Ivosidenib Plus Venetoclax and Azacitidine Safe, Effective in IDH-Mutated Myeloid Malignancies

Treatment with ivosidenib plus venetoclax, with or without azacitidine, had an acceptable safety profile and led to high rates of complete responses in a study of patients with IDH1-mutated myeloid malignancies. Curtis Andrew Lachowiez, MD, from The University of Texas MD Anderson Cancer Center in Houston, shared interim results from this study at the 2021 American Society of Clinical Oncology Annual Meeting.

In this phase Ib/II trial, Dr. Lachowiez and investigators enrolled a total of 25 adults with IDH1-positive malignancies: four with myelodysplastic syndromes (MDS), 13 with newly diagnosed acute myeloid leukemia (AML; including de novo and secondary), and eight with relapsed/refractory AML.

Treatment consisted of 28-day cycles of ivosidenib 500 mg daily (starting on day 14) combined with venetoclax with or without azacitidine at one of three dose levels:

  • DL1: ivosidenib plus venetoclax 400 mg (n=6)
  • DL2: ivosidenib plus venetoclax 800 mg (n=6)
  • DL3: ivosidenib plus venetoclax 400 mg plus azacitidine 75 mg/m2 on days 1-7 (n=13)


The overall response rate after a median follow-up of 16.1 months was 92%, including 67% in group DL1 and 100% in groups DL2 and DL3.

Rates of composite complete response (CRc; including CR with incomplete or complete hematologic recovery) was 84%. The authors noted that rates of CRc were highest in the DL2 and DL3 groups, and in patients with newly diagnosed AML or MDS.

Patients received a median of four treatment cycles, and responses were ongoing at one year in 62% (33% with DL1; 50% with DL2; and 82% with DL3).

Febrile neutropenia and pneumonia were the most common grade 3/4 adverse events reported in the study (28% and 24%, respectively). While two patients experienced tumor lysis syndrome and four experienced differentiation syndrome, the authors noted that all cases resolved with medical management.