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Second-Line CAR T-Cell Therapy for Relapsed/Refractory Large B-Cell Lymphoma
Patients with large B-cell lymphoma that is refractory to induction immunochemotherapy or relapses within one year after completion of induction have traditionally undergone a second-line reinduction treatment followed by high-dose chemotherapy and autologous stem cell transplantation (HDC/ASCT). However, only a minority of these patients achieve durable remission. In the industry-sponsored, multicenter, phase 3 TRANSFORM trial, researchers compared HDC/ASCT with the CD19-directed CAR T-cell lisocabtagene maraleucel (liso-cel) in patients with diffuse large B-cell lymphoma that progressed within 12 months of completion of initial therapy.
Patients aged 18 to 75 years underwent T-cell collection by leukapheresis prior to randomization to liso-cel or 3 cycles of investigator's choice of second-line immunochemotherapy followed by HDC/ASCT. One cycle of second-line immunochemotherapy was allowed in the liso-cel arm for patients with high tumor burden or rapid disease progression. Patients not responding to HDC/ASCT could cross over to liso-cel treatment.
Of 184 patients, 64% had diffuse large B-cell lymphoma (including transformed), 23% had high-grade B-cell lymphoma (including double-hit), and 9% had primary mediastinal B-cell lymphoma. With a median follow-up of 17.5 months, median event-free survival (EFS; the primary endpoint) was not reached with liso-cel and was 2.4 months with HDC/ASCT; 18-month EFS was 52.6% versus 20.8%, respectively. Higher complete response rates were achieved with liso-cel (74% vs. 43%; P<0.0001); 18-month progression-free survival was 58.2% versus 28.8%. Fifty-eight patients in the HDC/ASCT arm crossed over to receive liso-cel, with 53% achieving complete response. Grade 3 CAR T–related cytokine release syndrome occurred in 1% and neurologic events in 4% of patients in the liso-cel arm.
The TRANSFORM study further establishes CAR T-cell therapy as the preferred approach for primary refractory or early relapsed aggressive B-cell lymphomas. The similarly designed ZUMA-7 trial of axicabtagene ciloleucel also showed superiority to HDC/ASCT, although no benefit was observed in the BELINDA study of tisagenlecleucel, in which CAR T-cell administration occurred at a later time point (NEJM JW Oncol Hem Jan 26 2022). Of note, the results of these studies do not apply to patients with relapse more than 1 year from induction therapy, wherein HDC/ASCT can provide higher responses among chemosensitive individuals than obtained among those with earlier failed treatment.
Abramson JS et al.
Title: Lisocabtagene maraleucel as second-line therapy for large B-cell lymphoma: Primary analysis of the phase 3 TRANSFORM study.
Source: Blood 2023 Apr 6; [e-pub]. (Abstract/FREE Full Text)