MM-205: Clonal Hematopoiesis in Multiple Myeloma, Relations with Treatment Toxicity

Context Multiple myeloma (MM) is a clonal plasma cell neoplasm with a mean age of diagnosis of 68. The main targets in the treatment are immunomodulatory therapies and ASCT. CHIP mutations are common in plasma cell neoplasms. CHIP have been shown to be associated with previous cytotoxic treatment. Objective To detect accompanying somatic mutations, dysplasia, and presence of CHIP in MM patients. To evaluate in terms of treatment-related toxicities (TrTs) in patients with CHIP. Design The data of 45 MM patients who underwent bone marrow biopsy and studied NGS between February 2020 and January 2021 at Trakya University Hospital were retrospectively re-evaluated. Patients or Other Participants The mean age of the patients was 63.67; 24 of the patients were female and 21 were male. Bone marrow biopsy was performed in all patients and NGS was studied. The treatments received by the patients were retrospectively analyzed and recorded. Interventions The patients were diagnosed with MM using the WHO 2016 Myeloid Neoplasm Classification. Somatic mutation results were analyzed by the QIAact Myeloid DNA NGS Panel molecular analysis. Hematologic TrTs National Cancer Institute’s common nomenclature criteria was used for adverse events. Results When the data of 45 MM patients were analyzed, CHIP was detected in 35 patients. Mutational profile showed DNMT3A mutation in 11 patients, TET2 in 13 patients, RAS in 10 patients and other mutations including ASXL1, CSFR3R or RUNX1 in 11 patients. Though anemia is an end organ damage of MM, DNMT3A positivity was related with initial presentation of anemia (p=0.043). Thrombocytopenia was observed at the time of diagnosis in two patients with positive RAS (p=0.006). We found that patients using maintenance lenalidomide or bortezomib after ASCT were associated with the development of anemia in DNMT3A positive patients, but not with the development of anemia in TET2 positive patients. Neutropenia after treatment was observed in 22 patients, and in 20 of these patients, CHIP was present (p=0.039). Anemia after treatment was observed in 32 patients and 27 of these patients had CHIP (p=0.009). Conclusions Patients with CHIP are more prone to develop cytopenia and other toxicities with treatment. Patients cannot receive optimal myeloma treatment by delays or dose reductions in treatment. Investigation of CHIP in MM patients is necessary in treatment planning and follow-up.