Peri–CAR-T practice patterns and survival predictors for all CAR-T patients and post–CAR-T failure in aggressive B-NHL

Abstract

Most patients receiving CAR T-cell therapy (CAR-T) for aggressive B-cell lymphoma (B-NHL) will not experience a durable remission. There are several novel agents approved for the treatment relapsed, refractory aggressive B-NHL; however, it remains unclear how to sequence these therapies pre- and post-CAR-T (peri-CAR-T). We conducted a multicenter retrospective analysis for the purpose of describing peri-CAR-T practice patterns and survival predictors for patients receiving CD19-directed CAR-T. Patients (n=514) from thirteen centers treated with CAR-T for aggressive B-NHL between 2015-2021 were included. Clinical characteristics, CAR-T outcomes and treatment regimens administered pre- and post-CAR-T were collected. Survival curves were constructed using Kaplan Meier method. Multivariate Cox regression was used to determine the impact of variables on survival outcomes. For all patients receiving CAR-T, a greater number lines of therapy prior to CAR-T apheresis and receipt of bridging therapy were predictive of inferior progression-free survival (PFS) and overall survival (OS). From time of CAR-T infusion, median PFS and OS were 7.6 and 25.6 months (n=514). From time of progression post-CAR-T (n=254), median OS was 5.5 months. The median PFS of treatments given in the first-line post-CAR-T failure (n=167) was just 2.8 months. Patients with refractory disease at day 30 had inferior OS and were less likely to receive subsequent treatment(s) compared to other patients with CAR-T failure. AlloHCT for select patients at any time following CAR-T failure (n=16) led to durable responses in over half at one-year. These data provide a benchmark for future clinical trials in patients with progression post-CAR-T, an unmet clinical need.

How I treat refractory/relapsed diffuse large B‐cell lymphomas with CD19‐directed chimeric antigen receptor T cells

“…Early relapse under these circumstances is usually associated with a median OS of <6 months. [54][55][56][57] In a more recent study, the median OS for patients failing during Day 0-30 versus >Day 30 was 1.7 versus 3.0 months respectively. 58 In multivariate analysis, predictors of OS were high lactate dehydrogenase (LDH) at infusion, time to CAR T-cell failure <Day 30 and high C-reactive protein at infusion.…”

“…Nonetheless, data on safety, activity, and outcomes of allo-HSCT after CAR T-cell therapy are still limited. 56,57,59,73,89 In a recent multicentre retrospective study, 57 88 patients with R/R DLBCL (median age 54 years) received an allo-HSCT after anti-CD19 CAR Tcell therapy failure. The median (range) time between CAR T-cell therapy and allo-HSCT was 255 (63-753) days.…”

“…The second issue raised by the case is the best therapeutic option for a young patient with R/R DLBCL relapsing early after anti‐CD19 CAR T‐cell failure. Early relapse under these circumstances is usually associated with a median OS of <6 months 54–57 . In a more recent study, the median OS for patients failing during Day 0–30 versus >Day 30 was 1.7 versus 3.0 months respectively 58 .…”

“…Thus, allo‐HSCT represents a potential salvage therapy for R/R DLBCL relapsing after CAR T‐cell therapy. Nonetheless, data on safety, activity, and outcomes of allo‐HSCT after CAR T‐cell therapy are still limited 56,57,59,73,89 . In a recent multicentre retrospective study, 57 88 patients with R/R DLBCL (median age 54 years) received an allo‐HSCT after anti‐CD19 CAR T‐cell therapy failure.…”

Relapsed or refractory large B‐cell lymphoma after chimeric antigen receptor T‐cell therapy: Current challenges and therapeutic options

“…This analysis also concluded that early relapse was associated with poorer outcomes. 15 In summary, those that have PD after CAR-T therapy have a dismal prognosis, especially those who progress early.…”