Blinatumomab Maintenance After Allogeneic Hematopoietic Cell Transplantation for B-Lineage Acute Lymphoblastic Leukemia

Authors

Mahmoud R Gaballa
Pinaki Banerjee
Denái R Milton
Xianli Jiang
Christina Ganesh
Sajad Khazal
Vandana Nandivada
Sanjida Islam
Mecit Kaplan
May Daher
Rafet Basar
Amin Alousi
Rohtesh Mehta
Gheath Alatrash
Issa Khouri
Betul Oran
David Marin
Uday Popat
Amanda Olson
Priti Tewari
Nitin Jain
Elias Jabbour
Farhad Ravandi
Hagop Kantarjian
Ken Chen
Richard Champlin
Elizabeth Shpall
Katayoun Rezvani
Partow Kebriaei

Publication Date

3-24-2022

Journal

Blood

DOI

10.1182/blood.2021013290

PMID

34914826

PMCID

PMC8952188

PubMedCentral® Posted Date

3-24-2022

PubMedCentral® Full Text Version

Post-print

Abstract

Patients with B-lineage acute lymphoblastic leukemia (ALL) are at high-risk for relapse after allogeneic hematopoietic cell transplantation (HCT). We conducted a single-center phase 2 study evaluating the feasibility of 4 cycles of blinatumomab administered every 3 months during the first year after HCT in an effort to mitigate relapse in high-risk ALL patients. Twenty-one of 23 enrolled patients received at least 1 cycle of blinatumomab and were included in the analysis. The median time from HCT to the first cycle of blinatumomab was 78 days (range, 44 to 105). Twelve patients (57%) completed all 4 treatment cycles. Neutropenia was the only grade 4 adverse event (19%). Rates of cytokine release (5% G1) and neurotoxicity (5% G2) were minimal. The cumulative incidence of acute graft-versus-host disease (GVHD) grades 2 to 4 and 3 to 4 were 33% and 5%, respectively; 2 cases of mild (10%) and 1 case of moderate (5%) chronic GVHD were noted. With a median follow-up of 14.3 months, the 1-year overall survival (OS), progression-free survival (PFS), and nonrelapse mortality (NRM) rates were 85%, 71%, and 0%, respectively. In a matched analysis with a contemporary cohort of 57 patients, we found no significant difference between groups regarding blinatumomab's efficacy. Correlative studies of baseline and posttreatment samples identified patients with specific T-cell profiles as "responders" or "nonresponders" to therapy. Responders had higher proportions of effector memory CD8 T-cell subsets. Nonresponders were T-cell deficient and expressed more inhibitory checkpoint molecules, including T-cell immunoglobulin and mucin domain 3 (TIM3). We found that blinatumomab postallogeneic HCT is feasible, and its benefit is dependent on the immune milieu at time of treatment. This paper is posted on ClinicalTrials.gov, study ID: NCT02807883.

Keywords

Acute Disease, Antibodies, Bispecific, Graft vs Host Disease, Hematopoietic Stem Cell Transplantation, Humans, Lymphoma, B-Cell, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Recurrence

Published Open-Access

yes

Recommended Citation

Gaballa, Mahmoud R; Banerjee, Pinaki; Milton, Denái R; et al., "Blinatumomab Maintenance After Allogeneic Hematopoietic Cell Transplantation for B-Lineage Acute Lymphoblastic Leukemia" (2022). Faculty, Staff and Student Publications. 2805.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/2805