Dr. Brody on Second-Line CAR T-cell Therapy in DLBCL

Joshua Brody, MD, faculty member, Icahn Genomics Institute; director, Lymphoma and Immunotherapy Program, The Tisch Cancer Institute at Mount Sinai, discusses the significance of CAR T-cell therapies being used in earlier treatment lines in patients with diffuse large B-cell lymphoma (DLBCL) who relapse within their first year of receiving chemotherapy.

The previous standard of care for this patient population was additional lines of chemotherapy, even though these patients had experienced a quick relapse from first-line chemotherapy, Brody says. Now, however, CAR T-cell therapies such as axicabtagene ciloleucel (axi-cel; Yescarta) and lisocabtagene maraleucel (liso-cel; Breyanzi) can be administered in the second line after receiving FDA approval based on the findings from the phase 3 ZUMA-7 (NCT03391466) and TRANSFORM (NCT03575351) trials, respectively, Brody explains.

The benefits of CAR T-cell therapy are numerous; it is often a more effective approach than chemotherapy in DLBCL, with less overall adverse effects (AEs), Brody says. Particularly, delivering this treatment in the second line, as opposed to the third line or later, is associated with better outcomes, since patients are stronger from undergoing fewer prior therapies. Additionally, their T-cells are healthier and more likely to keep them in long-term remission, Brody notes.

Earlier-line CAR T-cell therapy also opens the door for more effective bridging therapies, as evidenced by the TRANSFORM study, which showed that bridging therapy is a debulking strategy that makes liso-cel perform better with less AEs, Brody says. As tumor bulk is the biggest predictor of AEs from CAR T-cells, the opportunity for bridging therapy is critical, Brody concludes.