American Society of Hematology Annual Meeting

Ivosidenib vs Venetoclax: A Comparison of Efficacy, Safety of Regimens for mIDH1 AML

Avatar photoMegan Garlapow, PhD
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Venetoclax and hypomethylating agents appear to be more effective when used together.
Venetoclax and hypomethylating agents appear to be more effective when used together.
This study aimed to compare treatment patterns, efficacy, and safety of 2 frontline regimens in a large cohort of patients with newly diagnosed mutant IDH1 AML.

A comparison of ivosidenib plus hypomethylating agent (IVO+HMA) and venetoclax plus HMA (VEN+HMA) resulted in higher rates of complete response (CR) and CR plus incomplete count or incomplete platelet recovery (CRi/p), achieved CR faster, and had longer event-free survival (EFS) with the ivosidenib combination. These results were presented at the ASH Annual Meeting 2023.

Previous studies are limited in scope and patient numbers, and pooled IDH1 and IDH2 subpopulations. Therefore, this retrospective chart review of 283 patients with newly diagnosed mutant IDH1 acute myeloid leukemia (mIDH1 AML) ineligible for intensive chemotherapy aimed to understand treatment patterns, efficacy, and safety outcomes associated with these regimens specifically in this patient population. 

The study was conducted across community and academic settings from November 2021 to November 2022, and it included 182 patients treated with IVO+HMA and 101 treated with VEN+HMA. Baseline characteristics were comparable between the 2 treatment groups. 

Notably, the IVO+HMA cohort exhibited higher rates of CR and CRi/p compared with the VEN+HMA cohort (63.2% vs 49.5%; P =.025), primarily attributed to the higher CR rate of IVO+HMA (42.9% vs 26.7%; P =.007). 

Median time to the best response was shorter for IVO+HMA than VEN+HMA (3.3 vs 4.1 months; P =.02). Six-month event-free survival (EFS) also favored IVO+HMA (56.0% vs. 39.6%; hazard ratio, 0.773; P =.044). Additionally, bridge to transplant was greater with IVO+HMA (11.5%) compared with VEN+HMA (5.0%), although not statistically significant (P =.066).

Treatment discontinuation rates were equal for both regimens (37%), but febrile neutropenia (grade 3 or higher) rates were higher for VEN+HMA within 30 days of initiation (7.9% vs 1.6% for IVO+HMA; P =.009). 

Patients receiving IVO+HMA showed a significantly lower risk of unscheduled acute care use in the first 12 weeks compared with those receiving VEN+HMA (42.9% vs 70.3%, resulting in a 64% higher relative risk; P <.001). 

Moreover, only 22.8% of patients on VEN+HMA received the full FDA-approved 28 days of venetoclax during the 28-day cycle, with 41.6% receiving 7 or fewer days of venetoclax per cycle, raising concerns about response.

Despite the reduced venetoclax intensity, incidence of febrile neutropenia and need for unscheduled acute care were greater in patients receiving VEN+HMA. 

The analysis also revealed median wait times of 7 days from mIDH1 test to receipt of results for both regimens. However, median time from diagnosis to treatment initiation was shorter for IVO+HMA (14 days vs 20 days for VEN+HMA). 

A higher proportion of patients in the academic setting were treated with VEN+HMA (68.3% vs 55.5% treated with IVO+HMO; P =.035). Clinicians’ response to questions on rationale of treatment choice indicated the use of VEN+HMA was influenced by hospital protocol (30.7% vs. 16.5% for IVO+HMA).

Based on these results, and consistent with the efficacy demonstrated in clinical trial of IVO+azacytidine, the researchers suggest early mutational testing to enable consideration of IVO+azacytidine as frontline treatment for patients with newly diagnosed mIDH1 AML.

Reference

Smith BD, Lachowiez CA, Ambinder AJ, et al. A comparison of acute myeloid leukemia (AML) regimens: hypomethylating agents combined with ivosidenib or venetoclax in newly diagnosed patients with IDH1 mutations: a real-world evidence study. Presented at ASH 2023. December 9-12, 2023. San Diego, CA. Abstract 971.