Three-year follow-up of outcomes with KTE-X19 in patients with relapsed/refractory mantle cell lymphoma in ZUMA-2

7518 Background: Brexucabtagene autoleucel (KTE-X19) is an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy approved for the treatment of patients (pts) with relapsed/refractory (R/R) mantle cell lymphoma (MCL). In ZUMA-2, a 93% objective response rate (ORR; 67% complete response [CR] rate) was reported with KTE-X19 in pts with R/R MCL (median follow-up: 12.3 mo; 60 efficacy-evaluable pts; Wang et al. N Engl J Med. 2020). Here, we present updated outcomes with 2 years of additional follow-up. Methods: Adult pts (≥18 years) with R/R MCL underwent leukapheresis and conditioning chemotherapy followed by a single infusion of KTE-X19. Minimal residual disease (MRD) was an exploratory endpoint (sensitivity 10-5) evaluated in peripheral blood using next-generation sequencing. Updated results are reported for all 68 treated pts. Results: After 35.6 mo median follow-up, the ORR (CR + partial response) was 91% (95% CI, 81.8-96.7), with a 68% CR rate (95% CI, 55.2-78.5). The median duration of response (DOR) was 28.2 mo (95% CI, 13.5-47.1), with 25 of 68 treated pts (37%) still in ongoing response (all CR) at data cutoff. Late relapse > 24 mo post-infusion was infrequent (n = 3). The medians for progression-free survival (PFS) and overall survival (OS) were 25.8 mo (95% CI, 9.6-47.6) and 46.6 mo (95% CI, 24.9-not estimable), respectively. MRD was analyzed in 29 pts total; 24 of 29 were MRD-negative at mo 1, and 15 of 19 with available data were MRD-negative at mo 6. At data cutoff, the medians for DOR, PFS, and OS in the 15 MRD-negative pts were all not reached, vs 6.1, 7.1, and 27.0 mo, in the 4 MRD-positive pts, respectively. MRD-negative status at mo 1, 3, and 6 was associated with durable response, with 55%, 71%, and 69% of MRD-negative pts at those timepoints remaining in ongoing CR at data cutoff. Circulating tumor DNA analysis of MRD at mo 3 and 6 was predictive of relapse (AUC 0.80 and 0.75, respectively). No new safety signals were observed. Only 3% of treatment-emergent adverse events (AEs) of interest occurred since the primary report. The most frequent Grade ≥3 AE was neutropenia (1 [1%] Grade 3; 7 [10%] Grade 4). Two pts had KTE-X19-related Grade 3 serious infections: pneumonia and upper respiratory tract infection (n = 1); influenza (n = 1). There were no new cytokine release syndrome AEs and 1 new serious neurologic AE of Grade 3 encephalopathy (13.0 mo post-infusion) that was considered not related to study treatment. Three new Grade 5 AEs occurred, none of which were considered related to study treatment: Salmonella bacteremia (24.9 mo post-infusion), myelodysplastic syndrome (25.2 mo post-infusion), and acute myeloid leukemia (37.5 mo post-infusion). Conclusions: These data represent the longest follow-up of CAR T-cell therapy in pts with MCL to date and suggest that KTE-X19 induces durable long-term responses with manageable safety and low late relapse potential in R/R MCL. Clinical trial information: NCT02601313

Real-world experience among patients with relapsed/refractory mantle cell lymphoma after Bruton tyrosine kinase inhibitor failure in Europe:The SCHOLAR-2 retrospective chart review study

Mantle cell lymphoma (MCL) after relapse is associated with poor prognosis. No standard of care exists and available evidence for treatments is limited, particularly in patients who fail Bruton tyrosine kinase inhibitor (BTKi) therapy. This multicentre retrospective chart review study, SCHOLAR-2, addresses this knowledge gap and reports on data collected from 240 patients with relapsed/refractory MCL in Europe who were treated with BTKi-based therapy between July 2012 and July 2018, and had experienced disease progression while on BTKi therapy or discontinued BTKi therapy due to intolerance. The median overall survival (OS) from initiation of first BTKi therapy was 14.6 months (95% confidence interval [CI] 11.6–20.0) in the overall cohort, 5.5 months (95% CI 3.9–8.2) in 91 patients without post-BTKi therapy, and 23.8 months (95% CI 18.9–30.1) in 149 patients who received post-BTKi therapy (excluding chimeric antigen receptor T-cell treatment). In the latter group, patients received a median of one (range, one to seven) line of post-BTKi therapy, with lenalidomide-containing regimens and bendamustine plus rituximab being the most frequently administered; the median OS from initiation of first post-BTKi therapy was 9.7 months (95% CI 6.3–12.7). These results provide a benchmark for survival in patients with R/R MCL receiving salvage therapy after BTKi failure.</p

Real-world experience among patients with relapsed/refractory mantle cell lymphoma after Bruton tyrosine kinase inhibitor failure in Europe : The SCHOLAR-2 retrospective chart review study

Mantle cell lymphoma (MCL) after relapse is associated with poor prognosis. No standard of care exists and available evidence for treatments is limited, particularly in patients who fail Bruton tyrosine kinase inhibitor (BTKi) therapy. This multicentre retrospective chart review study, SCHOLAR-2, addresses this knowledge gap and reports on data collected from 240 patients with relapsed/refractory MCL in Europe who were treated with BTKi-based therapy between July 2012 and July 2018, and had experienced disease progression while on BTKi therapy or discontinued BTKi therapy due to intolerance. The median overall survival (OS) from initiation of first BTKi therapy was 14.6 months (95% confidence interval [CI] 11.6–20.0) in the overall cohort, 5.5 months (95% CI 3.9–8.2) in 91 patients without post-BTKi therapy, and 23.8 months (95% CI 18.9–30.1) in 149 patients who received post-BTKi therapy (excluding chimeric antigen receptor T-cell treatment). In the latter group, patients received a median of one (range, one to seven) line of post-BTKi therapy, with lenalidomide-containing regimens and bendamustine plus rituximab being the most frequently administered; the median OS from initiation of first post-BTKi therapy was 9.7 months (95% CI 6.3–12.7). These results provide a benchmark for survival in patients with R/R MCL receiving salvage therapy after BTKi failure

Three-Year Follow-Up of KTE-X19 in Patients With Relapsed/Refractory Mantle Cell Lymphoma, Including High-Risk Subgroups, in the ZUMA-2 Study

PURPOSEBrexucabtagene autoleucel (KTE-X19) autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy is approved for the treatment of relapsed/refractory mantle cell lymphoma (MCL). Outcomes after a 3-year follow-up in the pivotal ZUMA-2 study of KTE-X19 in relapsed/refractory MCL are reported, including for subgroups by prior therapy (bendamustine and type of Bruton tyrosine kinase inhibitor [BTKi]) or high-risk characteristics.METHODSPatients with relapsed/refractory MCL (one to five prior therapies, including prior BTKi exposure) received a single infusion of KTE-X19 (2 × 106 CAR T cells/kg).RESULTSAfter a median follow-up of 35.6 months, the objective response rate among all 68 treated patients was 91% (95% CI, 81.8 to 96.7) with 68% complete responses (95% CI, 55.2 to 78.5); medians for duration of response, progression-free survival, and overall survival were 28.2 months (95% CI, 13.5 to 47.1), 25.8 months (95% CI, 9.6 to 47.6), and 46.6 months (95% CI, 24.9 to not estimable), respectively. Post hoc analyses showed that objective response rates and ongoing response rates were consistent among prespecified subgroups by prior BTKi exposure or high-risk characteristics. In an exploratory analysis, patients with prior bendamustine benefited from KTE-X19, but showed a trend toward attenuated T-cell functionality, with more impact of bendamustine given within 6 versus 12 months of leukapheresis. Late-onset toxicities were infrequent; only 3% of treatment-emergent adverse events of interest in ZUMA-2 occurred during this longer follow-up period. Translational assessments revealed associations with long-term benefits of KTE-X19 including high-peak CAR T-cell expansion in responders and the predictive value of minimal residual disease for relapse.CONCLUSIONThese data, representing the longest follow-up of CAR T-cell therapy in patients with MCL to date, suggest that KTE-X19 induced durable long-term responses with manageable safety in patients with relapsed/refractory MCL and may also benefit those with high-risk characteristics

Three-Year Follow-Up of KTE-X19 in Patients With Relapsed/Refractory Mantle Cell Lymphoma, Including High-Risk Subgroups, in the ZUMA-2 Study.

PURPOSE: Brexucabtagene autoleucel (KTE-X19) autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy is approved for the treatment of relapsed/refractory mantle cell lymphoma (MCL). Outcomes after a 3-year follow-up in the pivotal ZUMA-2 study of KTE-X19 in relapsed/refractory MCL are reported, including for subgroups by prior therapy (bendamustine and type of Bruton tyrosine kinase inhibitor [BTKi]) or high-risk characteristics. METHODS: Patients with relapsed/refractory MCL (one to five prior therapies, including prior BTKi exposure) received a single infusion of KTE-X19 (2 × 10 RESULTS: After a median follow-up of 35.6 months, the objective response rate among all 68 treated patients was 91% (95% CI, 81.8 to 96.7) with 68% complete responses (95% CI, 55.2 to 78.5); medians for duration of response, progression-free survival, and overall survival were 28.2 months (95% CI, 13.5 to 47.1), 25.8 months (95% CI, 9.6 to 47.6), and 46.6 months (95% CI, 24.9 to not estimable), respectively. Post hoc analyses showed that objective response rates and ongoing response rates were consistent among prespecified subgroups by prior BTKi exposure or high-risk characteristics. In an exploratory analysis, patients with prior bendamustine benefited from KTE-X19, but showed a trend toward attenuated T-cell functionality, with more impact of bendamustine given within 6 versus 12 months of leukapheresis. Late-onset toxicities were infrequent; only 3% of treatment-emergent adverse events of interest in ZUMA-2 occurred during this longer follow-up period. Translational assessments revealed associations with long-term benefits of KTE-X19 including high-peak CAR T-cell expansion in responders and the predictive value of minimal residual disease for relapse. CONCLUSION: These data, representing the longest follow-up of CAR T-cell therapy in patients with MCL to date, suggest that KTE-X19 induced durable long-term responses with manageable safety in patients with relapsed/refractory MCL and may also benefit those with high-risk characteristics