Blinatumomab for Acute Lymphoblastic Leukemia Relapse after Allogeneic Hematopoietic Stem Cell Transplantation

Anthony S. Stein, Hagop Kantarjian, Nicola Gökbuget, Ralf Bargou, Mark R Litzow, Alessandro Rambaldi, Josep Maria Ribera, Alicia Zhang, Zachary Zimmerman, Gerhard Zugmaier, Max S. Topp

Research output: Contribution to journalArticle

Abstract

Patients with relapsed/refractory (R/R)acute lymphoblastic leukemia (ALL)following allogeneic hematopoietic stem cell transplantation (alloHSCT)have a poor prognosis, and alternative therapies are needed for this patient population. Blinatumomab, a bispecific T cell engager immunotherapy, was evaluated in an open-label, single-arm, phase II study of adults with R/R Philadelphia chromosome-negative B cell precursor ALL and resulted in a rate of complete remission (CR)or CR with partial hematologic recovery of peripheral blood counts (CRh)of 43% within 2 treatment cycles. We conducted an exploratory analysis to determine the efficacy and safety of blinatumomab in 64 patients who had relapsed following alloHSCT before enrollment in the phase II study. Forty-five percent of the patients (29 of 64)achieved a CR/CRh within the first 2 cycles of treatment, 22 of whom had a minimal residual disease (MRD)response (including 19 with a complete MRD response). After 1 year and 3 years of follow-up, the median relapse-free survival was 7.4 months for patients who achieved CR/CRh in the first 2 cycles, and the median overall survival was 8.5 months; overall survival rate (Kaplan-Meier estimate)was 36% at 1 year and 18% at 3 years. Grade 3 and 4 adverse events were reported in 20 patients (31%)and 28 patients (44%), respectively, with grade 3 and 4 neurologic events in 8 and 2 patients, respectively, and grade 3 cytokine release syndrome in 2 patients. Eight patients had fatal adverse events, including 5 due to infections. Seven patients had grade ≤ 3 graft-versus-host disease during the study, none of which resulted in the discontinuation of blinatumomab or hospitalization. Our data suggest that blinatumomab is an effective salvage therapy in this patient population.

Original languageEnglish (US)
JournalBiology of Blood and Marrow Transplantation
DOIs
StatePublished - Jan 1 2019

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Hematopoietic Stem Cell Transplantation
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Recurrence
Residual Neoplasm
blinatumomab
Chromosomes, Human, 4-5
Salvage Therapy
Philadelphia Chromosome
Survival
Kaplan-Meier Estimate
Graft vs Host Disease
Complementary Therapies
Immunotherapy
Nervous System
Population
Hospitalization
B-Lymphocytes
Survival Rate
Cytokines

Keywords

  • Allogeneic hematopoietic stem cell transplantation
  • Blinatumomab
  • Efficacy
  • Philadelphia chromosome-negative B precursor ALL
  • Safety

ASJC Scopus subject areas

  • Hematology
  • Transplantation

Cite this

Blinatumomab for Acute Lymphoblastic Leukemia Relapse after Allogeneic Hematopoietic Stem Cell Transplantation. / Stein, Anthony S.; Kantarjian, Hagop; Gökbuget, Nicola; Bargou, Ralf; Litzow, Mark R; Rambaldi, Alessandro; Ribera, Josep Maria; Zhang, Alicia; Zimmerman, Zachary; Zugmaier, Gerhard; Topp, Max S.

In: Biology of Blood and Marrow Transplantation, 01.01.2019.

Research output: Contribution to journalArticle

Stein, Anthony S. ; Kantarjian, Hagop ; Gökbuget, Nicola ; Bargou, Ralf ; Litzow, Mark R ; Rambaldi, Alessandro ; Ribera, Josep Maria ; Zhang, Alicia ; Zimmerman, Zachary ; Zugmaier, Gerhard ; Topp, Max S. / Blinatumomab for Acute Lymphoblastic Leukemia Relapse after Allogeneic Hematopoietic Stem Cell Transplantation. In: Biology of Blood and Marrow Transplantation. 2019.
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abstract = "Patients with relapsed/refractory (R/R)acute lymphoblastic leukemia (ALL)following allogeneic hematopoietic stem cell transplantation (alloHSCT)have a poor prognosis, and alternative therapies are needed for this patient population. Blinatumomab, a bispecific T cell engager immunotherapy, was evaluated in an open-label, single-arm, phase II study of adults with R/R Philadelphia chromosome-negative B cell precursor ALL and resulted in a rate of complete remission (CR)or CR with partial hematologic recovery of peripheral blood counts (CRh)of 43{\%} within 2 treatment cycles. We conducted an exploratory analysis to determine the efficacy and safety of blinatumomab in 64 patients who had relapsed following alloHSCT before enrollment in the phase II study. Forty-five percent of the patients (29 of 64)achieved a CR/CRh within the first 2 cycles of treatment, 22 of whom had a minimal residual disease (MRD)response (including 19 with a complete MRD response). After 1 year and 3 years of follow-up, the median relapse-free survival was 7.4 months for patients who achieved CR/CRh in the first 2 cycles, and the median overall survival was 8.5 months; overall survival rate (Kaplan-Meier estimate)was 36{\%} at 1 year and 18{\%} at 3 years. Grade 3 and 4 adverse events were reported in 20 patients (31{\%})and 28 patients (44{\%}), respectively, with grade 3 and 4 neurologic events in 8 and 2 patients, respectively, and grade 3 cytokine release syndrome in 2 patients. Eight patients had fatal adverse events, including 5 due to infections. Seven patients had grade ≤ 3 graft-versus-host disease during the study, none of which resulted in the discontinuation of blinatumomab or hospitalization. Our data suggest that blinatumomab is an effective salvage therapy in this patient population.",
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AU - Litzow, Mark R

AU - Rambaldi, Alessandro

AU - Ribera, Josep Maria

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