The combination of CPX-351and ivosidenib showed “acceptable safety and high efficacy” for patients with newly diagnosed or relapsed or refractory IDH1-mutated acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS), according to interim data of a phase II trial.
The preliminary findings were presented by Jennifer Croden, MD, of the University of Texas MD Anderson Cancer Center, at the 66th American Society of Hematology Annual Meeting & Exposition.
The analysis included 11 response-eligible patients (median age, 57 years; range, 45–72) with IDH1-mutated AML or high-risk MDS. Four had newly diagnosed disease (group A), and seven had relapsed or refractory disease (group B).
In group B, the median number of prior lines of therapy was three (range, 1–4), five patients (71%) had received a hypomethylating agent, seven (100%) had received venetoclax, and two (29%) had received a hematopoietic stem cell transplant (HSCT).
In group A, the overall response rate (ORR) was 100% (n=4), including one complete response (CR), two CR with incomplete count recovery (CRi), and one morphologic leukemia-free state. The median duration of response was 16.3 months; median event-free survival (EFS) was 17.5 months; and median overall survival (OS) was 29.3 months. All four patients also had negative measurable residual disease (MRD) status as evaluated by flow cytometry.
In group B, the ORR was 43% (n=3), including one CR and two CRi. The median EFS was 4.2 months, and median OS was 12.0 months. Four responding patients proceeded to HSCT, of which three remained in remission; one newly diagnosed patient (group A) had a relapse at 17.5 months after transplant. All three responding patients reportedly achieved negative MRD status.
Nine of 11 (89%) patients had IHD1 variant allele frequency (VAF) measured, with eight showing decreases in VAF and six achieving undetectable VAF.
“Interim results suggest acceptable safety and high efficacy of CPX-351 in combination with ivosidenib in newly diagnosed or relapsed or refractory IDH1-mutated AML,” Dr. Croden and colleagues suggested.
Reference
Croden J, Hammond D, Chien KS, et al. Interim results of the phase II study investigating CPX-351 in combination with ivosidenib for patients with IDH1-mutated acute myeloid leukemia and high-risk myelodysplastic syndrome. Abstract #4271. Presented at the 66th American Society of Hematology Annual Meeting & Exposition; December 7-10, 2024; San Diego, California.