TOPLINE

Adding blinatumomab to consolidation and maintenance chemotherapy was associated with a reduced risk for relapse and improved disease-free and overall survival in adults with high-risk Philadelphia chromosome-negative (Ph-) B-cell acute lymphoblastic leukemia (B-ALL) compared with standard chemotherapy alone in a phase 2 trial.

METHODOLOGY

• Intensified chemotherapy has improved outcomes in adults with Ph- B-ALL, but many patients relapse. In the current analysis, researchers assessed whether integrating blinatumomab, a CD19-directed bispecific antibody, into consolidation and maintenance therapies in patients with high-risk B-ALL.
• The multicenter, open-label phase 2 trial (GRAALL-2014/B-QUEST), designed as a nested trial within the broader GRAALL-2014 protocol, included adults aged 18-59 years with newly diagnosed Ph- B-ALL, enrolled between December 2015 and December 2020.
• Overall, 94 patients with high-risk disease received up to five 28-day cycles of blinatumomab added to standard consolidation and maintenance chemotherapy. Researchers compared outcomes with an internal historical control cohort of 90 patients who received the same chemotherapy backbone without blinatumomab. High-risk disease was defined as the presence of KMT2A rearrangement, IKZF1 deletion, or end-of-induction minimal residual disease (MRD) ≥ 10^-4.
• The primary outcome was the 3-year disease-free survival rate. Other outcomes included the cumulative incidence of relapse and overall survival.
• Patients with very high-risk disease (defined as having MRD ≥ 10^-3 after induction or MRD ≥ 10^-4 after the first consolidation) were eligible for allogeneic hematopoietic stem cell transplantation (alloHSCT); transplant rates among patients with very high-risk disease were higher in the QUEST study than in the control group (88% vs 65%). 

TAKEAWAY

• The 3-year rate of disease-free survival was 70% in the blinatumomab group vs 48% in the control group. At 5 years, the cumulative incidence of relapse was significantly lower in the blinatumomab group — 23% vs 49% — and the rates of disease-free and overall survival were significantly higher — 68% vs 42%, and 79% vs 60%, respectively.
• After the second consolidation, undetectable MRD was achieved more often with blinatumomab than chemotherapy alone — 72% vs 55% (P = .041). Among patients with preconsolidation MRD of at least 10^-4, conversion to undetectable MRD was also higher in the blinatumomab group — 51% vs 17% (P = .008).
• In multivariable analyses adjusted for baseline covariates, exposure to blinatumomab remained independently associated with significantly improved disease-free survival (hazard ratio [HR], 0.47), a reduced cumulative incidence of relapse (subdistribution HR, 0.38), and improved overall survival (HR, 0.50).
• Among patients with very high-risk disease who were eligible for alloHSCT, blinatumomab was associated with improved disease-free survival (HR, 0.54) and lower relapse incidence (subdistribution HR, 0.41). However, among patients who ultimately underwent transplantation, prior blinatumomab exposure was not associated with additional disease-free survival benefit (HR, 0.76; 95% CI, 0.39-1.50).

IN PRACTICE

“Our study shows a valuable benefit of blinatumomab in a [high-risk] population of patients. Although the benefit of blinatumomab is observed in almost all subgroups, this study did not detect a benefit of prior blinatumomab treatment in the specific subgroup of patients who were bridged to alloHSCT because of a poor MRD response to chemotherapy,” the authors of the study wrote.

An accompanying editorial described the findings as further evidence supporting earlier incorporation of blinatumomab into frontline therapy while noting that the optimal role of allogeneic transplantation after blinatumomab remains unresolved.

SOURCE

The study, led by Nicolas Boissel, MD, Département d’Hématologie, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris in Paris, France, was published online in Blood, alongside an accompanying editorial.

LIMITATIONS

The post hoc analysis was a nonrandomized comparison within the same parent protocol, which limited the strength of causal inferences. The comparison relied on an internal nonrandomized historical control cohort rather than randomized assignment. Interpretation of findings regarding alloHSCT was limited by the nonrandomized design, differences in transplant rates between cohorts, and the small number of nontransplanted patients who were very high-risk. Immortal time bias may have affected results because patients had to remain in remission to receive blinatumomab.

DISCLOSURES

The study received support from the Paris Ile-de-France Regional Clinical Research Office and grants from the Programme Hospitalier de Recherche Clinique in France and the Swiss State Secretariat for Education, Research and Innovation. Amgen provided support for the study and supplied blinatumomab. Boissel disclosed receiving honoraria from Amgen, Novartis, Pfizer, Servier, and Gilead. Full disclosures are noted in the original article and editorial.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.