Commercial anti‐CD19 CAR T cell therapy for patients with relapsed/refractory aggressive B cell lymphoma in a European center

Abstract

Two autologous anti-CD19 chimeric antigen receptors (CAR) T cells (axicabtagene ciloleucel [axi-cel] and tisagenlecleucel [tisa-cel]) are commercially approved in Europe for relapsed/refractory (R/R) diffuse large B cell lymphoma (DLBCL). We performed a retrospective study to evaluate patterns of use, efficacy and safety for axi-cel and tisa-cel. Data from 70 patients who underwent apheresis for commercial CAR T cells between January 2018 and November 2019 in our institution were retrospectively collected. Sixty-one patients were infused. The median age at infusion was 59 years old (range 27-75 years). The median number of prior therapies was 3 (range, 2-6). The overall response rates (ORRs) at 1 month and 3 months were 63% and 45%, respectively, with 48% and 39% achieving a complete response (CR), respectively. After a median follow-up after infusion of 5.7 months, the median progression-free survival (PFS) was 3.0 months (95% CI, 2.8-8.8 months), and the median overall survival (OS) was 11.8 months (95% CI, 6.0-12.6 months). In multivariate analysis, factors associated with poor PFS were the number of previous lines of treatment before CAR T cells (≥4) (P = .010) and a C reactive protein (CRP) value >30 mg/L at the time of lymphodepletion (P < .001). Likewise, the only factor associated with a shorter OS was CRP >30 mg/L (P = .009). Cytokine release syndrome (CRS) of any grade occurred in 85% of patients, including 8% of patients with CRS of grade 3 or higher. Immune cell-associated neurotoxicity syndrome (ICANS) of any grade occurred in 28% of patients, including 10% of patients with ICANS of grade 3 or higher. Regarding efficacy and safety, no significant difference was found between axi-cel and tisa-cel. This analysis describes one of the largest real-life cohorts of patients treated with axi-cel and tisa-cel for R/R aggressive B cell lymphoma in Europe.

Current Immunotherapy Approaches in Non-Hodgkin Lymphomas

“…Different grading criteria for CRS may also contribute, as the Penn grading system results in higher number of grade 3–4 CRS in comparison to Lee system [ 144 , 145 ]. Real-world data confirmed results of the pivotal studies in general patient populations [ 146 ]. Analyses focused on older fragile patients and patients with CNS involvement reported safety and efficacy also in these clinical situations [ 147 , 148 ].…”

First‐line treatment of double‐hit and triple‐hit lymphomas: Survival and tolerance data from a retrospective multicenter French study

“…There is also promising data with targeted therapies, such as BET inhibitors. Finally, despite the low numbers in this category, the results presented on CAR‐T cells are very encouraging for DHL and THL 17‐20 …”

The Association Between Glucocorticoid Administration and the Risk of Impaired Efficacy of Axicabtagene Ciloleucel Treatment: A Systematic Review

“…A total of four studies investigated the effects of glucocorticoids use on PFS (24)(25)(26)(27). Both Sesques et al and Nastoupil et al found no association between glucocorticoids use and PFS (24,27).…”

“…A total of four studies investigated the effects of glucocorticoids use on PFS (24)(25)(26)(27). Both Sesques et al and Nastoupil et al found no association between glucocorticoids use and PFS (24,27). Holtzman et al also assessed the effects of duration (P = 0.32), total dose (P = 0.59), average daily dose and initial high-dose pulsing of glucocorticoids on PFS, however, no specific cut-off value was provided (26).…”

“…As with PFS, the same four studies evaluated the impact of glucocorticoids on OS (24)(25)(26)(27). (25,26).…”