Outcomes with KTE-X19 in patients (pts) with relapsed/refractory (R/R) mantle cell lymphoma (MCL) in ZUMA-2 who had progression of disease within 24 months of diagnosis (POD24).

Abstract

7547 Background: KTE-X19 is an autologous anti-CD19 CAR T-cell therapy approved in the US and EU for the treatment of R/R MCL. In the ZUMA-2 study of KTE-X19 in R/R MCL, the objective response rate (ORR) at a median 17.5-mo follow-up was 92% (67% complete responses [CR]; Wang et al. ASH 2020 #1120). Here, we report results in pts with or w/o POD24, an indicator of poor outcomes (Visco et al. Br J Haematol 2019). Methods: Eligible pts with R/R MCL underwent leukapheresis and conditioning chemotherapy followed by a single infusion of KTE-X19. Efficacy results are reported for the 60 treated pts with ≥1 y of follow-up (median 17.5 mo); safety results are presented for all 68 treated pts. Results: High-risk disease characteristics were common in pts with (n=33) and w/o POD24 (n=35), although pts with POD24 had higher tumor burden and lactate dehydrogenase (LDH) levels, and more had blastoid type MCL (Table). ORR in pts with (n=28) and w/o POD24 (n=32) was 93% and 91%, with CR rates of 61% and 72%. In pts with and w/o POD24, median progression-free survival (PFS) was 11.3 mo (range, 0.9–30.3) and 29.3 mo (range, 0–35.9). Medians for duration of response (DOR) and overall survival (OS) were not reached in either group. Most common Grade ≥3 adverse events (AEs) in pts with vs w/o POD24 were neutropenia (91% vs 80%), thrombocytopenia (61% vs 46%), and anemia (55% vs 51%); Grade ≥3 cytokine release syndrome (CRS) and neurologic events occurred in 9% vs 20% and 27% vs 34%, respectively. There were no cases of Grade 5 CRS, KTE-X19–related secondary cancers, or replication-competent retrovirus in either group. In pts with vs w/o POD24, median peak CAR T-cell levels and median area under the curve were 53.4 cells/µL (range, 0.2–2566) and 583.4 cells/µL (range, 1.8–27,743.6) vs 112.4 cells/µL (range, 0.2–2589) and 1588.3 cells/µL (range, 3.8–27,238.7); by 12 mo, B cells were detectable in 8/11 (73%) vs 7/15 pts (47%) in ongoing response. Conclusions: KTE-X19 provided a high CR rate across all pts, with median DOR and OS not reached. Pts with POD24 had more aggressive high-risk disease characteristics (tumor burden, LDH levels, and blastoid MCL) and generally lower CAR T-cell expansion and PFS vs pts w/o POD24. Earlier intervention with CD19-directed CAR T-cell therapy may benefit pts with MCL with known high-risk factors. Clinical trial information: NCT02601313. [Table: see text]