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TOPLINE:

Ivosidenib combined with azacitidine extended median overall survival to 29.3 months compared with 7.9 months for placebo plus azacitidine in newly diagnosed isocitrate dehydrogenase 1 (IDH1)-mutated acute myeloid leukemia (AML). The combination therapy also improved hematologic recovery and increased transfusion independence rate to 53.8% vs 17.1% with placebo.

METHODOLOGY:

• A total of 148 patients with newly diagnosed IDH1-mutated AML who were unfit for intensive chemotherapy were randomized to receive either ivosidenib-azacitidine (n = 73) or placebo-azacitidine (n = 75).
• Treatment consisted of 500 mg ivosidenib or placebo administered orally once daily, combined with subcutaneous or intravenous 75 mg/m² azacitidine for 7 days in 28-day cycles, with randomization stratified by geographic region and disease status.
• Analysis included a median follow-up period of 28.6 months, with overall survival as the key outcome measure, along with hematologic recovery, transfusion independence, and molecular measurable residual disease response.

TAKEAWAY:

• Median overall survival was significantly longer with ivosidenib-azacitidine at 29.3 months (95% CI, 13.2-not reached) compared to 7.9 months (95% CI, 4.1-11.3) with placebo-azacitidine (hazard ratio [HR], 0.42; 95% CI, 0.27-0.65; P < .0001).
• Among patients who were transfusion dependent at baseline, conversion to transfusion independence was achieved in 53.8% (21/39) of ivosidenib-azacitidine patients vs 17.1% (7/41) of placebo-azacitidine patients (P = .0004).
• Of 33 ivosidenib-treated patients evaluable for molecular measurable residual disease, 10 (30.3%) achieved MRD negativity by day 1 of cycle 14, all of whom had complete remission.
• The safety profile remained consistent with previous reports, with lower rates of febrile neutropenia and infections in the ivosidenib-azacitidine arm, though neutropenia and bleeding events were more common than with placebo.

IN PRACTICE:

“These long-term efficacy and safety results confirm the benefit of ivosidenib-azacitidine in this challenging-to-treat population and support its use as a standard of care with the longest reported survival benefit for intensive chemotherapy-ineligible patients with IDH1-mutated AML,” the authors of the study wrote.

SOURCE:

The study was led by Pau Montesinos, Hospital Universitari i Politécnic La Fe in Valencia, Spain, and Hartmut Döhner, Ulm University Hospital in Ulm, Germany. It was published online in Blood Advances.

LIMITATIONS:

According to the authors, molecular response analysis was limited by the small number of measurable residual disease-evaluable patients and samples, as well as the discontinuation of sample collection after study unblinding in March 2021. The limited number of variants that could be tracked with sufficient sensitivity in panel-based next-generation sequencing measurable residual disease assessment also constrained the molecular analyses.

DISCLOSURES:

Montesinos disclosed having relationships with AbbVie, Bristol Myers Squibb, Daiichi Sankyo, Jazz Pharmaceuticals, Novartis, Pfizer, Sanofi, Servier, and Teva Pharmaceuticals. Additional disclosures are noted in the original article.

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