Navneet S. Majhail

Brexucabtagene-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.

In a real-world analysis of brexucabtagene autoleucel recipients with relapsed/refractory B-cell acute lymphoblastic leukemia (N = 278), lack of response to prior blinatumomab correlates with significantly worse following chimeric antigen receptor T-cell therapy outcomes.

Chimeric antigen receptor T-cell (CAR-T) therapies are standard of care for the treatment of several hematologic malignancies. Although patients receiving CAR-T therapies are frequently hospitalized given risks of cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS), there is increasing interest and evidence for the safety of their outpatient administration. We review various models of care and provide operational considerations for centers that are interested in developing outpatient CAR-T programs, with a particular emphasis on using remote patient monitoring (RPM) to facilitate outpatient care. Safe and high-quality outpatient care requires involvement of a multidisciplinary team with clinical pathways for rapid triage and evaluation for CRS and ICANS and their management and, if necessary, timely transition of patients to a higher level of acute care. RPM can facilitate scaling an outpatient program in a cost-effective manner, especially across multiple sites of care, and can reduce the time patients spend in an acute care setting. Overall minimizing hospital-based care and an outpatient approach can alleviate capacity challenges treatment centers have faced that have partly impacted access to CAR-T therapies and have the potential to positively impact patient and caregiver experience and quality of life.

Brexucabtagene autoleucel (brexu-cel) is a chimeric antigen receptor T (CAR T) cell therapy approved for adults with relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). We studied the impact of social determinants of health (SDoH) on outcomes of adults with B-ALL receiving brexu-cel. This retrospective analysis included adults (≥18 years) with R/R B-ALL treated with brexu-cel between 2021 and 2023. Cox proportional hazards models evaluated the association of race, ethnicity, and SDoH with progression-free survival (PFS) and overall survival (OS). 189 patients received brexu-cel and 57% were male. 55% were non-Hispanic White, 30% Hispanic, 7% non-Hispanic Black, 6% Asian/Pacific Islander, and 2% other/unknown. 43% were referred from private/community-based practices and 35% lived 50 miles or greater from the CAR T center. Health insurance included public (47%) and private (41%). 31% had a high social deprivation index (SDI, 76–99th percentile). Black race was associated with worse OS (HR 3.48; 95% CI 1.01–12.03). There was no difference in PFS (HR 1.03, 95% CI 0.50–2.10) or OS (HR 1.43; 95% CI 0.56–3.65) in Hispanic patients. Outcomes appear independent of SDoH and SDoH did not impact OS. We observed comparable outcomes to non-Hispanic patients.