Real-world outcomes with tisagenlecleucel in aggressive B-cell lymphoma: subgroup analyses from the CIBMTR registry

Abstract

Background: Tisagenlecleucel, a CD19 chimeric antigen receptor T-cell therapy, is approved for adults with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) or high-grade B-cell lymphoma (HGBCL) after ≥2 lines of therapy. When used in real-world settings, tisagenlecleucel has shown similar efficacy and improved safety compared with previous clinical trials. However, long-term data on real-world outcomes are lacking.

Methods: Clinical data from a cohort of patients treated with tisagenlecleucel in a real-world setting were captured in the Center for International Blood and Marrow Transplant Research registry. The main clinical outcomes analysed included response rate, duration of response, survival, adverse events and clinicopathologic and treatment characteristics that may affect those outcomes.

Results: As of May 2022, 1159 patients with R/R DLBCL/HGBCL received tisagenlecleucel. The overall response rate was 59.5%, and the complete response rate was 44.5%. With a median follow-up of 23.2 months in the efficacy set (n=968), the 24 month rates of progression-free survival, ongoing response and overall survival were 28.4%, 52.6% and 43.6%, respectively. Grade ≥3 cytokine release syndrome and neurotoxicity were reported in 6% and 7.4% of patients, respectively. Patients with DLBCL (vs HGBCL), complete response before infusion, prior autologous or allogeneic haematopoietic stem cell transplant and lactate dehydrogenase (LDH) within normal limits experienced more favourable efficacy outcomes, and those with Eastern Cooperative Oncology Group performance status of ≥2, ≥3 prior lines of therapy, elevated LDH and fludarabine-based lymphodepleting chemotherapy experienced less favourable safety outcomes.

Conclusions: This real-world study of tisagenlecleucel for patients with R/R DLBCL/HGBCL shows consistent efficacy and better safety outcomes than the pivotal trial. This study also identifies baseline disease characteristics and prior or concurrent treatments that may affect clinical outcomes.Tisagenlecleucel, a CD19 chimeric antigen receptor T-cell therapy, is approved for adults with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) or high-grade B-cell lymphoma (HGBCL) after ≥2 lines of therapy. When used in real-world settings, tisagenlecleucel has shown similar efficacy and improved safety compared with previous clinical trials. However, long-term data on real-world outcomes are lacking.Clinical data from a cohort of patients treated with tisagenlecleucel in a real-world setting were captured in the Center for International Blood and Marrow Transplant Research registry. The main clinical outcomes analysed included response rate, duration of response, survival, adverse events, and clinicopathologic and treatment characteristics that may affect those outcomes.As of May 2022, 1159 patients with R/R DLBCL/HGBCL received tisagenlecleucel. The overall response rate was 59.5%, and the complete response rate was 44.5%. With a median follow-up of 23.2 months in the efficacy set (n=968), the 24 month rates of progression-free survival, ongoing response, and overall survival were 28.4%, 52.6%, and 43.6%, respectively. Grade ≥3 cytokine release syndrome and neurotoxicity were reported in 6% and 7.4% of patients, respectively. Patients with DLBCL (vs HGBCL), complete response before infusion, prior autologous or allogeneic haematopoietic stem cell transplant, and lactate dehydrogenase (LDH) within normal limits experienced more favourable efficacy outcomes, and those with Eastern Cooperative Oncology Group performance status ≥2, ≥3 prior lines of therapy, elevated LDH, and fludarabine-based lymphodepleting chemotherapy experienced less favourable safety outcomes.In conclusion, this real-world study of tisagenlecleucel for patients with R/R DLBCL/HGBCL shows consistent efficacy and better safety outcomes than the pivotal trial. This study also identifies baseline disease characteristics and prior or concurrent treatments that may affect clinical outcomes.

Keywords: B cell; Chimeric antigen receptor - CAR; Hematologic Malignancies; Immunotherapy; Lymphoma.

Figure 1. Real-world efficacy outcomes after tisagenlecleucel infusion. Kaplan–Meier estimates for (A) progression-free survival, (B) duration of response and (C) overall survival in the efficacy set. For PFS and DOR, eight patients in ongoing CR/PR were censored at the time of post-infusion consolidative haematopoietic stem cell transplantation (HSCT); for OS, patients were not censored at the time of post-infusion HSCT. For DOR, time is relative to the onset of the first remission, 1 month=30.4 days. For PFS and OS, time is relative to the first infusion, 1 month=30.4 days. Nominal P values are reported and calculated by using the log-rank test to compare the best overall response (BOR) of CR vs BOR of PR. P values are not adjusted for multiplicity. CR, complete response; NE, not estimable; PR, partial response.

Figure 2. Effects of patient demographics and disease characteristics on efficacy and safety outcomes after tisagenlecleucel infusion. Multivariable analyses of patient demographics and disease characteristics on (A) efficacy outcomes in the efficacy set and (B) safety outcomes in the safety set with tisagenlecleucel. Multivariable logistic regression model estimates are presented for ORR, any cytokine release syndrome (CRS), CRS grade of ≥3, any immune effector-cell-associated neurotoxicity syndrome (ICANS) and ICANS grade ≥3; multivariable Cox regression model estimates are presented for DOR, OS and PFS. CRS and ICANS were graded according to the American Society for Transplantation and Cellular Therapy criteria and were based on the maximum grade that occurred within 100 days of tisagenlecleucel infusion. For each comorbidity group, ‘No’ indicates the absence of the specific comorbidity of interest. ^a71/968 (7.3%) patients were in CR at the time of infusion in the efficacy evaluable set. ^b73/990 (7.4%) patients were in CR at the time of infusion in the safety evaluable set. CR, complete response; DLBCL, diffuse large B-cell lymphoma; DOR, duration of response; ECOG, Eastern Cooperative Oncology Group; HGBCL, high grade B-cell lymphoma; HSCT, haematopoietic stem cell transplantation; IPI, International Prognostic Index; LD, lymphodepleting; LDH, lactate dehydrogenase; ORR, overall response rate; OS, overall survival; PFS, progression-free survival.