IWG 2023, 2006 MDS Criteria Assessments of Ivosidenib for mIDH1 Disease Compared

In a recent study, researchers assessed the clinical performance of ivosidenib for treatment of mutant isocitrate dehydrogenase 1 (mIDH1) myelodysplastic syndrome (MDS) using the International Working Group (IWG) 2023 MDS criteria. Based on these criteria, they found that ivosidenib produced a high overall response rate (ORR) in this setting.

The researchers also used this study to compare the assessments done using the 2023 MDS criteria with those of the 2006 criteria.

“By eliminating [the IWG 2006 marrow complete remission (CR) category] and assessing response in a high-risk population with [less than] 5% blasts, IWG 2023 criteria accurately capture the clinical benefit of ivosidenib in relapsed or refractory MDS,” wrote lead author Yazan Madanat, MD, of the University of Texas Southwestern Medical Center, Dallas.

The researchers presented their findings at the 66th American Society of Hematology Annual Meeting & Exposition in San Diego, California.

The study had a cohort of 19 patients with MDS previously treated with standard-of-care therapy. The patients had a median age of 73 years, and 78.9% had prior hypomethylating therapy. Eighteen patients had efficacy-evaluable data. The cohort received oral ivosidenib 500 mg daily through 28-day cycles.

In their comparison of assessments done with the IWG 2023 versus the 2006 criteria, the investigators’ IWG 2023 assessment applied a composite CR category. This composite CR combined CR with CR equivalent, CR with limited count recovery, and CR with partial hematologic recovery.

According to IWG 2006 criteria, the cohort had a CR plus partial remission (PR) rate of 38.9%, with CR achieved in all responders. By IWG 2023 criteria, the composite CR plus PR rate was 66.7%. By IWG 2006 criteria, the cohort had an ORR of 83.3%, and by IWG 2023 criteria, an ORR of 72.2%

Eight patients who had been classified as having marrow CR by IWG 2006 criteria were reclassified by IWG 2023 criteria as follows: one with CR, four with CR with limited count recovery, one with hematologic improvement, and two with no response. Median time to composite CR was 1.58 months, and median duration was not reached.

Transfusion independence was achieved by five of seven patients who required red blood cell transfusion at baseline and by three of four patients who required platelet transfusion. The median time to either independence type was 2.64 months for patients with composite CR. Ten of 12 patients with composite CR had or maintained transfusion independence during the study. The median duration of transfusion independence was not reached.

“While comparison of survival outcomes between IWG 2006 and IWG 2023 is limited by the small sample size, a similar trend with response-dependent EFS and OS outcomes was observed,” Dr. Madanat concluded.

Reference

Madanat YF, Fathi AT, Garcia-Manero G, et al. Ivosidenib in patients with mutant isocitrate dehydrogenase 1 (mIDH1) relapsed/refractory myelodysplastic syndromes: Update of the phase 1 substudy per the International Working Group 2023 response criteria. Abstract #1841. Presented at the 66th American Society of Hematology Annual Meeting and Exposition; December 7-10, 2024; San Diego, California.