Evolving Role of CAR T Cell Therapy in First- and Second-Line Treatment of Large B Cell Lymphoma

We review the recent practice-changing trials of anti-CD19 chimeric antigen receptor (CAR) T cell therapies in large B cell lymphoma (LBCL) including phase 3 comparisons with second-line standard-of-care (SOC) and phase 2 investigations in transplant-ineligible patients or as part of first-line treatment.

ZUMA-7 found significantly improved overall survival and event-free survival (EFS) with axicabtagene ciloleucel (axi-cel) versus SOC of salvage chemotherapy followed by autologous stem-cell transplantation. This represents the first such survival improvement in nearly 30 years for early-relapsed or refractory (r/r) LBCL. TRANSFORM demonstrated prolonged EFS for lisocabtagene maraleucel (liso-cel) versus SOC but BELINDA did not for tisagenlecleucel. Second-line CAR T cell was a viable curative-intent therapy in elderly (ZUMA-7; axi-cel) and/or transplant-ineligible (PILOT; liso-cel) patients. ZUMA-12 demonstrated effectiveness for axi-cel as part of first-line treatment for high-risk LBCL. These results support a role for CAR T cell therapy as new second-line SOC for r/r LBCL and highlight its potential evolution into future first-line treatment for high-risk disease.