GMALL-BLIVEN trial: Venetoclax + blinatumomab in R/R or MRD+ Ph− B-ALL

Results from the phase I, multicenter GMALL-BLIVEN trial (NCT05182385), evaluating the safety and feasibility of venetoclax (Ven) + blinatumomab (Blina) in adults with CD19⁺, Philadelphia chromosome-negative (Ph−) relapsed/refractory (R/R; n = 4) or measurable residual disease (MRD)-positive (n = 5) B-cell precursor acute lymphoblastic leukemia (B-ALL), were published in Annals of Hematology by Fransecky et al. The study followed a 3+3 dose-escalation, with Ven administered from Day −7 to Day 42 at 400 mg (dose level [DL]–1), 600 mg (DL–2), or 800 mg (DL–3), with Blina given per label. The primary endpoint was determination of the maximum tolerated dose (MTD). A key secondary endpoint was achievement of molecular complete response (MOL‑CR), assessed by centralized immunoglobulin/T-cell receptor (IG/TR) MRD testing (sensitivity ≥ 10⁻⁴).

Key data: Of the nine patients in the study, no dose-limiting toxicities (DLTs) were observed and the MTD was not reached; the recommended phase II dose (RP2D) was Ven 800 mg daily + standard-dose Blina. Grade ≥3 treatment-emergent toxicities included neutropenia (n = 1), febrile neutropenia (n = 1), immune effector cell-associated neurotoxicity syndrome (ICANS; n = 2), and cytokine release syndrome (CRS; n = 2); no 30- or 60-day deaths occurred. No correlation was observed between DL and response; among patients with R/R B‑ALL, treatment resulted in partial response (PR; n = 1), complete response (CR; n = 1), or progressive disease (PD; n = 2), while 4/5 patients with MRD⁺ disease achieved MOL‑CR. Four deaths were reported during follow-up, all due to PD; median overall survival (OS) was 15.0 months, 6.6 months, and 16.9 months in the overall, R/R, and MRD⁺ cohorts, respectively. 

Key learning: The phase I trial showed Ven + Blina was safe to combine in adults with Ph– R/R or MRD⁺ B-ALL, with no DLTs observed; however, evaluation of therapeutic efficacy is limited by the low number of patients. The ongoing phase II evaluation of this therapy will assess its efficacy in this high-risk patient population.