Estimating Long-Term Survival of Adults with Philadelphia Chromosome-Negative Relapsed/Refractory B-Precursor Acute Lymphoblastic Leukemia Treated with Blinatumomab Using Historical Data

Abstract

Introduction: Blinatumomab is a bispecific T cell-engaging antibody construct indicated for adult patients with relapsed/refractory (R/R) Ph(-) B-precursor acute lymphoblastic leukemia (ALL), an aggressive disease with poor prognosis. A phase 2 single-arm clinical study showed that 43% of patients achieved CR/CRh within two cycles and approximately 20% of patients receiving blinatumomab were still alive after 2 years.

Methods: The objective of the current analysis was to estimate long-term survival of patients receiving blinatumomab beyond the observed time period in the clinical study using a large historical observational dataset. Conditional survival probabilities of blinatumomab-treated patients beyond month 60 were assumed to be the same as the US general population.

Results: At month 60, the estimated proportion of blinatumomab-treated patients alive was more than double that of historical patients (12.6% vs 5.4%). The mean overall survival was 76.1 months for blinatumomab patients and 39.8 months for historical patients. Sensitivity analyses including additional follow-up data from the clinical study showed consistent results.

Conclusions: These findings suggest that blinatumomab provides substantial overall survival benefit to patients with (R/R) Ph(-) B-precursor ALL compared with salvage chemotherapy.

Funding: Amgen.

Trial registration: ClinicalTrials.gov identifier NCT01466179 and NCT02003612.

Keywords: Acute lymphoblastic leukemia; Blinatumomab; Hematology; Long-term survival; Oncology.

Fig. 1

5-year survival curves for patients receiving blinatumomab and historical dataset

Fig. 2

Validation based on 36 months of observed data from the blinatumomab clinical trial