Ivosidenib Plus Venetoclax Regimen Improves Outcomes in IDH1-Mutant Acute Myeloid Leukemia


Among all the treatment arms in the study, the composite complete response rate was 78% and 100% for those who were treatment-naïve for patients treated with the combination of ivosidenib and venetoclax with or without azacitidine in a phase 1b/2 study.

The combination of ivosidenib (Tibsovo) and venetoclax (Venclexta) with or without azacitidine (Vidaza)was both highly effective and well-tolerated as treatment of patients with acute myeloid leukemia (AML) who are IDH1-mutant, according to data from a phase 1b/2 clinical trial (NCT03471260) presented at the 2020 American Society of Clinical Oncology (ASCO) Virtual Scientific Program.1

Among all the treatment arms in the study, the composite complete response (CR) rate was 78% and 100% for those who were treatment-naïve. The compositive CR rate among patients with relapsed/refractory disease was 75%. Investigators also noted that 50% of the patients who achieved a CR were negative for minimal residual disease (MRD).

“This trial is the manifestation of remarkable basic and translational work that is resulting in improved clinical outcomes for patients,” said Curtis Lachowiez, MD, the lead study author and hematology fellow at The University of Texas MD Anderson Cancer Center, in a press release. “The triplet combination may ultimately result in a new, effective therapeutic regimen. As the median age at AML diagnosis is 68, these findings are particularly important for older AML patients who may not be fit enough to receive the aggressive cytotoxic chemotherapy regimens historically used to treat AML.”

Patients with IDH1-mutant myeloid malignancies were enrolled to 1 of the 3 cohorts on the study. In cohort 1, patients received ivosidenib plus venetoclax at 400 mg, while cohort 2 received the same regimen with a higher dose of venetoclax at 800 mg. Cohort 3 received ivosidenib, 400 mg of venetoclax, and azacitidine. The primary end points include safety and tolerability and overall response rate (ORR), while secondary end points included survival end points and pharmacokinetic correlates.2

Overall, 19 patients had enrolled to the study, which included 9 patients with relapsed/refractory AML who had a median of 1 prior line of therapy, 5 patients with treatment-naïve AML, 3 patients with hypomethylating agent-failure myelodysplastic syndrome (MDS) with secondary AML, and 2 patients with high-risk MDS. Eighteen patients were evaluable for analysis.

The ORR was 89% among all patients in the analysis. Four of 6 patients in cohort 1 had an objective response, which included 3 CRs and 1 CR with incomplete blood count recovery (CRi). In cohort 2, all 6 patients had an objective response, including 3 CRs, 2 CR with partial hematologic recovery (CRh), and 1 CRi. All 6 patients in cohort 3 had an objective response, including 1 CR, 1 CRh, 2 CRis, 1 morphologic leukemia-free state (MLFS), and 1 HR.

The median time to best response was 2 months in the overall population. One patient had human immunodeficiency without a CR, and 1 patient had MLFS. Nine patients (50%) remained in study, 3 (17%) proceeded to stem cell transplantation, 5 (22%) expressive progressive disease following a composite CR, and 2 were non-responders after a median of 3 months.

The median overall survival had not been reached in the treatment-naïve group and was 9.7 months in the relapsed/refractory population at a median of 3.5 months of follow-up.

The combination of venetoclax and azacitidine has been previously established as a well-tolerated and effective regimen for newly diagnosed patients with AML, and the IDH inhibitor ivosidenib alone has been approved for the treatment of patients with IDH1-mutated AML. This targeted therapy appears to be a well-tolerated oral therapy for patients that can interrupt the leukemogenic process.1

The purpose of this study was to evaluate the safety, tolerability, and response rate of adding ivosidenib to either venetoclax alone or in combination with azacitidine to treat patients with AML who harbor the IDH1mutation. This trial is continuing to accrue patients.

“This study is exciting because it displays that we are able to tailor therapy for AML patients based on their molecular profile,” stated Lachowiez. “While some mutations have traditionally been associated with poor outcomes, we can now identify certain subgroups of patients with genetic mutations who are more likely to respond to a specific therapy, and then we can design a treatment and follow-up plan to best suit them.”


  1. Combination therapy well-tolerated and highly effective for patients with IDH1-mutated acute myeloid leukemia (AML). News release. MD Anderson Cancer Center; May 28, 2020. Accessed May 29, 2020. https://bit.ly/2XF1Wly.
  2. Lachowiez CA, Borthakur G, Loghavi S, et al. Phase Ib/II study of the IDH1-mutant inhibitor ivosidenib with the BCL2 inhibitor venetoclax +/- azacitidine in IDH1-mutated hematologic malignancies. Presented at: 2020 ASCO Virtual Scientific Program; May 29, 2020. Abstract 7500.

Related Videos
Related Content