Outcomes of patients with IDH1-mutant relapsed or refractory (R/R) AML receiving ivosidenib who proceeded to hematopoietic stem cell transplant (HCT)

Ivosidenib may present a useful treatment option to allow patients with R/R AML to achieve remissions and subsequently proceed to HCT

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HCT following salvage therapy is a potentially curative option in the treatment of patients with R/R AML. However, using standard therapies, few patients with relapsed AML achieve complete remission (CR). Ivosidenib – an oral, reversible, targeted, small-molecule inhibitor of the mutant IDH1 (mIDH1) enzyme – suppresses production of the oncometabolite 2-HG and is currently approved for the treatment of mIDH1 AML in adults with newly-diagnosed AML who are ≥75 years old or who have comorbidities that preclude use of intensive induction chemotherapy, and those with R/R AML.

Based on a previously reported phase I study (NCT02074839),1 we evaluated outcomes in a subgroup of 17 patients with mIDH1 R/R AML who received a starting dose of ivosidenib 500 mg once-daily and subsequently underwent HCT after responding to treatment with ivosidenib. Notably, these patients (median age of 62 years, with common baseline mutations of NPM1, DNMT3A, and SRSF2) had either exhausted standard-of-care salvage therapies or were not suitable candidates.

Prior to HCT, 11 patients achieved a best overall response of complete remission and 6 achieved partial remission (Figure 1). Median overall survival (OS) from start of ivosidenib treatment was 14.5 months (95% CI: 9.1–not estimable). Other key outcomes of this analysis included encouraging overall and relapse-free survival rates of 76.5% and 58.8%, respectively, 6 months post-HCT. We also report data on clearance of mIDH1 in the bone marrow, based on digital PCR. Interestingly, while mIDH1 was undetectable during treatment and prior to HCT in one patient who achieved complete remission, this was not the case for the other patients in this analysis, suggesting that molecular clearance of mIDH1 before HCT was not a necessity for these patients to benefit from HCT.

Figure 1. Swimmer plot of ivosidenib treatment duration, response, and post-HCT follow-up. Partial response included complete remission with incomplete hematologic or platelet recovery and morphologic leukemic-free state. Adapted from the full article (DiNardo CD, et al. Leukemia 2021).

Our results suggest that ivosidenib monotherapy was effective in achieving remission in patients with mIDH1 R/R AML, allowing those who were not previously considered suitable for intensive chemotherapy to proceed to HCT. This is encouraging given that only a minority of such patients are able to obtain a complete remission in the relapsed setting with standard therapies. The role of ivosidenib in post-HCT maintenance is currently being evaluated in a separate ongoing study (NCT03564821). These data are important to confirm that ivosidenib can serve as a successful “bridge” to a potentially curative allogeneic stem cell transplant, for patients with relapsed or refractory AML with IDH1 mutation.


  1. DiNardo CD, Stein EM, de Botton S, Roboz GJ, Altman JK, Mims AS, et al. Durable remissions with ivosidenib in IDH1-mutated relapsed or refractory AML. N Engl J Med. 2018;378:2386–98.

Courtney DiNardo

Associate Professor, MD Anderson