Accurately Predicting CAR-T Toxicity Prior to Patient Treatment Could Help Expand Access to Care

Jason Westin, MD, FASCP

This is the second part of a Q&A with Jason Westin, MD, FASCP. For the first part, click here.

Although chimeric antigen receptor T-cell (CAR-T) therapies have had a transformative impact on the landscape of care for hematological malignancies like large B-cell lymphoma (LBCL), the toxicities that sometimes accompany treatment with these therapies often requires them to be administered in state-of-the-art facilities. As such, access to these treatments is not universally available to all patients, and socioeconomic factors impact access to care for CAR-T therapy.

Jason Westin, MD, FASCP, the director of the Lymphoma Clinical Research Program at University of Texas MD Anderson Cancer Center, presented updated data from the ZUMA-7 clinical trial (NCT03391466) evaluating the CAR-T axicabtagene ciloleucel (axi-cel, Yescarta; Kite Pharma) at the American Society of Clinical Oncology (ASCO) 2023 Annual Meeting, held June 2-6, in Chicago, Illinois. Although the presentation was primarily focused on a new overall survival analysis, it also included updated safety data.

Shortly after the end of the conference, CGTLive™ spoke with Westin about the new safety data he presented and how it compared to data seen in earlier literature on axi-cel. He also discussed the topic of CAR-T toxicities more broadly, how they impact access to care, and how predicting toxicity on an individual patient level prior to treatment could ensure that resources are allocated more effectively.

CGTLive: How do the data you presented at ASCO’s 2023 conference align with prior literature on axi-cel, and what insights do they offer in combination for clinicians?

Jason Westin, MD, FASCP: The results we presented at the ASCO meeting on axi-cel are similar and different to what we've seen before. They're similar in that the side effect profile did not appear to show any new signals. We know that cytokine release syndrome can be common, however, grade 3 or higher is very rare—and in fact, it was only 6% on the ZUMA-7 trial. We know that neurologic toxicities are common, but grade 3 or greater was around 20%, basically lining up with what we've seen from prior studies.

But what was new was that we had an update to the long-term outcomes of a few things, including hypogammaglobulinemia. That's something that's always a concern; it’s sort of an on-target effect from CAR T-cells, in that CD19-positive B-cells—not malignant ones, but benign B-cells—make antibodies, and the CAR T-cells are not so discriminatory as to what cell has CD19 expression: they will take care of B-cells that are benign as well as malignant. We saw hypogammaglobulinemia only in 11% of patients on the ZUMA-7 trial. Slightly higher than that got a little bit of treatment with intravenous immunoglobulin (IVIG), but it was a small minority of patients that had that. It is important to look out for late side effects, including infections, and in that update we presented at ASCO there were some infectious issues that were discussed, as in the New England Journal of Medicine paper. I would just highlight looking at the risk of pneumocystis, looking at the risk of zoster, and looking at the risk of hepatitis B reactivation. Those are all important things for treating physicians to be aware of in the post CAR T-cell setting. I think that those are the most important findings for what we've seen in the literature before versus what we've updated in this new dataset.

Do you think there is anything that can be done to help move towards a wider implementation of cell therapies in patient treatment, or anything that can be done to make these therapies more accessible?

CAR T-cells are an incredible breakthrough and they have helped take patients who potentially would have died of their cancer and put them into remission and effectively cured them of their disease—not everybody, and we still have more work to do to help more patients—but they have no doubt been a game-changer. But one of the limitations of CAR T-cells is their availability both in terms of geography and in terms of treatment setting. There are certain specialized centers that are able to deliver CAR T-cells mainly due to the management of potential toxicities. This is not a therapy that's available in [just] any practice because if things go wrong, they can go wrong in a hurry, and there is a need for inpatient management and potentially expert care. Having the ability to predict better which patients might have those toxicities and therefore extend those patients to specialized centers—and if patients are predicted not to have toxicities—that's something that potentially could allow more and more centers to treat those patients. But what I'd also say is that access to care is not just a geography thing, it's also related to the socioeconomic status of our patients. We've seen time and time again that certain demographics don't have as much access to specialized centers as others. Racial and ethnic minorities are often underrepresented in clinical trials and underrepresented at treatment centers that can deliver CAR T-cells. We need strategies to ensure that all of our patients have better access to these life-changing treatments.

Transcript edited for clarity.

Click here for more coverage of ASCO 2023.

REFERENCE
Westin J, Oluwole OO, Kersten MJ, et al. Primary overall survival analysis of the phase 3 randomized ZUMA‑7 study of axicabtagene ciloleucel versus standard‑of‑care therapy in relapsed/refractory large B-cell lymphoma. Presented at: the American Society of Clinical Oncology (ASCO) 2023 Annual Meeting, held June 2-6, in Chicago, Illinois. Abstract #LBA107