Efficacy and safety of tisagenlecleucel in Japanese adult patients with relapsed/refractory diffuse large B-cell lymphoma

Koji Kato,Koichi Akashi,Taizo Fujita,Shinichi Makita,Koji Izutsu,Takanori Teshima,Hideki Goto,Kota Tokushige

doi:10.1007/s10147-020-01699-6

Abstract

BackgroundTisagenlecleucel demonstrated a high rate of durable response in adult patients with relapsed/refractory (r/r) diffuse large B-cell lymphoma (DLBCL) in the pivotal global phase 2 JULIET study. Here, we report the efficacy and safety of tisagenlecleucel in the Japanese subgroup.MethodsJULIET (NCT02445248) is a single-arm, open-label, multicenter, phase 2 study involving adult patients with r/r DLBCL who either relapsed after or were ineligible for autologous stem cell transplant. Primary endpoint was best overall response rate (ORR; complete response [CR] + partial response [PR]) as judged by an independent review committee.ResultsIn Japan, of 17 patients enrolled, 9 were infused with tisagenlecleucel and completed ≥ 3 months of follow-up. Best ORR was 77.8% (7/9; 95% confidence interval, 40.0–97.2), with 5 patients (55.6%) in CR and 2 (22.2%) in PR. Cytokine release syndrome (CRS) occurred in 6 patients (66.7%), with grade 3 CRS in 2 patients (Penn grading scale). Two patients received tocilizumab. Two deaths (22.2%) occurred more than 30 days after tisagenlecleucel infusion due to disease progression, neither of which were related to tisagenlecleucel.ConclusionTisagenlecleucel showed a high best ORR with a manageable safety profile, thus offering a new treatment option in selected Japanese patients with r/r DLBCL.

Highlights

Diffuse large B-cell lymphoma (DLBCL) is an aggressive and the most common type of non-Hodgkin lymphoma (NHL) in Japan, with an incidence of 33% [1]
Of the 9 patients infused with tisagenlecleucel, 7 had relapsed disease and 2 had refractory disease at the start of the trial
The JULIET trial is a phase 2, multicenter, global, pivotal trial of tisagenlecleucel, a second-generation antiCD19 chimeric antigen receptor (CAR) T-cell therapy [6]. This subgroup analysis of JULIET assessed the efficacy, safety, and cellular kinetic profile of tisagenlecleucel in Japanese adult patients with r/r diffuse large B-cell lymphoma (DLBCL). This is the first report of an anti-CD19 CAR T-cell therapy in a Japanese subgroup to address the poor prognosis in this patient population

Summary

Introduction

Diffuse large B-cell lymphoma (DLBCL) is an aggressive and the most common type of non-Hodgkin lymphoma (NHL) in Japan, with an incidence of 33% [1]. Tisagenlecleucel is a second-generation anti-CD19 CAR T-cell utilizing 4-1BB as a co-stimulatory domain It targets CD19+ B cells and has shown efficacy against various subtypes of B-cell lymphomas, including DLBCL, in a singlecenter, phase 2a study [5]. A phase 2, multicenter, global, pivotal trial (JULIET; NCT02445248) was conducted, and tisagenlecleucel demonstrated a high rate. We report a subgroup analysis of the Japanese patients infused with tisagenlecleucel for r/r DLBCL in the JULIET trial. Tisagenlecleucel demonstrated a high rate of durable response in adult patients with relapsed/refractory (r/r) diffuse large B-cell lymphoma (DLBCL) in the pivotal global phase 2 JULIET study. Conclusion Tisagenlecleucel showed a high best ORR with a manageable safety profile, offering a new treatment option in selected Japanese patients with r/r DLBCL

Methods

Results

Conclusion