really see whether we can increase the long-term disease-free survival in this population.
David Maloney, MD, PhD: I think these are excellent points. I also think it’s important to remember that the advent of rituximab combinations has improved the outcome, but it’s also worsened the risk when people relapse. So our outcomes with transplant are not as good as they used to be.
Nilanjan Ghosh, MD, PhD: And for the early-relapse patients before 1 year of their frontline chemoimmunotherapy, the outcomes appear to be worse than for the patients who relapse late.
Transcript Edited for Clarity