Safety and activity of blinatumomab for adult patients with relapsed or refractory B-precursor acute lymphoblastic leukaemia: a multicentre, single-arm, phase 2 study
Phase 2 or 3 results paper on Blinatumomab in Acute lymphoblastic leukaemia, in The Lancet Oncology (2015), one of the most cited Europe PMC records with Blinatumomab in its title.
Overview
Background: Adults with relapsed or refractory B-precursor acute lymphoblastic leukaemia have an unfavourable prognosis. Blinatumomab is a bispecific T-cell engager antibody construct targeting CD19, an antigen consistently expressed on B-lineage acute lymphoblastic leukaemia cells. We aimed to confirm the activity and safety profile of blinatumomab for acute lymphoblastic leukaemia.
Methods: In a multicentre, single-arm, open-label phase 2 study, we enrolled adult patients with Philadelphia-chromosome-negative, primary refractory or relapsed (first relapse within 12 months of first remission, relapse within 12 months after allogeneic haemopoietic stem-cell transplantation [HSCT], or no response to or relapse after first salvage therapy or beyond) leukaemia. Patients received blinatumomab (9 μg/day for the first 7 days and 28 μg/day thereafter) by continuous intravenous infusion over 4 weeks every 6 weeks (up to five cycles), per protocol. The primary endpoint was complete remission (CR) or CR with partial haematological recovery of peripheral blood counts (CRh) within the first two cycles. Analysis was by intention to treat. This trial is registered at ClinicalTrials.gov, number NCT01466179.
Findings: Between Jan 13, 2012, and Oct 10, 2013, 189 patients were enrolled and treated with blinatumomab. After two cycles, 81 (43%, 95% CI 36-50) patients had achieved a CR or CRh: 63 (33%) patients had a CR and 18 (10%) patients had a CRh. 32 (40%) of patients who achieved CR/CRh underwent subsequent allogeneic HSCT. The most frequent grade 3 or worse adverse events were febrile neutropenia (48 patients, 25%), neutropenia (30 patients, 16%), and anaemia (27 patients, 14%). Three (2%) patients had grade 3 cytokine release syndrome. Neurologic events of worst grade 3 or 4 occurred in 20 (11%) and four (2%) patients, respectively. Three deaths (due to sepsis, Escherichia coli sepsis, and Candida infection) were thought to be treatment-related by the investigators.
Interpretation: Single-agent blinatumomab showed antileukaemia activity in adult patients with relapsed or refractory B-precursor acute lymphoblastic leukaemia characterised by negative prognostic factors. Further assessment of blinatumomab treatment earlier in the course of the disease and in combination with other treatment approaches is warranted.
Funding: Amgen.
Indexed on Europe PMC as PubMed record 25524800 (DOI 10.1016/s1470-2045(14)71170-2). Its title names Blinatumomab and its text names Acute lymphoblastic leukaemia; PubMed types it as a clinical trial report (Clinical Trial, Phase II, Research Support, Non-U.S. Gov't, Multicenter Study). It was matched automatically to the idea "Menin inhibitors for infant KMT2A-rearranged ALL" and no figure has been checked by an editor.
One of the most cited trial reports Europe PMC returns for Blinatumomab in Acute lymphoblastic leukaemia, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.
- Matched by Blinatumomab in the title and Acute lymphoblastic leukaemia in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.
- Chosen as a phase 2 or 3 report by the record's publication type or its own wording, not by reading the paper.