Phase 2 results of lisocabtagene maraleucel in Japanese patients with relapsed/refractory aggressive B-cell non-Hodgkin lymphoma

Abstract

The autologous anti-CD19 chimeric antigen receptor (CAR) T-cell product, lisocabtagene maraleucel (liso-cel), is administered at equal target doses of CD8⁺ and CD4⁺ CAR⁺ T cells. This analysis assessed safety and efficacy of liso-cel in Japanese patients with relapsed or refractory (R/R) aggressive large B-cell lymphoma (LBCL) in Cohort 3 of TRANSCEND WORLD (NCT03484702). Liso-cel (100 × 10⁶ total CAR⁺ T cells) was administered 2-7 days after lymphodepletion. The primary efficacy endpoint was objective response rate (ORR; Lugano 2014 criteria) assessed by an independent review committee. Fourteen patients were enrolled; 10 received liso-cel infusion (median time to liso-cel availability, 23 days) and were evaluable at data cutoff (median follow-up, 12.5 months). Grade ≥ 3 treatment-emergent adverse events were neutropenia (90%), leukopenia (80%), anemia (70%), and thrombocytopenia (70%). All-grade cytokine release syndrome (CRS) was observed in 50% of patients, though no grade ≥3 CRS events were reported. Grade 1 neurological events occurred in 1 patient but were resolved without any intervention. Prolonged cytopenia (grade ≥ 3 at day 29) was reported for 60% of patients. The ORR was 70%, and complete response rate was 50%. The median duration of response was 9.1 months (95% confidence interval [CI], 2.1-not reached), and overall survival was 14.7 months (95% CI, 1.7-not reached). One patient diagnosed with central nervous system involvement after screening but before liso-cel infusion, responded to liso-cel. Liso-cel demonstrated meaningful efficacy and a manageable safety profile in Japanese patients with R/R LBCL.

Keywords: Japanese patients; large B-cell lymphoma; lisocabtagene maraleucel; non-Hodgkin lymphoma; relapsed/refractory.

FIGURE 1

Patient flow. ^aLiso‐cel consists of equal target doses of CD8⁺ and CD4⁺ CAR⁺ T cells, each of which was required to meet quality specifications. Although CAR T cells could be manufactured for all but one patient, the product for two patients did not meet the specifications of liso‐cel (i.e., 1 of the CD8⁺ or CD4⁺ cell components did not meet one of the requirements to be considered liso‐cel). CAR, chimeric antigen receptor; LDC, lymphodepleting chemotherapy; liso‐cel, lisocabtagene maraleucel

FIGURE 2

Primary analysis of individual patient responses to liso‐cel over time. ^aThe first dot represents the actual assessment date on or around day 29. ^bOne patient was diagnosed with secondary CNS lymphoma after screening and achieved a CR as a best overall response and was alive at the last assessment. CNS, central nervous system; CR, complete response; IRC, independent review committee; liso‐cel, lisocabtagene maraleucel; PD, progressive disease; PR, partial response

FIGURE 3

Cellular expansion over time. AUC_0–28d, area under the curve from 0 to 28 days post‐infusion; C_max, maximum expansion; Q, quartile; t_max, time to C_max

FIGURE 4

B‐cell aplasia incidence. B‐cell aplasia, defined as CD19⁺ B cells <3% of peripheral blood lymphocytes. Baseline was defined as the last non‐missing measurement before liso‐cel infusion, unless otherwise specified.

FIGURE 5

Patient with secondary CNS lymphoma. (A) The patient received two cycles of high‐dose methotrexate to prevent rapid progression of the brain mass lesion, with a response of stable disease (pre‐infusion). (B) A computed tomography scan on day 5 showed decrease of the CNS lesion while peritumoral cerebral edema was observed. (C) To improve the cerebral edema, high‐dose steroids (dexamethasone 20 mg/day every 6 h for 2 days and tapered) were started. After the initiation of steroid, the patient's symptoms rapidly improved, and he achieved a complete metabolic response per investigator assessment on day 29. (D) The complete metabolic response persisted for 3 months after infusion (day 102). CNS, central nervous system.