Lisocabtagene Maraleucel in Relapsed/Refractory Mantle Cell Lymphoma (MCL): Primary Analysis of the MCL Cohort From TRANSCEND NHL 001, a Phase I Multicenter Seamless Design Study
Michael Wang, Tanya Siddiqi, Leo I. Gordon, Manali Kamdar, Matthew Lunning, Alexandre V. Hirayama, Jeremy S. Abramson, Jon Arnason, Nilanjan Ghosh, Amitkumar Mehta, Charalambos Andreadis, Scott R. Solomon, Ana Kostic, Christine Dehner, Ricardo Espinola, Lily Peng, Ken Ogasawara, Amy Chattin, Laurie Eliason, M. Lia Palomba- Cancer Research
- Oncology
PURPOSE
Report primary analysis results from the mantle cell lymphoma (MCL) cohort of the phase I seamless design TRANSCEND NHL 001 (NCT02631044) study.
PATIENTS AND METHODS
Patients with relapsed/refractory MCL after ≥2 lines of prior therapy, including Bruton tyrosine kinase inhibitor (BTKi), alkylating agent, and CD20-targeted agent, received lisocabtagene maraleucel (liso-cel) at a target dose level of 50×106 (DL1) or 100×106 (DL2) CAR+ T cells. Primary endpoints were adverse events, dose-limiting toxicities, and objective response rate (ORR) by independent review committee per Lugano criteria.
RESULTS
Of 104 leukapheresed patients, liso-cel was infused into 88. Median (range) number of prior lines of therapy was 3 (1‒11) with 30% receiving ≥5 prior lines of therapy, 73% of patients were aged ≥65 years, 69% had refractory disease, 53% had BTKi refractory disease, 23% had TP53 mutation, and 8% had secondary central nervous system lymphoma. Median (range) on-study follow-up was 16.1 months (0.4‒60.5). In the efficacy set (n=83; DL1+DL2), ORR was 83.1% (95% CI, 73.3%‒90.5%) and complete response (CR) rate was 72.3% (95% CI, 61.4%‒81.6%). Median duration of response was 15.7 months (95% CI, 6.2‒24.0) and progression-free survival was 15.3 months (95% CI, 6.6‒24.9). Most common grade ≥3 treatment-emergent adverse events were neutropenia (56%), anemia (37.5%) and thrombocytopenia (25%). Cytokine release syndrome (CRS) was reported in 61% of patients (grade 3/4, 1%; grade 5, 0), neurological events (NE) in 31% (grade 3/4, 9%; grade 5, 0), grade ≥3 infections in 15%, and prolonged cytopenia in 40%.
CONCLUSION
Liso-cel demonstrated high CR rate and deep, durable responses with low incidence of grade ≥3 CRS, NE, and infections in patients with heavily pretreated relapsed/refractory MCL, including those with high-risk, aggressive disease.