https://orcid.org/0000-0002-6244-1229
Key Points
This prospective international analysis demonstrated a real-world t(11;14) detection rate of 22.1% in patients with MM.
Increased frequency of IRF4 mutations was observed for t(11;14)-positive disease among patients with both NDMM and RRMM.
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 (NCT04721002), 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=0.022) and light-chain only disease (NDMM OR: 3.02, 95% CI: 1.33-6.87; p=0.008). 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.
