Prospective real-world evaluation of t(11;14) prevalence and disease biology in multiple myeloma: MEDICI study analysis.

Genetic abnormalities in multiple myeloma (MM) influence treatment outcomes and may inform therapeutic decisions. The most common chromosomal translocation in MM is t(11;14); however, its role in disease progression is not well defined. We report results from MEDICI, a global, minimally invasive, prospective study evaluating t(11;14) status in newly diagnosed MM (NDMM) and relapsed/refractory MM (RRMM). MEDICI enrolled adult patients (≥18 years) with MM with bone marrow (BM) aspirates collected at diagnosis and/or disease relapse. The primary objective was to determine t(11;14) prevalence in patient BM samples using fluorescent in situ hybridization (FISH) with plasma cell enrichment. Samples from 525 patients (NDMM, n = 306; RRMM, n = 219) were analyzed for t(11;14), with 498 patients (95%) having successful BM FISH test. Prevalence of t(11;14) was 22.1% (110/498 patients; 95% confidence interval [CI], 18.5-26.0) in the overall patient population, 18.8% (56/298 patients; 95% CI, 14.5-23.7) in NDMM, and 27.0% (54/200 patients; 95% CI, 21.0-33.7) in RRMM. Patients with t(11;14)-positive MM were evenly distributed across disease stages (stage I, 24.1%; stage II, 20%; stage III, 21.3%); however, higher rates were observed in African American patients (RRMM odds ratio [OR], 7.27, 95% CI, 1.33-39.83; P = .022) and light-chain only disease (NDMM OR, 3.02, 95% CI, 1.33-6.87; P = .008). Chromosome 1q abnormalities occurred more often in the absence of t(11;14); however, higher frequency of mutation in the plasma cell differentiation regulator IRF4 was detected in t(11;14) presence. In conclusion, the results from MEDICI demonstrated reproducible t(11;14) detection with a real-world prevalence of 22.1% in MM. This trial was registered at www.ClinicalTrials.gov as #NCT04721002.