Ivosidenib in IDH1-mutated Clonal Cytopenia of Undetermined Significance

Blood Cancer
Kelly Bolton, MD, PhD
Washington University


Individuals with cytopenia (low blood cell counts) and clonal hematopoiesis (hee-MA-toh-poy-EE-sis), but do not meet the criteria for a hematologic malignancy have an entity called clonal cytopenias of undetermined significance (CCUS). These patients have an 82% chance of developing a hematologic malignancy in 5-years, 95% in 10-years. These CCUS can develop into acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Although the overwhelming majority of patients inevitably develop a hematologic malignancy, there are no established preventative therapies for patients with CCUS. Studies have shown that AML and MDS originate from stem cells carrying pre-leukemic mutations. IDH mutations occur in 19% of AML patients and roughly 5% of patients with MDS. Furthermore, individuals with clonal hematopoiesis containing the IDH mutation are 28 times more likely to develop AML than those without the IDH mutation. Ivosidenib is an FDA-approved drug for relapsed/refractory AML that targets IDH-1. This phase II study will assess if ivosidenib can improve blood cell counts in patients with CCUS who have the IDH1 mutation. If successful, this study would represent the first use of a targeted therapy for the chemoprevention of myeloid neoplasms.

Trial Registration: ClinicalTrials.gov Identifier: NCT05030441