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

Komrokji, Rami

Oral and Poster Abstracts
637. Myelodysplastic Syndromes: Clinical and Epidemiological: Poster II

Research, MDS, Clinical Research, Genomics, Chronic Myeloid Malignancies, Diseases, Real-world evidence, Myeloid Malignancies, Biological Processes, Human

Rami S. Komrokji, MD¹, Najla H. Al Ali, Ms²^*, Zhuoer Xie, MD, MS³, Zena Komrokji¹^*, Joseph E. Jabbour⁴^*, Onyee Chan, MD⁵, Seongseok Yun, MD, PhD¹, Andrew T. Kuykendall, MD¹, Alison R. Walker, MD, MBA, MPH¹, Jeffrey E Lancet, MD¹, Eric Padron, MD¹ and David Sallman, MD⁶

¹Department of Malignant Hematology, Moffitt Cancer Center, Tampa, FL
²Department of Malignant Hematology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL
³Department of Malignant Hematology, Moffitt Cancer Center, Lutz, FL
⁴Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
⁵H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL
⁶Moffitt Cancer Center and Research Institute, Tampa, FL

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.

Disclosures: Komrokji: BMS: Research Funding; Taiho: Membership on an entity's Board of Directors or advisory committees; PharmaEssentia: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Servio: Honoraria; Celgene/BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Geron: Consultancy, Membership on an entity's Board of Directors or advisory committees; Servier: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; CTI biopharma: Membership on an entity's Board of Directors or advisory committees; Sobi: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Rigel: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Genentech: Consultancy; Keros: Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy; DSI: Honoraria, Membership on an entity's Board of Directors or advisory committees; DSI: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sumitomo Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees; Servio: Membership on an entity's Board of Directors or advisory committees. Chan: Abbvie: Honoraria, Research Funding; Novartis: Honoraria; Syndax: Membership on an entity's Board of Directors or advisory committees; Jazz: Research Funding; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Aptitude Health: Honoraria. Kuykendall: Protagonist Therapeutics: Honoraria, Research Funding; Novartis: Research Funding; Incyte: Honoraria; PharmaEssentia: Honoraria. Lancet: Bristol Myers Squibb: Consultancy, Other: Consultant/Advisory Board; Prelude Therapeutics: Consultancy, Other: Bristol Myers Squibb; Tradewell Therapeutics: Consultancy, Other: Consultant/Advisory Board. Sallman: Abbvie: Consultancy; Agios: Consultancy; Axiom: Consultancy; Gilead: Consultancy; Celyad: Consultancy; Froghorn: Consultancy; Incyte: Consultancy; Intellisphere, LLC: Consultancy; Johnson & Johnson: Consultancy; Kite: Consultancy, Membership on an entity's Board of Directors or advisory committees; Magenta Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees; NextTech: Consultancy; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; AvenCell: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees; BlueBird Bio: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Dark Blue Therapeutics: Membership on an entity's Board of Directors or advisory committees; Intellia: Membership on an entity's Board of Directors or advisory committees; Jasper Therapeutics: Membership on an entity's Board of Directors or advisory committees; NKARTA: Membership on an entity's Board of Directors or advisory committees; Orbital Therapeutics: Membership on an entity's Board of Directors or advisory committees; Rigel Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Shattuck Labs: Membership on an entity's Board of Directors or advisory committees; Servier: Membership on an entity's Board of Directors or advisory committees; Syndax: Membership on an entity's Board of Directors or advisory committees; Syros: Membership on an entity's Board of Directors or advisory committees; Apera: Research Funding; Jazz: Research Funding.

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^*signifies non-member of ASH

3228 IDH-1 Somatic Mutations Are More Commonly Observed Among Patients with Concomitant Myelodysplastic Syndromes (MDS) and Autoimmune Rheumatoid Diseases (AIRD)