IDH-1 Mutation Linked to Autoimmune Rheumatoid Disease in MDS

Patients with myelodysplastic syndromes (MDS) and concomitant autoimmune rheumatoid diseases (AIRD) showed an increased prevalence of IDH-1 somatic mutations according to a recent study. This finding may pave the way for potential targeted therapeutic strategies.

Increasing evidence suggests a connection between acquired somatic mutations and inflammatory processes in myeloid neoplasms. Rami S. Komrokji, MD, Moffitt Cancer Center, Tampa, Florida, presented a retrospective analysis comparing the genomic landscape of patients with MDS and AIRD with that of patients with MDS without defined AIRD (eg, lupus or rheumatoid arthritis).¹ The retrospective study included 2,548 patients from a robust database, 79 patients with MDS plus AIRD and 2,469 patients with MDS without AIRD.

AIRD was more common among female patients with MDS (59% vs 32%; P<.0005). Other demographic and clinical characteristics—including age, race, and risk stratification—were similar between the groups. The researchers evaluated 21 common somatic mutations, identifying IDH-1 as the sole mutation significantly enriched in the AIRD cohort (11% vs 3%; P<.0005).

When stratified by sex, the prevalence of IDH-1 mutations was 15% in male patients with AIRD MDS compared with 3% in male patients without AIRD and 8% versus 3% among female patients with and without AIRD, respectively. Although no significant differences in median overall survival were noted between the groups with and without, overall survival tended to be lower in patients with AIRD harboring IDH-1 mutations (30 months vs 40 months).

Dr. Komrokji concluded: “Our data confirm recently reported observations that IDH-1 somatic mutations are enriched among myeloid neoplasm patients with AIRD. Further studies to explore the underlying mechanisms and potential therapeutic implications with targeted IDH-1 inhibitors are warranted.”

Reference

1. Komrokji RS, Al Ali NH, Xie Z, et al. IDH-1 somatic mutations are more commonly observed among patients with concomitant myelodysplastic syndromes (MDS) and autoimmune rheumatoid diseases (AIRD). Abstract #3228. Presented at the American Society of Hematology Annual Meeting; December 7-10, 2024; San Diego, California.