CAR T-cell Therapy in Relapsed/Refractory Mantle Cell Lymphoma


A brief review of CAR T-cell therapy in relapsed/refractory mantle cell lymphoma as studied in the ZUMA-2 clinical trial of brexucabtagene autoleucel.


Bijal D. Shah, MD, MS: This is a perfect segue to CAR [chimeric antigen receptor] T-cell therapy. Caron, you were part of a real-world consortium data set looking at CAR T. Now, when CAR T was first studied on the ZUMA-2 clinical trial, it was for BTKi [Bruton tyrosine kinase inhibitor] intolerance or resistance. Where are we now?

Caron A. Jacobson, MD, MPH: Well, I think the first place we are is that the FDA actually approved a much broader label, so it’s any relapsed or refractory mantle cell lymphoma. I think it was a very forward-thinking approval because of all of the studies that are now incorporating BTK inhibitors in the frontline setting, you don’t want patients to have to have gone through 2 lines of therapy if all of the effective therapies are being given in the front line. Thus, I think that was very forward thinking.

It is available now for patients with any relapsed/refractory mantle cell lymphoma. The vast majority of patients in the real world, as we’ve seen from 2 different series, one from Europe and one from the United States, have seen a BTKi. But what’s very interesting is there were about 18% of patients in the US series, which was about 96 patients I think in total, who had not seen a prior BTKi, and their results following brexucabtagene autoleucel were identical to patients who had seen a BTKi. I think this is the big question, is prior exposure to a BTKi important for T-cell fitness and the T-cell product, and at least from this very small cohort, it suggests that maybe it is not as important as we might have thought.

I think the data from ZUMA-2 have been replicated in these real-world series. Just like we’ve seen in large cell lymphoma, it’s very consistent. The response rates are consistent, the CR [complete response] rates of nearly 70% are consistent, and so far, what we’re seeing in terms of the 1-year progression-free and overall survival are very consistent, and the toxicities are consistent. I think 70% of patients would not have been eligible for the pivotal clinical trials. So we can now apply these therapies to a broader population of patients: patients with renal failure, heart failure, lower blood cell counts and bone marrow dysfunction, and still see the same excellent results. They continue to be really transformative, I think, for our patients.

Bijal D. Shah, MD, MS: That’s incredible. Thank you.

Transcript edited for clarity.

Related Videos
Carrie L. Kitko, MD
Lori A. Leslie, MD
Jean L. Koff, MD, MS
Lori A. Leslie, MD
Changchun Deng, MD, PhD
Guenther Koehne, MD, PhD
Ibrahim Aldoss, MD
Andrew P. Jallouk, BS, MD, PhD, assistant professor, Vanderbilt University
Elias Jabbour, MD, professor, Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center
Ibrahim Aldoss, MD