P832: prospective real-world evaluation of the prevalence of t(11;14) in multiple myeloma: third interim analysis from the medici study

Topic: 13. Myeloma and other monoclonal gammopathies - Biology & Translational Research Background: Multiple myeloma (MM) is characterized by bone marrow (BM) infiltration of monoclonal plasma cells (PCs) harboring well-defined genetic aberrations, such as t(11;14). Venetoclax, a highly selective, potent oral BCL-2 inhibitor, has previously shown efficacy in patients (pts) with t(11;14) relapsed/refractory MM (RRMM) and is under investigation as targeted therapy in combination with dexamethasone for t(11;14) RRMM in the randomized phase 3 CANOVA study. Previous studies suggest 15–20% of pts with MM carry t(11;14). However, historical studies may underestimate t(11;14) prevalence as CD138 enrichment of PCs (plasma cell enrichment [PCE]) before fluorescence in situ hybridization (FISH) testing has not been, and currently is not, standard practice globally, despite enhanced t(11;14) detection with this method. MEDICI is an ongoing, global, prospective study evaluating t(11;14) prevalence using interphase FISH with PCE in newly diagnosed MM (NDMM) and RRMM. Aims: To report real-world t(11;14) prevalence based on MEDICI third interim analysis. Methods: The multicenter, non-interventional MEDICI study (NCT04721002) enrolled pts (≥18 years) who provided signed informed consent. BM aspirates were collected at diagnosis and/or disease relapse. Immunomagnetic particles (STEMCELL Technologies) were used to select CD138+ cells, thereby enriching PCs from BM aspirates. Vysis IntelliFISH CCND1/IGH XT FISH probe kit (Abbott) was used to evaluate t(11;14) status by FISH with PCE. The primary objective is to evaluate t(11;14) prevalence in NDMM and RRMM using interphase FISH with PCE, excluding patients who had a failed test. The primary endpoint is t(11;14) status of the earliest BM sample collected at initial diagnosis or across subsequent lines of therapies. Results: At the 16 January 2023 cutoff, 312 pts (NDMM, n=204; RRMM, n=108) were enrolled in 20 countries. Median age was 66 years, and most pts were male (53.5% vs 46.5% female) and Caucasian/White (83.3% vs 10.3% Hispanic/Latino, 2.9% Asian, 1.0% Black/African American, 2.6% unknown). ECOG performance status was ≤2 in 82.7% of pts, >2 in 4.5%, and unknown in 12.8%. Disease was ISS stage I in 30.8% of pts, stage II in 25.6%, stage III in 27.6%, and unknown in 16.0%. FISH testing was evaluable in 295 pts (94.6%), only 6 (2.0%) of whom had an indeterminate result. The observed overall t(11;14) prevalence (95% CI) was 20.7% (16.2–25.8). Prevalence of t(11;14) was 18.7% (13.5–24.8) in pts with NDMM and 24.7% (16.5–34.5) in pts with RRMM. The distribution of t(11;14)-positive pts across lines of therapy was 18.7% (13.5–24.8) in 1L, 20.6% (8.7–37.9) in 2L, and 27.3% (17.0–39.6) in 3L+. The distribution of t(11;14)-positive pts across disease stage was 20.7% (12.9–30.4) in stage I, 19.5% (11.3–30.1) in stage II, and 17.5% (9.9–27.6) in stage III. t(11;14) FISH fusion patterns were consistent between NDMM (1F, 29.7%; 2F, 45.9%; ≥3F, 16.2%) and RRMM (1F, 33.3%; 2F, 45.8%; ≥3F, 16.7%). Available del(17p) testing (evaluable pts: NDMM, 128/204; RRMM, 52/108) showed the highest rate of del(17p) occurred in pts with t(11;14)-positive NDMM (18.9% [7/37]) compared with t(11;14)-negative NDMM (8.8% [14/159]; Table). Available gain(1q) testing (evaluable pts: NDMM, 124/204; RRMM, 38/108) showed the highest rate of gain(1q) occurred in pts with t(11;14) RRMM (29.2% [7/24]) compared with t(11;14)-negative RRMM (10.1% [7/69]). Summary/Conclusion: MEDICI third interim analysis showed an overall t(11;14) prevalence of 20.7% as detected by FISH with PCE. Rates of poor prognostic markers del(17p) and gain(1q) were highest in t(11;14) NDMM and t(11;14) RRMM, respectively.Keywords: Plasma cells, Myeloma, “t(11;14)”