Inotuzumab

Since the first approval of tisagenlecleucel in 2017, pediatric and young adult patients with relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL) may receive this CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy. We report real-world data from the Center for International Blood and Marrow Transplant Research (>2.5 years of follow-up). As of May 4, 2022, 768 patients with B-ALL had received tisagenlecleucel. Patients ≥18 and <18 (including <3) years old were treated in first relapse (26.6% and 26.7% [<3 years old: 44.8%], respectively) or primary refractory disease (12.4% and 12.1% [<3 years old: 15.5%]) with 17.6% and 11.6% [< 3 years old: 13.8%] having high disease burden (≥50% bone marrow [BM] blasts) and 20.2% and 20.2% [<3 years old: 13.8%] having low disease burden (>0 to <5% BM blasts). Among patients with ≥12 months post-infusion follow-up (N=578; median follow-up 32.1 months), the best overall response of complete remission/complete remission with incomplete blood count recovery was 86.0%. Twelve-month relapse-free survival (RFS) and overall survival (OS) were 61.8% and 79.4%, while 24-month RFS and OS were 50.3% and 63.8%, respectively. Age (<18 years) and disease burden (<50% BM blasts) were associated with better outcomes. Prior inotuzumab therapy and KMT2A rearrangement were associated with worse outcomes. Older patients (≥18 years) experienced a higher rate of any-grade cytokine release syndrome (CRS) associated with higher disease burden prior to infusion. Any-grade CRS and neurotoxicity were lower in patients <3 years old. Extended follow-up continues to demonstrate high rates of RFS and favorable safety in this population.

Tisagenlecleucel (tisa-cel) and brexucabtagene autoleucel (brexu-cel) are approved CD19 chimeric antigen receptor T-cell therapy (CAR T) products for young adults (YA) with relapsed/refractory B-cell acute lymphoblastic leukemia. A distinct analysis of YAs receiving commercial CD19 CAR T has not been reported. Using retrospective data from the Pediatric Real-World CAR T Consortium and the Real-World Outcomes of CAR T in Adult ALL collaboration, we describe the efficacy and safety of tisa-cel and brexu-cel in 70 YAs (18-26 years; tisa-cel, n = 50; brexu-cel, n = 20). Cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS) were observed more frequently for brexu-cel vs tisa-cel (CRS, 85% vs 56%; ICANS, 40% vs 18%). Complete response rates were similar between products at 80% for brexu-cel and 88% for tisa-cel. Relapse-free survival (RFS) at 12 months was 46% for brexu-cel and 36% for tisa-cel. Durability of remission over 12 months was 61% for brexu-cel vs 41% for tisa-cel; 12-month overall survival (OS) for brexu-cel was 84% vs 68% for tisa-cel. In multivariate analysis, low disease burden was associated with improved OS, whereas inotuzumab before CAR T was associated with inferior outcomes. This study demonstrates comparable real-world efficacy among YAs receiving CD19 CAR T irrespective of CAR T construct; however, rates of toxicity seem higher with brexu-cel.