Lisocabtagene Maraleucel in Relapsed/Refractory Mantle Cell Lymphoma: Primary Analysis of the Mantle Cell Lymphoma Cohort From TRANSCEND NHL 001, a Phase I Multicenter Seamless Design Study

Abstract

Purpose: To report the primary analysis results from the mantle cell lymphoma (MCL) cohort of the phase I seamless design TRANSCEND NHL 001 (ClinicalTrials.gov identifier: NCT02631044) study.

Methods: Patients with relapsed/refractory (R/R) MCL after ≥two lines of previous therapy, including a Bruton tyrosine kinase inhibitor (BTKi), an alkylating agent, and a CD20-targeted agent, received lisocabtagene maraleucel (liso-cel) at a target dose level (DL) of 50 × 10⁶ (DL1) or 100 × 10⁶ (DL2) chimeric antigen receptor-positive T cells. Primary end points were adverse events (AEs), 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 previous lines of therapy was three (1-11) with 30% receiving ≥five previous lines of therapy, 73% of patients were age 65 years and older, 69% had refractory disease, 53% had BTKi refractory disease, 23% had TP53 mutation, and 8% had secondary CNS 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 to 90.5) and complete response (CR) rate was 72.3% (95% CI, 61.4 to 81.6). Median duration of response was 15.7 months (95% CI, 6.2 to 24.0) and progression-free survival was 15.3 months (95% CI, 6.6 to 24.9). Most common grade ≥3 treatment-emergent AEs 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), neurologic events (NEs) 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 R/R MCL, including those with high-risk, aggressive disease.

Fig 1.

Patient disposition and analysis sets (CONSORT). ^aNonconforming product was manufactured for 2 patients who did not receive CAR T cells due to death (n=1) and no longer meeting eligibility criteria (n=1). ^bSeven patients died because of disease progression, 1 because of an AE, and 1 because of other reasons (sepsis and pneumonia). ^cOne patient was ineligible due to second primary malignancy before LDC and 2 patients remained in ongoing CR after receipt of bridging therapy. ^dDefined as any product wherein one of the CD8 or CD4 cell components did not meet one of the requirements to be considered liso-cel but was considered appropriate for infusion. AE, adverse event; BTKi, Bruton tyrosine kinase inhibitor; CAR, chimeric antigen receptor; CR, complete response; DL, dose level; IRC, independent review committee; ITT, intent to treat; LDC, lymphodepleting chemotherapy; liso-cel, lisocabtagene maraleucel; PET, positron emission tomography.

Fig 2.

Forest plots of ORR (A) and CR rate (B) per IRC by prespecified subgroups (efficacy set). Response was evaluated by PET/computed tomography according to the Lugano 2014 criteria based on IRC assessment. ORR was defined as the proportion of patients who achieved a best response of CR or PR from the time of liso-cel infusion until disease progression, end of study, the start of another anticancer therapy, or HSCT. ORR and two-sided 95% exact Clopper-Pearson CI are shown in panel A. CR rate was defined as the proportion of patients who achieved a best response of CR from the time of liso-cel infusion until disease progression, end of study, the start of another anticancer therapy, or HSCT. CR rate and two-sided 95% exact Clopper-Pearson CI are shown in panel B. BTKi, Bruton tyrosine kinase inhibitor; CI, confidence interval; CNS, central nervous system; CR, complete response; HSCT, hematopoietic stem cell transplantation; IRC, independent review committee; LDH, lactate dehydrogenase; liso-cel, lisocabtagene maraleucel; ORR, objective response rate; PET, positron emission tomography; PR, partial response; sMIPI, simplified mantle cell lymphoma International Prognostic Index; SPD, sum of the product of perpendicular diameters; TP53, tumor protein 53.

Fig 2.

Forest plots of ORR (A) and CR rate (B) per IRC by prespecified subgroups (efficacy set). Response was evaluated by PET/computed tomography according to the Lugano 2014 criteria based on IRC assessment. ORR was defined as the proportion of patients who achieved a best response of CR or PR from the time of liso-cel infusion until disease progression, end of study, the start of another anticancer therapy, or HSCT. ORR and two-sided 95% exact Clopper-Pearson CI are shown in panel A. CR rate was defined as the proportion of patients who achieved a best response of CR from the time of liso-cel infusion until disease progression, end of study, the start of another anticancer therapy, or HSCT. CR rate and two-sided 95% exact Clopper-Pearson CI are shown in panel B. BTKi, Bruton tyrosine kinase inhibitor; CI, confidence interval; CNS, central nervous system; CR, complete response; HSCT, hematopoietic stem cell transplantation; IRC, independent review committee; LDH, lactate dehydrogenase; liso-cel, lisocabtagene maraleucel; ORR, objective response rate; PET, positron emission tomography; PR, partial response; sMIPI, simplified mantle cell lymphoma International Prognostic Index; SPD, sum of the product of perpendicular diameters; TP53, tumor protein 53.

Fig 3.

Kaplan-Meier curves of DOR (A), PFS (B), and OS (C) (efficacy set). ^aReverse Kaplan-Meier method was used to obtain median follow-up and its 95% CI. DOR was defined as the time from first response to progressive disease or death; PFS was defined as the time from liso-cel infusion to progressive disease or death; OS was defined as the time from liso-cel infusion to death. CI, confidence interval; DOR, duration of response; liso-cel, lisocabtagene maraleucel; OS, overall survival; PFS, progression-free survival.