|The following article features coverage from the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.|
Combination ivosidenib and venetoclax, with or without azacitidine, is effective in patients with IDH1-mutated myeloid malignancies, according to study results presented at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting.
Investigators presented results from a phase 1b/2 study (ClinicalTrial.gov Identifier: NCT03471260) of ivosidenib plus venetoclax, with or without azacitidine.
Patients were 18 years of age and older with IDH1-positive myelodysplastic syndromes (MDS), myeloproliferative neoplasms (MPNs), newly diagnosed acute myeloid leukemia (AML), or relapsed/refractory AML. Newly diagnosed AML included patients with treatment-naive AML and secondary AML.
Patients received ivosidenib plus venetoclax at 400 mg (dose level 1), ivosidenib plus venetoclax at 800 mg (dose level 2), or ivosidenib plus venetoclax at 400 mg in combination with azacitidine (dose level 3).
The analysis included 25 evaluable patients — 6 treated at dose level 1, 6 at dose level 2, and 13 at dose level 3. The patients’ median age was 67 years (range, 44-84 years).
Most patients (n = 21) had AML — 8 with treatment-naïve AML, 5 with secondary AML, and 8 with relapsed/refractory AML. Four patients had MDS/MPNs. Roughly half of patients (52%) had adverse-risk disease, 20% had intermediate-risk disease, and 28% had favorable-risk disease by European Leukemia Net standards.
The overall response rate was 67% for patients treated at dose level 1 and 100% for patients treated at dose level 2 and dose level 3.
The composite complete response (CR) rate (defined as CR plus CR with incomplete blood count/hematologic recovery) was 67% with dose level 1, 100% with dose level 2, and 85% with dose level 3.
The 1-year overall survival (OS) rate was 71% for the entire cohort, 50% with dose level 1, 67% with dose level 2, and 83% with dose level 3.
The 1-year OS rate was 76% for newly diagnosed AML, 50% for relapsed/refractory AML, and 100% for MDS/MPNs.
Minimal residual disease (MRD) negativity was associated with improvement in OS among AML patients. The 1-year OS rate was 100% in MRD-negative patients and 33% in MRD-positive patients (P =.0052).
The most common serious events were febrile neutropenia (28%), pneumonia (28%), and pyrexia (28%). Tumor lysis syndrome occurred in 8% of patients. IDH differentiation syndrome occurred in 4 patients (2 in dose level 1, 1 in dose level 2, and 1 in dose level 3).
Based on these results, the investigators concluded that ivosidenib plus venetoclax, with or without azacitidine, is associated with an acceptable and expected toxicity profile as well as notable efficacy.
Disclosures: This research was supported by MD Anderson Cancer Center and the National Cancer Institute. Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
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Lachowiez CA, Borthakur G, Loghavi S, et al. A phase Ib/II study of ivosidenib with venetoclax +/- azacitidine in IDH1-mutated myeloid malignancies. J Clin Oncol. 2021;39:(suppl 15; abstr 7012). doi:10.1200/JCO.2021.39.15_suppl.7012