Brexucabtagene autoleucel ( KTE-X19; Brexu-cel; Tecartus ) is an autologous anti-CD19 chimeric antigen receptor ( CAR ) T-cell therapy approved for the treatment of patients 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 Brexucabtagene autoleucel in patients with R/R MCL ( median follow-up: 12.3 months; 60 efficacy-evaluable patients; Wang et al. N Engl J Med 2020 ).
Updated outcomes with 2 years of additional follow-up were presented.
Adult patients ( greater than or equal to 18 years ) with R/R mantle cell lymphoma underwent leukapheresis and conditioning chemotherapy followed by a single infusion of Brexucabtagene autoleucel.
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 patients.
After 35.6 months median follow-up, the ORR ( CR + partial response [ PR ] ) 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 months ( 95% CI, 13.5-47.1 ), with 25 of 68 treated patients ( 37% ) still in ongoing response ( all CR ) at data cutoff.
Late relapse more than 24 months post-infusion was infrequent ( n = 3 ).
The medians for progression-free survival ( PFS ) and overall survival ( OS ) were 25.8 months ( 95% CI, 9.6-47.6 ) and 46.6 months ( 95% CI, 24.9-not estimable ), respectively.
Minimal residual disease was analyzed in 29 patients total; 24 of 29 were MRD-negative at months 1, and 15 of 19 with available data were MRD-negative at month 6.
At data cutoff, the medians for DOR, PFS, and OS in the 15 MRD-negative patients were all not reached, versus 6.1, 7.1, and 27.0 months, in the 4 MRD-positive patients, respectively.
MRD-negative status at months 1, 3, and 6 was associated with durable response, with 55%, 71%, and 69% of MRD-negative patients at those timepoints remaining in ongoing CR at data cutoff.
Circulating tumor DNA analysis of MRD at months 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 of interest occurred since the primary report.
The most frequent grade 3 or more adverse events was neutropenia ( 1 [ 1% ] grade 3; 7 [ 10% ] grade 4 ).
Two patiens had Brexucabtagene autoleucel-related grade 3 serious infections: pneumonia and upper respiratory tract infection ( n = 1 ); influenza ( n = 1 ).
There were no new cytokine release syndrome adverse events and 1 new serious neurologic adverse effect of grade 3 encephalopathy ( 13.0 months post-infusion ) that was considered not related to study treatment.
Three new grade 5 adverse effects occurred, none of which were considered related to study treatment: Salmonella bacteremia ( 24.9 months post-infusion ), myelodysplastic syndrome ( 25.2 months post-infusion ), and acute myeloid leukemia ( 37.5 months post-infusion ).
In conclusion, these data represent the longest follow-up of CAR T-cell therapy in patients with mantle cell lymphoma to date and suggest that Brexucabtagene autoleucel induces durable long-term responses with manageable safety and low late relapse potential in R/R mantle cell lymphoma. ( Xagena )
Wang M et al, J Clin Oncol 2022; ( 40 suppl 16; abstr 7518 )