Transformative Outcomes with Short-Term Blinatumomab and Cord Blood Transplantation in Relapsed/Refractory B-Cell ALL

[Background] Blinatumomab is a bispecific T-cell engager (BiTE) antibody with specificity for both CD19, expressed on B cells, and CD3, expressed on T cells. While blinatumomab is known for its efficacy in relapsed or refractory B-cell acute lymphoblastic leukemia (R/R B-ALL), reports on its use before transplantation are limited, and there are no reports on its use before cord blood transplantation (CBT).

[Objective and Methods] To assess the efficacy, safety, clinical features, and outcomes of blinatumomab before CBT in patients with R/R B-ALL, we retrospectively analyzed patients who received CBT after using blinatumomab for R/R B-ALL at our institution from August 2019 to July 2023.

[Result] During the study period, 42 patients received CBT after using blinatumomab for R/R B-ALL in our institute. The median follow-up duration for survivors was 438 days (range: 69-1466). The median age of the patients was 53 years (range: 16-71), with 27 males and 15 females. Among the 42 cases, 12 had Philadelphia chromosome-positive ALL; all 12 cases received blinatumomab in combination with a tyrosine kinase inhibitor. Twenty-four patients received blinatumomab after relapse following chemotherapy, 9 patients had induction failure, 6 patients had minimal residual disease after chemotherapy, and 3 patients received it for other reasons. The median number of blinatumomab courses in this group was 2 (range: 1-4). Treatment discontinuation occurred in 14 cases for the following reasons: liver dysfunction in 4 cases, hypotension in 3 cases, neurological impairment in 3 cases, disease progression in 2 cases, and other reasons in 2 cases. In 8 of the 14 cases where treatment was discontinued, blinatumomab was resumed after steroid therapy. After using blinatumomab, complete remission (CR) was achieved in 35 of the 42 cases (83%). The final disease status at the time of transplantation was CR in 36 cases and non-CR in 6 cases. All 42 cases used CBT as the donor source. Twenty-eight patients received myeloablative pretransplant conditioning, and 14 received reduced-intensity conditioning. The 2-year overall survival (OS) for the 42 cases was 77.9%, progression-free survival (PFS) was 68.6%, relapse rate was 14.6%, and non-relapse mortality cumulative incidence was 25.3%. For patients who received CBT in non-CR, the probability of OS and PFS were lower compared to patients in CR (2-year OS, CR vs. non-CR, 82.6% vs. 50.0%, p = 0.025; 2-year PFS, CR vs. non-CR, 73.1% vs. 41.7%, p = 0.006).

[Discussion] Short-term use of blinatumomab before CBT for R/R B-ALL was safe and effective. Our data indicate that the combination of short-term blinatumomab and CBT could become a formidable treatment option for overcoming R/R B-ALL.

Kaji:Meiji Seika Pharma Co.: Honoraria; AstraZeneca: Honoraria; Bristol Myers Squibb K.K.: Honoraria; Genmab: Honoraria; Asahi Kasei Pharma Co.: Honoraria; Eisai Co.: Honoraria; Chugai Pharmaceutical Co.: Honoraria; Janssen Pharmaceutical KK.: Honoraria; AbbVie GK.: Honoraria; Ono Pharmaceutical Co.: Honoraria; Pfizer Japan Inc.: Honoraria; Sanofi K.K.: Honoraria; SymBio Pharmaceuticals: Honoraria; Takeda Pharmaceutical Co.: Honoraria. Takagi:Otsuka Pharmaceutical Co.: Honoraria; Novartis Pharma Co.: Honoraria; Nippon Shinyaku Co.: Honoraria; MSD KK (Merck & Co. Inc.): Honoraria; Kyowa Kirin Co.: Honoraria; Janssen Pharmaceutical KK.: Honoraria; GlaxoSmithKline KK.: Honoraria; Daiichi Sankyo Co.: Honoraria; Chugai Pharmaceutical Co.: Honoraria; Astellas Pharma Inc.: Honoraria; Asahi Kasei Pharma Co.: Honoraria; Amgen KK.: Honoraria; AbbVie GK.: Honoraria; The Japanese Society of Hematology: Research Funding; Okinaka Memorial Institute for Medical Research: Research Funding; Pfizer Japan Inc.: Honoraria; Sumitomo Pharma Co.: Honoraria; Takeda Pharmaceutical Co.: Honoraria. Yamamoto:Sumitomo Pharma CO.,Ltd.: Honoraria; Astellas Pharma Inc.: Honoraria; MSD KK (Merck & Co.) Inc.: Honoraria; JCR Pharmaceuticals Co.,Ltd.: Honoraria; Janssen Pharmaceutical KK: Honoraria; Novartis Pharma Co.: Honoraria; Otsuka Pharmaceutical Co.: Honoraria; CSL Behring K.K: Honoraria; AstraZeneca: Honoraria; Chugai Pharmaceutical Co.: Honoraria; Takeda Pharmaceutical Co.: Honoraria; Asahi Kasei Pharma Co.: Honoraria. Yamamoto:Janssen Pharmaceutical KK.: Honoraria; Meiji Seika Pharma Co.: Honoraria; Mundi Pharma Co.: Honoraria; Nihonkayaku Co.: Honoraria; Novartis Pharma Co.: Honoraria; Chugai Pharmaceutical Co.: Honoraria; Bristol Myers Squibb K.K.: Honoraria; AstraZeneca: Honoraria; Daiichi Sankyo Co.: Honoraria; Eisai Co.: Honoraria; Genmab: Honoraria; Ono Pharmaceutical Co.: Honoraria; Pfizer Japan Inc.: Honoraria; Sanofi K.K.: Honoraria; Takeda Pharmaceutical Co.: Honoraria. Uchida:Chugai Pharmaceutical Co.: Honoraria; SymBio Pharmaceuticals: Honoraria; Takeda Pharmaceutical Co.: Honoraria; Kyowa Kirin Co.: Honoraria; AbbVie GK: Honoraria; Otsuka Pharmaceutical Co.: Honoraria; Daiichi Sankyo Co.: Honoraria; Astellas Pharma Inc.: Consultancy; Nippon Shinyaku Co.: Honoraria; Novartis Pharma Co.: Honoraria; AstraZeneca: Honoraria; Astellas Pharma Inc.: Honoraria; Asahi Kasei Pharma Co.: Honoraria; MSD (Merck & Co. Inc.): Honoraria; CSL Behring: Honoraria; JCR Pharmaceuticals Co.: Research Funding; Nippon Boehringer Ingelheim Co.: Research Funding; Sumitomo Pharma Co.: Research Funding; Fuji Pharma Co.: Research Funding; Chugai Pharmaceutical Co.: Research Funding; Takeda Pharmaceutical Co.: Consultancy.