Efficacy and safety of blinatumomab: Post hoc pooled analysis in Asian adults with relapsed/refractory B-cell precursor acute lymphoblastic leukemia

Abstract

Background: Global studies have demonstrated the efficacy and safety of blinatumomab-a BiTE® (bispecific T-cell engager) targeted immuno-oncology therapy that mediates the lysis of cells expressing CD19 in patients with relapsed/refractory acute lymphoblastic leukemia (R/R ALL). Because limited data are available in Asian patients, we conducted a post hoc pooled analysis in 45 Asian adult patients with R/R ALL-19 from the blinatumomab arm of TOWER (NCT02013167) and 26 from Study 265, a phase 1b/2 study in Japanese adults (NCT02412306).

Methods: Patients received a maximum of two cycles of induction blinatumomab for 4 weeks by continuous intravenous infusion (cycle 1/week 1: 9 μg/day; cycle 1/weeks 2-4: 28 μg/day) followed by 2 weeks of no blinatumomab (each 6-week cycle); patients received 28 μg/day blinatumomab in subsequent cycles.

Results: Twenty of 45 patients enrolled (44%) achieved complete remission with full or partial hematologic recovery compared with 44% in TOWER and 80% and 38% in phase 1b and phase 2, respectively, of Study 265. The Kaplan-Meier (KM) median overall survival was 11.9 months (95% confidence interval [CI], 9.9-17.1) and the KM median duration of relapse-free survival was 8.9 months (95% CI, 3.8-10.7). Ninety-three percent of patients had grade ≥ 3 treatment-emergent adverse events (AEs) compared with 87% in TOWER and 80% and 100% in phase 1b and phase 2, respectively, of Study 265. Five patients (11.4%) had fatal AEs.

Conclusions: The safety and efficacy of blinatumomab in Asian patients were comparable with those reported in previous global studies with no new safety signals.

Keywords: Asia; acute lymphoblastic leukemia (ALL); blinatumomab; post hoc analysis; relapsed/refractory.

Conflict of interest statement

The authors had full access to all data in the study and had final responsibility for the decision to submit for publication. Yukio Kobayashi received research funding from Amgen Astellas BioPharma and Pfizer; received compensation from SymBio for an advisory role; and participated in a speaker's bureau for Amgen Astellas BioPharma and Pfizer. Hironobu Minami received grants from Asahi‐Kasei Pharma, Astellas, Nippon Shinyaku, Taisho Toyama, Teijin Pharma, Yakult, CSL Behring, Nippon Kayaku, and Shionogi; received grants and personal fees from Bayer; received grants and personal fees from Boehringer Ingelheim, Eisai, Kyowa Kirin, Eli Lilly, Merck Serono, Nippon Chemiphar, Sanofi, Takeda, and Sumitomo Dainippon Pharma; received grants and personal fees, personal fees from Bristol Myers Squibb; received personal fees from Celgene, Janssen, Otsuka, Shire Japan, Genomic Health, AbbVie, and Kyowa; received grants and personal fees from Chugai; received grants from Daiichi Sankyo; received grants and personal fees from MSD; received grants and personal fees from Ono Pharmaceutical; received grants, personal fees from Pfizer; received grants and personal fees from Taiho; received personal fees from Novartis; and received personal fees from Nihon Medi‐Physics, outside the submitted work. Yoshinobu Maeda received research funding from Bristol Myers Squibb and Astellas; and received honoraria from Bristol Myers Squibb, Mundipharma, and Kyowa Kirin. Sung‐Soo Yoon received compensation for a consulting or advisory role from Janssen, Takeda, Amgen, Celgene, Novartis, Astellas; received honoraria from Novartis; received research funding from Yuhan Pharmaceutical, Kyowa Kirin, and Roche‐Genentech. Qui Tran, Joan Morris, and Janet Franklin are employees and stockholders of Amgen. Hitoshi Kiyoi received research funding from FUJIFILM, Otsuka, Chugai, Kyowa Kirin, Astellas, Zenoaq Kogyo, Nippon Shinyaku, Eisai, Takeda, Sumitomo Dainippon Pharma, Bristol Myers Squibb, Perseus Proteomics, and Daiichi Sankyo; and received honoraria from Pfizer Japan and Astellas. Hiroatsu Iida received research funding from Chugai. Iekuni Oh, Toshihiro Miyamoto, Won‐Sik Lee, Jun Ho Jang, and Su‐Peng Yeh have nothing to disclose.

© 2021 The Authors. Asia-Pacific Journal of Clinical Oncology published by John Wiley & Sons Australia, Ltd.

Figures

FIGURE 1

Kaplan–Meier estimates of (a) overall survival (b) relapse‐free survival in Asian adult patients. aNote: CR is defined as ≤5% bone marrow blasts with no evidence of disease and full recovery of peripheral blood counts (platelets > 100,000/μl and ANC > 1,000/μl); CRh is defined as ≤5% bone marrow blasts with no evidence of disease and partial recovery of peripheral blood counts (platelets > 50,000/μl and ANC > 500/μl). Abbreviations: ANC, absolute neutrophil count; CI, confidence interval; CR, complete remission with full hematologic recovery; CRh, complete remission with partial hematologic recovery of peripheral blood counts. aPatients who achieved CR/CRh in the first 12 weeks. Vertical bar | indicates a censored patient at the time of allogeneic hematopoietic stem cell transplantation