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 chimeric antigen receptor T-cell therapy (CAR-T) for aggressive B-cell non-Hodgkin lymphoma (B-NHL) do not experience a durable remission. Several novel agents are approved to treat relapsed, refractory aggressive B-NHL; however, it remains unclear how to sequence these therapies pre- and post-CAR-T. We conducted a multicenter retrospective analysis to describe peri-CAR-T practice patterns and survival predictors for patients receiving CD19-directed CAR-T. Patients (n = 514) from 13 centers treated with CAR-T for B-NHL between 2015-2021 were included in the study. Survival curves were constructed using Kaplan-Meier method. Multivariate Cox regression analysis was used to determine the impact of the variables on survival outcomes. For all patients receiving CAR-T, a greater number of lines of therapy pre-CAR-T apheresis and bridging therapy were predictive of inferior progression-free survival (PFS) and overall survival (OS). The median PFS and OS from the time of CAR-T cell infusion were 7.6 and 25.6 months, respectively. From the time of progression post-CAR-T, the median OS was 5.5 months. The median PFS of treatments administered in the first-line post-CAR-T failure was 2.8 months. Patients with refractory disease on day 30 had inferior OS and were less likely to receive subsequent treatment(s) than other patients with CAR-T failure. Allogeneic hematopoietic cell transplantation for selected patients at any time following CAR-T failure led to durable responses in over half of patients at 1 year. These data provide a benchmark for future clinical trials in patients with post-CAR-T cell progression, which remains an unmet clinical need.

Graphical abstract

Figure 1.

Survival curves for all patients receiving CAR-T and patients with CAR-T failure. Survival curves constructed using the Kaplan-Meier method. All curves include 95% CI and censored points are denoted with a mark on the curve. (A) PFS of all patients receiving CD19-directed CAR-T for aggressive B-NHL, from the time of CAR-T infusion. (B) OS of all patients receiving CD19-directed CAR-T for aggressive B-NHL, from the time of CAR-T infusion. (C) OS of all patients with CAR-T failure from time of post–CAR-T progression. (D) PFS of patients with CAR-T failure in patients who received subsequent therapies for aggressive B-NHL, from time of CAR-T progression. (E) OS of patients with CAR-T failure stratified by those who received subsequent therapy post–CAR-T vs those who did not. (F) OS from time of progression post–CAR-T for patients with SD or progressive at day 30 vs all other patients experiencing progression post–CAR-T. CI, confidence intervals; SD, stable disease; Tx, treatment.

Figure 2.

Best response to first- and second-line treatment regimens given after CAR-T failure. Regimens are listed in order of descending response. To right of each regimen in the ORR% (CR%). Lenalidomide-based regimens were analyzed separately from tafasitamab + lenalidomide. Lenalidomide-based regimens included either lenalidomide alone (6) or lenalidomide plus the following: rituximab (6), rituximab + radiation (1), rituximab + steroids (1), rituximab + intrathecal chemotherapy (1), intrathecal chemotherapy (1), steroids (1), venetoclax (1), obinutuzumab (2), and obinutuzumab + venetoclax (4) (supplemental Table 6). Ab, antibody; BR, bendamustine + rituximab; No., number; n, number; PR, partial response.

Figure 3.

PFS of select bridging therapies and select first-line therapies after CAR-T failure. Median PFS is depicted to the right of each individual regimen. Ab, antibody; PolaBR, polatuzumab + bendamustine + rituximab.