Ivosidenib (IVO) prior to hematopoietic cell transplant for patients with IDH1-mutant relapsed or refractory acute myeloid leukemia (R/R AML).

Abstract

7521 Background: Allogeneic hematopoietic cell transplantation (HCT) provides a potentially curative option for patients (pts) with R/R AML. Disease status at the time of transplant is a major determinant of long-term prognosis, with pts typically receiving salvage chemotherapy prior to HCT to induce a remission. However, older and/or heavily pre-treated pts frequently cannot tolerate intensive chemotherapy (IC) or do not obtain adequate disease control to permit an HCT. IVO is an oral, potent, targeted inhibitor of mutant IDH1 (mIDH1) approved for the treatment of adults with newly diagnosed AML ≥75 y of age or ineligible for IC, and those with R/R AML. We assessed HCT outcomes in pts with m IDH1 R/R AML who proceeded to HCT after treatment with IVO in a phase I study (NCT02074839). Methods: Baseline characteristics, clinical response (including CR, CRi/CRp, MLFS), and overall survival (OS) for the subgroup of pts with m IDH1 R/R AML who received IVO 500 mg QD, responded to treatment and then underwent HCT are reported. m IDH1 variant allele frequency (VAF) from bone marrow mononuclear cells was assessed using BEAMing digital PCR (0.02–0.04% VAF detection limit). Results: Among 179 pts with R/R AML treated with IVO, 18 proceeded to HCT: median age, 61.5 y (range 36–68); 56% male; 16.7% had secondary AML; 27.8% had ≥3 prior regimens; 11.1% had a prior HCT. The median duration of IVO treatment prior to HCT was 3.9 mo (range 2.1–15.2). The last reported response prior to HCT was 50.0% CR. Six- and 12-mo post-HCT survival rates were 77.8% and 50.0%; median relapse-free survival post HCT was 7.3 mo (range 2.6–NE). Median OS from start of IVO was 16.8 mo (95% CI 9.2, NE) for HCT pts vs 9.0 mo (95% CI 7.1, 10.2) in the entire study cohort; median follow-up time, 33.2 mo (range 3.2–41.9). Eight HCT pts were censored for OS: 5 are in remission, 2 relapsed and are in survival follow-up, and 1 was lost to follow-up. Median OS was not estimable (95% CI 9.1, NE) for the 12 HCT pts who achieved CR after IVO therapy and was 20.5 mo (95% CI 16.4, NE) for the 31 CR pts who did not undergo HCT. m IDH1 was undetectable in 1/18 (6%) pts; 4/18 (22%) pts had reduction below 1% VAF in ≥1 at the last assessment prior to HCT. Conclusions: IVO monotherapy is a putative treatment option to induce remissions prior to HCT for m IDH1 R/R AML pts who are not considered candidates for intensive salvage therapy. Post-transplant survival rates are encouraging and warrant further investigation of IVO monotherapy or combination salvage therapies prior to HCT. Clinical trial information: NCT02074839 .