Targeting the IL-8 Axis in High-Risk Myelodysplastic Syndromes: a Clinical Experience with Antibody Blockade Combined with Decitabine/cedazuridine.

Clinical and laboratory findings are presented from a 64-year-old female with myelodysplastic syndrome and increased blasts-2 (MDS-IB2) from Phase I/II trial evaluating the anti-IL8 antibody, BMS-986253, in combination with oral decitabine/cedazuridine (NCT05148234). Each 28-day cycle included BMS-986253 1200 mg IV on Day 1 and 15, and oral decitabine/cedazuridine (35 mg/100 mg) on Days 2-7. The patient received 2.5 cycles. Treatment was discontinued on Cycle 3 Day 8 after development of jaw osteonecrosis, deemed unlikely to be treatment related. Despite presenting with high-risk disease, the patient achieved stable disease. Serial bone marrow assessments revealed decreased granulocytes, increased lymphocytes, and reduced CD45 + CD33 + HLA-DR- and CD117 + HLA-DR- cells. Bone marrow plasma multiplex cytokine analysis demonstrated increased inflammatory and immune surveillance proteins. Optical genome mapping identified ETS-related gene, ERG, somatic duplication with post-treatment decreased variant allele frequency. Post-treatment molecular changes with clinical disease stability, suggest IL-8 pathway inhibition biological activity after even short duration.