Blinatumomab vs historic standard‐of‐care treatment for minimal residual disease in adults with B‐cell precursor acute lymphoblastic leukaemia

Abstract

Objectives Survival outcomes from a single‐arm phase 2 blinatumomab study in patients with minimal residual disease (MRD)‐positive B‐cell precursor (BCP)‐acute lymphoblastic leukaemia (ALL) were compared with those receiving standard of care (SOC) in a historic data set. Methods The primary analysis comprised adult Philadelphia chromosome (Ph)‐negative patients in first complete haematologic remission (MRD ≥ 10−3). Relapse‐free survival (RFS) and overall survival (OS) were compared between blinatumomab‐ and SOC‐treatment groups. Baseline differences between groups were adjusted by propensity scores. Results The primary analysis included 73 and 182 patients from the blinatumomab and historic data sets, respectively. When weighted by age to the blinatumomab‐treatment group, median RFS was 7.8 months and median OS was 25.9 months in the SOC‐treated group. In the blinatumomab study, median RFS was 35.2 months; median OS was not evaluable. Propensity score weighting achieved balance with seven baseline prognostic factors. With adjustment for haematopoietic stem cell transplantation (HSCT) status, a 50% reduction in risk of relapse or death was observed with blinatumomab vs SOC. Median RFS, unadjusted for HSCT status, was 35.2 months with blinatumomab and 8.3 months with SOC. Conclusions These analyses suggest that blinatumomab improves RFS, and possibly OS, in adults with MRD‐positive Ph‐negative BCP‐ALL vs SOC.

PD-1 Inhibition Enhances Blinatumomab Response in a UCB/PDX Model of Relapsed Pediatric B-Cell Acute Lymphoblastic Leukemia

“…The method relies on a readily available source of stem cells and avoids GVHD and labor-intensive steps of other models. Our model of early treatment with blinatumomab after engraftment mimics several completed and ongoing clinical trials in which blinatumomab has been used against residual post chemotherapy MRD (7,10,20). One question that remains unanswered is if blinatumomab could be used concurrently or consecutively with conventional chemotherapy, and how the lymphotoxic effects of chemotherapy impact efficacy of blinatumomab (21).…”

“…Recently, new effective therapies for patients in relapse have further improved survival, including the CD19directed Bi-specific T cell Engager (BiTE), blinatumomab. As a treatment for therapy resistant disease, blinatumomab has been shown to lead to longer relapse free survival compared to historical data using standard chemotherapy approaches in adult patients (7). A group of 20 such patients who received blinatumomab achieved a long-term relapse free survival of 60-65% at 3 years, regardless of HSCT (8).…”

Bispecific T cell engagers: an emerging therapy for management of hematologic malignancies

“…Thus, early administration of blinatumomab is beneficial to B-ALL patients with MRD (NCT01207388) [ 48 ]. Compared with standard chemotherapy, blinatumomab was associated with a higher rate of CR and longer overall survival [ 49 ]. Moreover, administration of blinatumomab before allogeneic stem cell transplantation improved the rate of CR, which indicated that blinatumomab could be a bridge to allogeneic stem cell transplantation (NCT02013167) [ 50 ].…”

Real‐world evidence to support regulatory decision making: New or expanded medical product indications

“…Historical control data also contributed to an expanded indication for this drug for the treatment of patients with minimal residual disease. 42 A more traditional example is the approval of intracerebroventricular cerliponase alfa for the treatment of infantile batten disease, where data from a dose escalation trial was compared against historical controls. 43 Despite mounting success of external controls to support drug approvals, there have also been some notable failures.…”