KEY TAKEAWAYS
- The TRANSCEND NHL 001 study evaluated liso-cel in pts with R/R NHL.
- The study included pts with PET-positive R/R MCL after ≥2 lines of prior therapy.
- Liso-cel showed high ORR and CR, proving to be a promising treatment option for pts with high-risk, aggressive R/R MCL.
The study evaluated the effectiveness of liso-cel in patients with PET-positive R/R MCL who had received at least two prior therapies, including a BTK inhibitor, an alkylating agent, and a CD20-targeted agent. Patients were given liso-cel at either a target dose level of 50 (DL1) or 100 × 106 CAR+ T cells (DL2) following lymphodepleting chemotherapy (LDC).
The primary endpoints for the study were treatment-emergent AEs (TEAEs) and ORR by IRC using Lugano 2014 criteria. Secondary endpoints were CR rate, DOR, PFS, and OS. Primary (null hypothesis [H0]: ORR ≤40%) and key secondary (H0: CR rate ≤18%) efficacy hypothesis testing was hierarchical and established on the primary analysis set (PAS) of pts treated at DL2 with PET-positive disease per IRC at baseline, before LDC and after bridging therapy. All patients who received liso-cel (DL1 + DL2) were included in the safety set, while the efficacy set comprised patients with PET-positive disease per IRC at baseline (DL1 + DL2).
Of 104 patients who underwent leukapheresis, 88 received liso-cel (safety set; DL1, n = 6; DL2, n = 82). The median age of the patients was 68.5 years, ranging from 36 to 86 years. The median number of prior systemic lines of therapy was 3, ranging from 1 to 11. Of the patients, 69% had refractory disease, 53% were BTKi refractory, 33% had undergone prior HSCT, 75% had Ki67 levels of 30% or higher, 31% had blastoid morphology, 23% had TP53 mutations, and 8% had active CNS disease. The median on-study follow-up was 16.1 months, ranging from 0.4 to 60.5 months.
The primary and key secondary endpoints were realized based on the PAS (n = 74; ORR, 86.5% [95% CI, 76.5–93.3], P < 0.0001; CR rate, 74.3% [95% CI, 62.8–83.8], P < 0.0001). The efficacy set (n = 83), had an ORR of 83.1% (95% CI, 73.3-90.5) and a CR rate of 72.3% (95% CI, 61.4-81.6).
The study documented durable responses with a median DOR of 15.7 months and a median PFS of 15.3 months. Six pts in ongoing CR succumbed to COVID-19. The analysis of DOR, PFS, and OS was conducted while censoring COVID-19 deaths. The safety set (n = 88), revealed that 86% of pts experienced gr ≥3 TEAEs, primarily cytopenias. Four gr 5 TEAEs were encountered, with 61% of any-grade CRS and 31% of NE. Gr ≥3 infections were observed in 15% of cases, and 40% had prolonged cytopenia. Cellular kinetics and B-cell aplasia data to come.
Liso-cel has high, durable ORR and CR rates, with low rates of gr ≥3 CRS, NE, and infections. It could be a viable treatment option for high-risk, aggressive R/R MCL.
Source: https://onlinelibrary.wiley.com/doi/10.1002/hon.3196_LBA3
Clinical Trial: https://classic.clinicaltrials.gov/ct2/show/NCT02631044
Wang, M., Siddiqi, T., Gordon, L. I., Kamdar, M., Lunning, M., Hirayama, A. V., Abramson, J. S., Arnason, J., Ghosh, N., Mehta, A., Andreadis, C., Solomon, S. R., Kostic, A., Dehner, C., Espinola, R., Peng, L., Ogasawara, K., Chattin, A., & Palomba, M. L. LISOCABTAGENE MARALEUCEL (LISO-CEL) IN R/R MCL: PRIMARY ANALYSIS RESULTS FROM THE MCL COHORT OF THE SINGLE-ARM, MULTICENTER, SEAMLESS DESIGN TRANSCEND NHL 001 STUDY. Hematological Oncology, 41, 875-877. https://doi.org/10.1002/hon.3196_LBA3
