An evaluation of c-myc aberrations in patients with newly diagnosed multiple myeloma (NDMM).

Abstract

e20006 Background: Multiple myeloma (MM) is a plasma cell dyscrasia marked by clonal evolution and preceded by a premalignant stage, which progresses via pathway deregulation, including MYC activation. Activation of MYC, an oncogenic protein that is part of the MAP kinase growth and proliferation pathway, has been implicated in the progression to active multiple myeloma. Methods: We performed a retrospective review of clinical features of patients with NDMM and myc aberrations between Oct 2015 and Nov 2017. c-myc abnormalities were found on diagnostic bone marrow evaluations in 19 patients by conventional karyotype and/or fluorescent in situ hybridization assays. Results: 10 (53%) of these patients had a myc 8;14 translocation, 5 (26%) had an overexpression of myc, and 4 (21%) had an underexpression of myc, with a laboratory cutoff for expression at 4% for each of these mutations. 14 (76%) of patients were under 65 years, whereas 5 (24%) of patients were 65 years or older. Evaluation of CRAB features in these myc-mutated newly diagnosed MM patients were as follows: 5 (26%) presented with renal disease (Cr > 2mg/dL); 5 (26%) with hypercalcemia (Ca > 11mg/dL); 16 (84%) with osteolytic lesions found on radiography; 11 (58%) with anemia (Hgb < 10g/dL). This is consistent with previous data of presenting symptoms in NDMM. R-ISS staging for c-myc mutated NDMM patients included: 3 (16%) Stage I; 9 (47%) Stage II, 4 (21%) Stage III, and 3 (16%) with missing staging data. Conclusions: These data suggest that the presence of a myc mutation is not explicitly associated with features thought to otherwise confer a poor prognosis including high-risk cytogenetics, high beta 2 microglobulin, high LDH, and decreased albumin. Further evaluation is necessary to confirm these findings in a larger group of patients and to evaluate the apparent age discrepancy noted in this small retrospective study. Characteristics No. of Patients (N = 19) Percent of Patients (%) Male 10 53% Female 9 47% Age < 65 14 74% Age ≥ 65 5 26% White 8 42% Black 3 16% Asian 1 5% Other 7 37% R-ISS Stage I 3 16% R-ISS Stage II 9 47% R-ISS Stage III 4 21% R-ISS Missing 3 16% Hypercalcemia (Ca > 11mg/dL) 5 26% Renal Disease (Cr > 2mg/dL) 5 26% Anemia (Hgb < 10g/dL) 11 58% Radiographic Osteolytic Lesions 16 84%