Long-term survival of patients with relapsed/refractory acute lymphoblastic leukemia treated with blinatumomab

Abstract

Background: Blinatumomab is a CD19 BiTE (bispecific T-cell engager) immuno-oncology therapy that mediates the lysis of cells expressing CD19.

Methods: A pooled analysis of long-term follow-up data from 2 phase 2 studies that evaluated blinatumomab in heavily pretreated adults with Philadelphia chromosome-negative, relapsed/refractory B-cell precursor acute lymphoblastic leukemia was conducted.

Results: A total of 259 patients were included in the analysis. The median overall survival (OS) among all patients, regardless of response, was 7.5 months (95% confidence interval [CI], 5.5-8.5 months); the median follow-up time for OS was 36.0 months (range, 0.3-60.8 months). The median relapse-free survival (RFS) among patients who achieved a complete remission (CR) or complete remission with partial hematologic recovery (CRh) in the first 2 cycles (n = 123) was 7.7 months (95% CI, 6.2-10.0 months); the median follow-up time for RFS was 35.0 months (range, 9.5-59.5 months). OS and RFS plateaued with 3-year rates of 17.7% and 23.4%, respectively. The cumulative incidence function of the time to relapse, with death not due to relapse considered a competing risk, for patients who achieved a CR/CRh within 2 cycles of treatment also plateaued with a 3-year relapse rate of 59.3%. For patients who achieved a CR/CRh with blinatumomab followed by allogeneic hematopoietic stem cell transplantation while in continuous CR, the median OS was 18.1 months (95% CI, 10.3-30.0 months) with a 3-year survival rate of 37.2%.

Conclusions: These data suggest that long-term survival is possible after blinatumomab therapy.

Lay summary: Immuno-oncology therapies such as blinatumomab activate the patient's own immune system to kill cancer cells. This study combined follow-up data from 2 blinatumomab-related clinical trials to evaluate long-term survival in patients with relapsed and/or refractory B-cell precursor acute lymphoblastic leukemia at high risk for unfavorable outcomes. Among patients who achieved a deep response with blinatumomab, one-third lived 3 years or longer. These findings suggest that long-term survival is possible after treatment with blinatumomab.

Keywords: acute lymphoblastic leukemia (ALL); bispecific T-cell engager (BiTE); blinatumomab; overall survival.

Figure 1

OS, RFS, and cumulative incidence function of the time to relapse: (A) OS KM curve and estimates at specific time points for the overall patient population, (B) RFS KM curve and estimates at specific time points for the overall patient population, (C) OS KM curve for patients who underwent HSCT after achieving a CR/CRh, and (D) cumulative incidence function of the time to relapse and estimates at specific time points for the overall patient population. OS was measured from the time of the first blinatumomab dose to death from any cause, and RFS was measured from the time of first CR or CRh within the first 2 cycles to hematologic or extramedullary relapse or death resulting from any cause. Patients who were alive were censored on the last documented visit date or the date of the last phone contact. The cumulative incidence function of the time to relapse with death from nonrelapse as a competing risk was determined for patients who achieved a CR/CRh within 2 cycles of treatment. Error bars represent 95% confidence intervals. CR indicates complete remission; CRh, complete remission with partial hematologic recovery; HSCT, allogeneic hematopoietic stem cell transplantation; KM, Kaplan‐Meier; OS, overall survival; RFS, relapse‐free survival.