Improved Outcomes with TKI Maintenance Following Brexucabtagene Autoleucel in Philadelphia-chromosome ALL
Tamer Othman, Gregory W. Roloff, Katharine Miller, Amy Zhang, Katherine C. Sutherland, Rawan G. Faramand, LaQuisa C Hill, Ibrahim N. Muhsen, Nikeshan Jeyakumar, Abdullah Ladha, Joshua P Sasine, Chenyu Lin, Noam E. Kopmar, Stephanie B. Tsai, Timothy E. O'Connor, Talal Hilal, Melhem M. Solh, Caitlin Guzowski, Virginia Tan, Navneet S Majhail, Minoo Battiwalla, Shahbaz A. Malik, John Mathews, Paul J. Shaughnessy, Luke Mountjoy, Kaitlyn C. Dykes, Aaron C Logan, Marc S. Schwartz, Matthew P Connor, Jiasheng Wang, Sumithira Vasu, Muthu Kumaran, Rasmus T. Hoeg, Sean I Tracy, Fevzi Firat Yalniz, George Yaghmour, Vinod A. Pullarkat, Ryan D Cassaday, Jessica T. Leonard, Bijal D Shah, Noelle V Frey, Lori S Muffly, Ibrahim AldossBrexucabtagene-autoleucel (brexu-cel) produces high rates of measurable residual disease-negative (MRD-) complete response (CR) in adults 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 adults with relapsed/refractory Ph+ ALL who received commercial brexu-cel and achieved MRD- CR across 19 U.S. institutions. Considering TKI maintenance as a time-varying covariate, we analyzed outcomes based on receipt of subsequent TKI maintenance versus 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 (HR 0.12; 95% CI, 0.02-0.88; p=0.037) which translated into improved progression-free survival (PFS, HR 0.19; 95% CI, 0.04-0.85; p=0.029) and a trend towards improved overall survival (OS, HR 0.34; 95% CI, 0.07-1.62; p=0.18). There was no difference in non-relapse mortality (NRM, HR 0.83; 95% CI, 0.12-5.87; p=0.85). This real-world analysis supports the administration of TKI maintenance in Ph+ ALL following achievement of MRD- CR with brexu-cel as a strategy to improve PFS following chimeric antigen receptor T cell therapy.