Selecting CAR T-Cell Therapy for Older Patients With Diffuse Large B-Cell Lymphoma

At the 2023 Lymphoma, Leukemia & Myeloma Congress in New York, New York, Jason Westin, MD, The University of Texas MD Anderson Cancer Center, Houston, Texas participated in a debate regarding choice of CAR T-cell therapy versus novel therapy for older adults with diffuse large B-cell lymphoma (DLBCL). 

Transcript:

Hi, I'm Dr Jason Westin from MD Anderson Cancer Center where I'm the Director of Lymphoma Clinical Research and the Section Chief for Aggressive Lymphomas. I'm here at the 2023 Lymphoma, Leukemia & Myeloma Conference in New York where we're talking about CAR T-cell therapy. And we had a nice debate today of CAR T-cell therapy versus novel therapy for older adults. 

We've recently seen a complete paradigm shift in this space for relapsed large B-cell lymphoma patients where CAR T-cells didn't exist, and then 6 or 7 years ago, they were approved by the FDA in the third-line, and then more recently, in 2022, they were approved for second-line, based upon 3 randomized phase 3 studies, 2 of which were positive showing that axi-cel and liso-cel were both superior to standard chemotherapy and autologous transplant.

That has resulted in a paradigm shift in our algorithm for how we manage these patients that have relapsed or refractory disease, relapsed within the first year after first-line treatment, where now we think that axi-cel or liso-cel are the preferred approach and that chemo or transplant should not be given to those patients as a curative intent therapy as outcomes were inferior.

We showed earlier this summer that actually axi-cel has a statistically significant improvement in overall survival compared to transplant, including in patients who received CAR T-cell [therapy] as a third-line therapy, still couldn't overcome the difficulties with refractory disease and second line axi-cel was a superior treatment. Now that's for patients who were intended for either transplant or CAR T-cell.

At this congress we were talking about older patients who sometimes might fall into that group of fit for aggressive therapies, but we've also seen recently 2 clinical trials looking at patients who were ineligible for transplant, but could receive CAR T-cell therapy, specifically the ALYCANTE study looking at axi-cel and the PILOT study looking at liso-cel. 

And what we saw in those 2 phase 2 studies is that CAR T-cells work; they're relatively safe, but patients can tolerate them even with comorbidities, with advanced age, with labs that are outside the parameters for generally what we'd experience for a clinical trial, and that response rates look pretty darn similar to what we've seen for patients who were in the previous CAR T-cell phase 3 studies, implying that that therapy is available, curative intent therapy is available to patients who historically would've been considered ineligible for stem cell transplant.

So in our new algorithm that we proposed, we're no longer asking, "Is my patient eligible for transplant? Yes or no?"

Now we're asking, "How long ago was first-line therapy?" And if it was within 1 year, which is the vast majority of patients, CAR T-cell is the way to go — even if that patient would not have been eligible for transplant in the past, which allows us to offer curative intent therapy to more and more of our patients, which is a wonderful thing.

Source: 

Westin J. Debate (CAR-T): Older Patients with Aggressive Lymphoma Should Receive CAR-T cells vs Novel Agents. Presented at Lymphoma, Leukemia & Myeloma Congress; October 18-21, 2023. New York, NY