Improved outcomes with TKI maintenance after brexucabtagene autoleucel in Philadelphia chromosome ALL

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ABSTRACT: Brexucabtagene autoleucel (brexu-cel) produces high rates of measurable residual disease-negative (MRD-) complete response (CR) in adult patients with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL); however, subsequent relapses remain frequent. It is unclear whether maintenance with tyrosine kinase inhibitors (TKIs) can enhance remission durability. We evaluated outcomes among adult patients with relapsed/refractory Ph+ ALL who received commercial brexu-cel and achieved MRD- CR across 19 US institutions. Considering TKI maintenance as a time-varying covariate, we analyzed outcomes based on receipt of subsequent TKI maintenance vs no maintenance. Patients receiving consolidative transplantation or non-TKI maintenance were excluded. Fifty-one patients were included: 20 received TKI maintenance, and 31 received no maintenance. The use of TKI maintenance was associated with a significantly lower 1-year cumulative incidence of relapse (hazard ratio [HR], 0.12; 95% confidence interval [CI], 0.02-0.88; P = .037), which translated into improved progression-free survival (PFS; HR, 0.19; 95% CI, 0.04-0.85; P = .029) and a trend toward improved overall survival (HR, 0.34; 95% CI, 0.07-1.62; P = .18). There was no difference in nonrelapse mortality (HR, 0.83; 95% CI, 0.12-5.87; P = .85). This real-world analysis supports the administration of TKI maintenance in Ph+ ALL after achievement of MRD- CR with brexu-cel as a strategy to improve PFS after chimeric antigen receptor T-cell therapy.

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