Real‐world evidence of tisagenlecleucel for the treatment of relapsed or refractory large B‐cell lymphoma

Abstract

Tisagenlecleucel (tisa‐cel) is a second‐generation autologous CD19‐targeted chimeric antigen receptor (CAR) T‐cell therapy approved for relapsed/refractory (R/R) large B‐cell lymphoma (LBCL). The approval was based on the results of phase II JULIET trial, with a best overall response rate (ORR) and complete response (CR) rate in infused patients of 52% and 40%, respectively. We report outcomes with tisa‐cel in the standard‐of‐care (SOC) setting for R/R LBCL. Data from all patients with R/R LBCL who underwent leukapheresis from December 2018 until June 2020 with the intent to receive SOC tisa‐cel were retrospectively collected at 10 Spanish institutions. Toxicities were graded according to ASTCT criteria and responses were assessed as per Lugano 2014 classification. Of 91 patients who underwent leukapheresis, 75 (82%) received tisa‐cel therapy. Grade 3 or higher cytokine release syndrome and neurotoxicity occurred in 5% and 1%, respectively; non‐relapse mortality was 4%. Among the infused patients, best ORR and CR were 60% and 32%, respectively, with a median duration of response of 8.9 months. With a median follow‐up of 14.1 months from CAR T‐cell infusion, median progression‐free survival and overall survival were 3 months and 10.7 months, respectively. At 12 months, patients in CR at first disease evaluation had a PFS of 87% and OS of 93%. Patients with an elevated lactate dehydrogenase showed a shorter PFS and OS on multivariate analysis. Treatment with tisa‐cel for patients with relapsed/refractory LBCL in a European SOC setting showed a manageable safety profile and durable complete responses.

Real World Evidence of CAR T-Cell Therapies for the Treatment of Relapsed/Refractory B-Cell Non-Hodgkin Lymphoma: A Monocentric Experience

“…All patients had at least a post 1-month disease evaluation. The median time from apheresis to infusion was similar to that report in both the JULIET trial [ 6 ] (48 days vs. 39 days) and the real-life experiences from European centers [ 11 , 12 , 14 ]. Likewise, most of our patients (80%) received bridging therapy.…”

“…Due to the lack of randomized trials and the use of stringent inclusion criteria in the pivotal clinical trials, evaluating the feasibility of these treatments in the “real world” setting becomes mandatory. In the last year, several national experiences have been reported, showing that treatment with axi-cel or tisa-cel is feasible, with similar safety and efficacy profile to the pivotal trial [ 8 , 9 , 10 , 11 , 12 , 13 , 14 ]. The Italian Medicines Agency (AIFA) approved both cellular therapies in 2019 (August 2019 for tisa-cel and November 2019 for axi-cel) for the treatment of patients with LBCL (including high-grade B-cell lymphoma, primary mediastinal B-cell lymphoma, and transformed follicular or marginal lymphoma) who failed two or more lines of systemic therapies.…”

Efficacy and Safety of CAR-T Cell Products Axicabtagene Ciloleucel, Tisagenlecleucel, and Lisocabtagene Maraleucel for the Treatment of Hematologic Malignancies: A Systematic Review and Meta-Analysis

“…Of note, conference abstracts published by several European registries indicated that patients with axi-cel and tisa-cel administration in the real-world setting showed poor responses, PFS, or OS, compared to the pivotal trial, while the adverse events were manageable and of similar intensity. Real-world data from institutions in Spain, Germany, France, and the United Kingdom showed that the ORR of patients receiving axi-cel and tisa-cel did not exceed 70%, and the CRR of patients except from France was approximately 30% (58)(59)(60)(61)(62). Similarly, the French and British institutions observed that patients were likely to have a higher frequency of rapid relapses and a shorter survival period than expected (58,59,62), Poorer outcomes may be related to greater proportion of patients with advanced stage, refractory to previous treatments, or multiple number of previous lines of treatment.…”

Prophylactic Tocilizumab Prior to Anti-CD19 CAR-T Cell Therapy for Non-Hodgkin Lymphoma

“…All grade and grade ≥ 3 CRS was observed in 45% and 4.5% of patients, respectively ( 28 ). A recent report from the Spanish GETH/GELTAMO groups of NHL patients treated with tisagenlecleucel with CRS graded according to the ASTCT criteria showed an overall incidence of CRS of 71% and 5% incidence of grade ≥ 3 CRS ( 29 ). The decreased incidence of severe CRS in these later studies can be considered to be secondary to more frequent and earlier use of tocilizumab and corticosteroids and increased experience with CAR-T cell therapies and toxicity management ( 30 ).…”

“…In addition, given the inclusion of patients with an investigational, locally manufactured product that was infused fresh, there are no current fully comparable cohorts among commercially available products. Comparisons with published data of CRS and ICANS outcomes should be interpreted with caution, as increased experience with management of these complications have led to improved outcomes ( 26 ) ( 29 , 30 ). As mentioned throughout this discussion, the toxicity profile of CAR-T cell products varies with target, co-stimulatory signal and disease setting, and different preventive strategies may prove effective and safer in specific settings.…”