Comparison of the efficacy and safety of Ivosidenib and Venetoclax in the treatment of intermediate-stage acute myeloid leukemia

A comparison of Ivosidenib plus a hypomethylating agent (IVO+HMA) and venetoclax plus an HMA (VEN+HMA) showed that the ivosidenib combination resulted in higher complete response rates (CR) and CR plus incomplete count or incomplete platelet recovery rate (CRi/p), faster CR, and longer event-free survival (EFS). Previous studies were limited in scope and number of patients and combined IDH1 and IDH2 subpopulations. Therefore, this retrospective chart review of 283 patients with newly diagnosed mutant IDH1 acute myeloid leukemia (mIDH1 AML) aimed to understand the treatment patterns, efficacy, and safety of these regimens in this patient population.

The study was conducted in community and academic institutions from November 2021 to November 2022, including 182 patients treated with IVO+HMA and 101 patients treated with VEN+HMA. Baseline characteristics were comparable between the two treatment groups. Notably, the IVO+HMA cohort showed higher CR and CRi/p rates compared with the VEN+HMA cohort (63.2% vs. 49.5%; p=0.025), which was mainly attributed to the higher CR rate of IVO+HMA (42.9% vs. 26.7%; p=0.007).

The median time to best response was shorter with IVO+HMA than with VEN+HMA (3.3 months vs. 4.1 months; p=0.02). Six-month event-free survival (EFS) also favored IVO+HMA (56.0% vs. 39.6%; hazard ratio, 0.773; p=0.044). Furthermore, IVO+HMA resulted in a larger graft bridge (11.5%) compared with VEN+HMA (5.0%), although this was not statistically significant (P0.066). Treatment discontinuation rates were equal between the two regimens (37%), but the rate of febrile neutropenia (grade 3 or higher) within 30 days of starting treatment was higher in the VEN+HMA group (7.9% vs. 1.6% in the IVO+HMA group; p=0.009).

Patients who received IVO+HMA had a significantly lower risk of using unscheduled acute care within the first 12 weeks compared with patients who received VEN+HMA (42.9% vs. 70.3%, resulting in a 64% relative risk increase; P<0.001). Additionally, only 22.8% of VEN+HMA patients received a full 28 days of FDA-approved venetoclax therapy in a 28-day cycle, with 41.6% receiving 7 days or less of venetoclax per cycle, raising concerns about response. Despite the reduced intensity of venetoclax, the incidence of febrile neutropenia and need for unplanned acute care was higher in patients receiving VEN + HMA.

The analysis also showed that the average waiting time from H1 interim testing to receipt of results was seven days for both regimens. However, the median time from diagnosis to initiation of treatment was shorter with IVO+HMA (14 days vs. 20 days with VEN+HMA). A higher proportion of academic patients received VEN+HMA (68.3% vs. 55.5% received IVO+HMO; p=0.035). Clinician responses to questions on the rationale for treatment selection indicated that use of IVO+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 trials of IVO+HMA, the researchers recommend early mutation testing to consider ivonib plus a hypomethylating agent (IVO+HMA) as a first-line treatment for patients with newly diagnosed mIDH1 AML.

The original version of ivonib has been launched in China, but it is not covered by medical insurance. The price of domestically sold specifications0.25g*60 tablets per box is as high as 100,000 yuan, while the price of the original American version sold overseas is as high as more than 200,000 yuan per box (the price may fluctuate due to exchange rates). Generic drugs of Ivonib are also sold overseas. Their drug ingredients are basically the same as those of the original drugs sold domestically and abroad. For example, the price of 250mg*60 tablets produced by a Laos pharmaceutical factory may be more than 6,000 yuan per box (the price may fluctuate due to the exchange rate), and the price is relatively cheap.