Lisocabtagene maraleucel as second-line therapy for large B-cell lymphoma: primary analysis of the phase 3 TRANSFORM study

• Published in: Blood Vol. 141; no. 14; pp. 1675 - 1684
• Main Authors: Abramson, Jeremy S., Solomon, Scott R., Arnason, Jon, Johnston, Patrick B., Glass, Bertram, Bachanova, Veronika, Ibrahimi, Sami, Mielke, Stephan, Mutsaers, Pim, Hernandez-Ilizaliturri, Francisco, Izutsu, Koji, Morschhauser, Franck, Lunning, Matthew, Crotta, Alessandro, Montheard, Sandrine, Previtali, Alessandro, Ogasawara, Ken, Kamdar, Manali
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 06.04.2023; American Society of Hematology
• Series: BLOOD
• Subjects: Adult; Antigens, CD19 - therapeutic use; Antineoplastic Combined Chemotherapy Protocols; Hematopoietic Stem Cell Transplantation; Humans; Immunotherapy, Adoptive - adverse effects; Life Sciences; Lymphoma, Large B-Cell, Diffuse - drug therapy; Medicin och hälsovetenskap; Proportional Hazards Models; Transplantation, Autologous
• ISSN: 0006-4971; 1528-0020; 1528-0020
• DOI: 10.1182/blood.2022018730

•Liso-cel significantly improved EFS, CR rate, and PFS vs chemotherapy ± ASCT as a second-line treatment for LBCL.•Liso-cel was well tolerated as a second-line therapy, with low rates of any grade or severe cytokine release syndrome and neurological events. [Display omitted] This global phase 3 study compared lisocabtagene maraleucel (liso-cel) with a standard of care (SOC) as second-line therapy for primary refractory or early relapsed (≤12 months) large B-cell lymphoma (LBCL). Adults eligible for autologous stem cell transplantation (ASCT; N = 184) were randomly assigned in a 1:1 ratio to liso-cel (100 × 106 chimeric antigen receptor–positive T cells) or SOC (3 cycles of platinum-based immunochemotherapy followed by high-dose chemotherapy and ASCT in responders). The primary end point was event-free survival (EFS). In this primary analysis with a 17.5-month median follow-up, median EFS was not reached (NR) for liso-cel vs 2.4 months for SOC. Complete response (CR) rate was 74% for liso-cel vs 43% for SOC (P < .0001) and median progression-free survival (PFS) was NR for liso-cel vs 6.2 months for SOC (hazard ratio [HR] = 0.400; P < .0001). Median overall survival (OS) was NR for liso-cel vs 29.9 months for SOC (HR = 0.724; P = .0987). When adjusted for crossover from SOC to liso-cel, 18-month OS rates were 73% for liso-cel and 54% for SOC (HR = 0.415). Grade 3 cytokine release syndrome and neurological events occurred in 1% and 4% of patients in the liso-cel arm, respectively (no grade 4 or 5 events). These data show significant improvements in EFS, CR rate, and PFS for liso-cel compared with SOC and support liso-cel as a preferred second-line treatment compared with SOC in patients with primary refractory or early relapsed LBCL. This trial was registered at www.clinicaltrials.gov as #NCT03575351. Abramson and colleagues report on the primary analysis of the TRANSFORM study, a randomized trial of lisocabtagene maraleucel (liso-cel) following a cycle of bridging therapy (if needed) vs standard-of-care salvage chemotherapy and autologous transplantation in second-line therapy of patients with primary refractory or early relapse large B-cell lymphoma. Liso-cel significantly improves event-free survival as well as complete response rate and progression-free survival but not overall survival after a median of 18 months follow-up. These data establish liso-cel as a standard of care for these patients with a previous poor prognosis.