IDH-1 Somatic Mutations Are More Commonly Observed Among Patients with Concomitant Myelodysplastic Syndromes (MDS) and Autoimmune Rheumatoid Diseases (AIRD)

Introduction

We previously reported that autoimmune diseases (AID) are commonly observed in MDS patients (pts) (28%) including autoimmune rheumatic diseases (AIRD). There is increase recognition of the association of certain acquired somatic mutations and inflammation. Recent study reported enrichment of AIRD among chronic myeloid neoplasms (MN) pts with high prevalence of IDH mutations suggestive causative association particularly between IDH mutations and seronegative rheumatoid arthritis (Hong et al, Blood 2024). Here, we compare the genomic landscape of MDS pts with concomitant defined AIRD to those without.

Methods

We identified MDS pts with concomitant AIRD. We selected Rheumatoid arthritis (RA) and systemic lupus (SLE) as AIRD given more objective diagnostic criteria and accurate data capturing. We compared those MDS pts with AIRD to MDS pts without.

Results

We compared 79 MDS pts with AIRD to 2469 MDS pts without in our database. AIRD were more observed among female MDS pts compared to non-AIRD MDS pts (59% vs 32%, p < 0.0005). There was no difference in age, race, t-MDS, WHO 2022 classification, IPSS-M risk stratification. There was no difference in baseline myeloblasts% or blood counts.

Among 21 common somatic mutations tested, IDH-1 somatic mutation was the only mutation observed more among AIRD MDS pts compared to non-AIRD MDS pts (11% vs 3%, p <0.0005). Among male AIRD MDS pts rate of IDH-1 was 15% vs 3% and 8% vs 3% among females AIRD MDS pts compared to non-AIRD MDS pts. (p <.0005)

There was no difference among AIRD- MDS pts and non-AIRD MDS pts in median overall survival. There was a non-statistically significant trend for worse median OS among AIRD MDS pts with IDH-1 mutation (30 mo vs 40 mo).

Conclusions

Our data confirm recently reported observation that IDH-1 somatic mutations are enriched among myeloid neoplasms patients with AIRD. Further studies to explore the underlying mechanism, and potential therapeutic implications with targeted IDH-1 inhibitors are warranted.

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