Résumé
We report the primary analysis from the R/R (third-line or later) MZL cohort of TRANSCEND FL (NCT04245839), a global, phase 2, single-arm, multicohort study evaluating efficacy and safety of the CD19-directed CAR T cell therapy, liso-cel.
Eligible, consenting patients had R/R MZL and received ≥2 prior lines of systemic therapy, including a combination of an anti-CD20 antibody and an alkylating agent, or had relapsed disease after HSCT. Patients received liso-cel (100 × 106 CAR+ T cells) after lymphodepleting chemotherapy (LDC). Bridging therapy was allowed, but reconfirmation of measurable disease was needed before LDC. The primary endpoint of ORR per independent review committee by CT using Lugano 2014 criteria (null hypothesis [H0]: ≤50%) and key secondary endpoint of CR rate (H0: ≤5%) were tested hierarchically.
Of 77 leukapheresed patients, 67 (87%) received liso-cel (safety set), and 66 (86%) were efficacy evaluable. Median (range) age was 62 years (37‒81), 85% had Ann Arbor stage 3/4 disease, 36% had progression of disease ≤24 months of initiation of first-line immunochemotherapy, 39% had refractory disease, and 22% had bulky disease. MZL subtypes included nodal (48%), splenic (27%), and extranodal/mucosa-associated lymphoid tissue (25%). Median prior lines of therapy was three. Median on-study follow-up was 24.1 months. The primary endpoint of ORR was met at 95.5% (95% CI, 87.3‒99.1; 1-sided P < 0.0001). The secondary endpoint of CR rate was also met at 62.1% (95% CI, 49.3‒73.8; 1-sided P < 0.0001). Duration of response (DOR)/PFS/OS 24-month rates were 88.6%/85.7%/90.4%. Similar 24-month DOR rates were observed for CR/PR at 89.0%/89.1%. Cytokine release syndrome/neurological events occurred in 76% (grade 3, 4%; no grade 4‒5)/33% (grade 3, 4%; no grade 4‒5) of patients. Prolonged cytopenia (grade ≥3 on Day 29) occurred in 42% (anemia/neutropenia/thrombocytopenia, 9%/27%/25%). Two grade 5 treatment-emergent AEs occurred (1 T-cell lymphoma [TCL]; 1 neutropenic sepsis). Liso-cel transgene testing and integration site analysis suggested that the TCL was unrelated to liso-cel.
In patients with R/R MZL, liso-cel demonstrated deep and durable responses with high 24-month survival rates. With a manageable safety profile, liso-cel is a potential treatment option for patients with R/R MZL.
Celgene, a Bristol-Myers Squibb Company.