Blinatumomab treatment of older adults with relapsed/refractory B-precursor acute lymphoblastic leukemia: Results from 2 phase 2 studies

Cancer. 2016 Jul 15;122(14):2178-85. doi: 10.1002/cncr.30031. Epub 2016 May 3.

Abstract

Background: Older adults with relapsed/refractory B-precursor acute lymphoblastic leukemia (r/r ALL) are reported to have a poor prognosis and few therapeutic options. In the current study, the authors evaluated treatment with single-agent blinatumomab in adults aged ≥65 years with r/r ALL.

Methods: A total of 261 adults with r/r ALL who were examined across two phase 2 studies received blinatumomab in cycles of 4-week continuous infusion and 2-week treatment-free intervals. The primary endpoint in each study was complete remission (CR) or CR with partial hematologic recovery (CRh) during the first 2 cycles. Data were pooled and analyzed according to patient age at screening (aged ≥65 years vs aged <65 years).

Results: Of 36 older adults, 56% (95% confidence interval [95% CI], 38%-72%) achieved CR/CRh during the first 2 cycles compared with 46% (225 patients) (95% CI, 40%-53%) of younger adults. Complete minimal residual disease responses were 60% in older and 70% in younger responders. Three older responders (15%) and 61 younger responders (59%) proceeded to allogeneic hematopoietic stem cell transplantation. Kaplan-Meier curves overlapped for relapse-free and overall survival for both age groups. Older adults were found to have a similar incidence of grade ≥3 adverse events (AEs) as younger adults (86% vs 80%) but more grade ≥3 neurologic events (28% vs 13%). Cytokine release syndrome occurred in 7 older (19%) (1 case of grade 3) and 23 younger (10%) (4 cases of grade ≥3) adults. There were no treatment-related fatal AEs reported.

Conclusions: Older adults with r/r ALL who were treated with single-agent blinatumomab were found to have similar hematologic response rates and incidence of grade ≥3 AEs compared with younger adults but had more neurologic events, which were reversible and primarily resolved with treatment interruption. Cancer 2016;122:2178-85. © 2016 American Cancer Society.

Keywords: acute lymphoblastic leukemia; bispecific antibodies; blinatumomab; elderly; relapsed/refractory.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Bispecific / therapeutic use*
  • Antineoplastic Agents / therapeutic use*
  • Clinical Trials, Phase II as Topic
  • Drug Resistance, Neoplasm
  • Female
  • Hematopoietic Stem Cell Transplantation
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Molecular Targeted Therapy
  • Multicenter Studies as Topic
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / mortality
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / pathology*
  • Recurrence
  • Retreatment
  • Transplantation, Homologous
  • Treatment Outcome
  • Young Adult

Substances

  • Antibodies, Bispecific
  • Antineoplastic Agents
  • blinatumomab