Durable Efficacy and Manageable Safety in Patients Age ≥75 Years with Relapsed/Refractory Large B-Cell Lymphoma Treated with Tisagenlecleucel in the Real-World Setting

Background Tisagenlecleucel is approved for patients (pts) with relapsed/refractory large B-cell lymphoma (r/r LBCL) after ≥2 lines of prior therapy. Previous analysis of the Center for International Blood & Marrow Transplant Research (CIBMTR) registry showed high rates of durable responses, with similar outcomes among pts age ≥65 y vs pts age <65 y. Outcomes among pts age ≥75 y are limited. We report the first real-world analysis of outcomes in pts age ≥75 y with r/r LBCL treated with tisagenlecleucel. Methods Data were from a noninterventional, prospective, longitudinal study using the CIBMTR cellular therapy registry. Pts were treated in the US, Canada, or Israel. Efficacy analyses included ORR, CRR, PFS, and OS. Key safety outcomes included the incidence and severity of AEs, cytokine release syndrome (CRS), and immune effector cell-associated neurotoxicity syndrome (ICANS). Results As of May 4, 2023, 1375 pts had received tisagenlecleucel (infused set); 278 pts were age ≥75 y and had similar baseline characteristics as pts age <75 y (ECOG 0-1, 85% in both populations; elevated lactate dehydrogenase, 47% in both populations), received similar lymphodepleting regimens, and received tisagenlecleucel in a similar number of days post relapse (81 d vs 85 d, respectively). Pts age ≥75 y had a lower frequency of prior autologous hematopoietic cell transplantation than pts age <75 y (12% vs 26%, respectively; Fig.). In total, 121 pts age ≥75 y had comorbidities (121/278, 44%), including pulmonary (65/278, 23%), cardiac (60/278, 22%), and hepatic (21/278, 8%) disease. Among 247 pts age ≥75 y, 64% ORR (CR + PR; 95% CI, 58.1-70.3) and 47% CRR (95% CI, 41.0-53.8) were similar to 984 pts age <75 y 60% ORR (95% CI, 56.9-63.1), and 46% CRR (95% CI, 43.2-49.5). With a median follow-up (infusion to data cutoff) of 30 mo, 24-mo PFS in pts age ≥75 y was 23% (95% CI, 16.7-30.1) vs 28% in pts age <75 y (95% CI, 25.1-31.7). The 24-mo OS in pts age ≥75 y was 39% (95% CI, 31.2-47.2) vs 44% (95% CI, 40.1-47.8) in pts age <75 y (Fig.).AE frequency in pts age ≥75 y (n=250) was comparable with pts age <75 y (n=1004), including all-grade CRS (57% vs 60%, respectively; P=0.31) and grade 3/4 CRS (6% of each subgroup). Grade 5 CRS occurred in 2 pts age ≥75 y and 6 pts age <75 y. All-grade ICANS frequency in pts age ≥75 y was comparable with pts age <75 y (27% vs 22%, respectively; P=0.06). Grade 3/4 ICANS was reported by 7% of each subgroup; 4 pts age ≥75 y had grade 5 ICANS vs 1 pt age <75 y. Conclusions Tisagenlecleucel demonstrated similar efficacy and rates of CRS and ICANS in pts with r/r LBCL age ≥75 y as vs age <75 y. As few pts with r/r LBCL age ≥75 y received CAR-T cell therapy in clinical trials, real-world evidence for this age group is invaluable for guiding treatment decisions in this clinical setting, and supports consideration of tisagenlecleucel, a therapy that results in durable disease control in approximately one quarter of pts with a low risk of severe toxicity.