Durable response to ivosidenib in post-transplant relapse and leukemic transformation of myelodysplastic syndrome with new complex karyotype and IDH1 R132C mutation.

A 75-year-old man underwent allogeneic hematopoietic stem cell transplantation from a female donor for myelodysplastic syndrome with 7% marrow blasts and 46,XY karyotype. Cytopenias recurred after 9 months. Marrow had <5% blasts, but a 47,XY,t(2;11)(q21;q23),t(2;12)(q13;q21),+mar[9]//46,XX[11] karyotype and a new IDH1 R132C mutation, variant allele frequency (VAF) 8%. Blasts increased, with 24% IDH1 R132C VAF. The IDH1 inhibitor ivosidenib was initiated. Blood and marrow normalized, with 46,XX karyotype and 100% donor engraftment. Blood counts remain normal 14 months after starting ivosidenib. Serial molecular studies identified a new mutation at transplant relapse enabling successful targeted therapy in this otherwise dismal clinical setting.