Outcomes of patients with IDH1-mutant relapsed or refractory acute myeloid leukemia receiving ivosidenib who proceeded to hematopoietic stem cell transplant

Abstract

For patients with relapsed/refractory (R/R) acute myeloid leukemia (AML), allogeneic hematopoietic stem cell transplantation (HCT) following salvage therapy is a potentially curative treatment approach [1]. Unfortunately, only a minority of patients are able to obtain a complete remission (CR) in the relapsed setting with standard therapies. Outcomes of patients who transition to HCT after remission induction with mutant isocitrate dehydrogenase 1 (mIDH1) inhibitor monotherapy have not been previously reported. Somatic mutations in the conserved active site of the metabolic enzyme IDH1 are present in ~6−10% of patients with AML [2–4], and lead to the production of the oncometabolite D-2-hydroxyglutarate (2-HG) [5], leading to metabolic dysregulation, epigenetic dysregulation, and impaired cellular differentiation [6, 7]. Ivosidenib (formerly AG-120) is an oral, targeted, small-molecule inhibitor of the mIDH1 enzyme, which effectively suppresses production of 2-HG, and is approved for the treatment of AML with a susceptible IDH1 mutation as detected by a US FDAapproved test in adults with newly diagnosed AML who are aged ≥75 years or who are ineligible for intensive induction chemotherapy, and those with R/R AML. In a phase 1 doseescalation and -expansion study enrolling patients with advanced mIDH1 hematologic malignancies, those with R/ R AML receiving ivosidenib 500 mg once daily (QD) had a CR plus CR with partial hematologic recovery (CRh) rate of 30.2% [8]. CRh was defined as <5% blasts in the bone marrow and partial recovery of peripheral blood counts (platelets >50 × 10/L and absolute neutrophil count >0.5 × 10/L) [8]. Given its favorable safety profile in patients with AML and its clinical efficacy [8], ivosidenib could provide an effective nonintensive treatment strategy for remission induction prior to HCT for patients with mIDH1 R/R AML. Here, we report the characteristics and outcomes for the subgroup of patients with mIDH1 R/R AML from this phase 1 study who received a starting dose of ivosidenib 500 mg QD, responded to ivosidenib treatment, and subsequently underwent allogeneic HCT (n= 17). The detailed study design is reported elsewhere [8]. Briefly, this was a multicenter, open-label, dose-escalation and -expansion study enrolling patients aged ≥18 years with an Eastern Cooperative Oncology Group Performance Status score of * Courtney D. DiNardo [email protected]