Who Should Receive CAR T-Cell Therapy for DLBCL?

Craig Sauter, MD, Memorial Sloan Kettering Cancer Center, New York, NY, explains which patients should receive CAR T-cells for diffuse large B-cell lymphoma (DLBCL).

Transcript

My name is Craig Sauter. I'm the Clinical Director of Adult Bone Marrow Transplantation at Memorial Sloan Kettering Cancer Center. My talk today centers around who should receive CAR-modified T-cells, specifically for relapsed and refractory diffuse large B-cell lymphoma.

As of this date, there have been 2 products, FDA-approved, for the indication of relapsed/refractory diffuse large B-cell lymphoma with CAR-modified T-cells. The 2 products are tisagenlecleucel and axicabtagene ciloleucel. These were both approved after multicenter, phase 2 single-arm studies.

The general indication is for patients who have relapsed and refractory disease following at least 2 lines of chemotherapy. These data have suggested potential long-term curability in approximately 30% of patients, with longest follow-up with axicabtagene ciloleucel. The focus of my talk was who should actually receive this therapy.

First and foremost, I would suggest that patients that are FDA indicated should receive CAR-modified T-cell therapy with careful consideration toward tumor volume in terms of prognostic impact, as well as performance status for patients proceeding to CAR-modified T-cells. This has come out in real-world analyses with patients with poorer performance status, as well as larger tumor bulk appearing to do somewhat poorer.

Additionally, with approximately 80% of patients generating at least a partial remission or complete remission, a large fraction of those patients eventually progress following CAR-modified T-cells. For those patients, we have to consider early responders towards further consolidation methods, including potentially allogeneic stem cell transplant.

Lastly, there have been small cohort analyses looking at unique patient groups, including patients with secondary central nervous system lymphoma receiving this therapy with obvious concern of potentially increased neurotoxicity with this therapy, given that unique treatment-emergent, adverse event with CAR-modified T-cells.

Encouragingly, in these small cohort series, there appears to be signal of efficacy without significant increased toxicity. Of note, this is with predominantly the products with 4-1BB costimulatory ligand as a second signal for the CAR-modified T-cell with both tisagenlecleucel as well as liso-cel.