Abstract
Introduction: Multiple myeloma (MM) is the second most common hematologic malignancy characterized by bone marrow infiltration by monoclonal plasma cells (PC). Several well-defined genetic abnormalities have been identified as relevant with the disease. Although novel therapies have improved overall survival most patients with MM will eventually relapse or become refractory (RR). Therefore, there is an emerging need for better therapeutic regimens including personalized medicine based on specific biomarkers. Venetoclax (Ven) is a selective and potent oral B-cell lymphoma-2 (BCL-2) inhibitor that has shown significant antimyeloma activity in patients with t(11;14) RRMM (Kumar et al. Blood 2017; 130 (22): 2401-2409). In the phase 3 BELLINI (NCT02755597) study, patients with t(11;14) RRMM showed improved response rates and progression-free survival when treated with Ven in combination with bortezomib and dexamethasone compared to placebo-bortezomib-dexamethasone (Kumar et al. Lancet Oncol. 2020; 21:1630-1642). These results suggest that t(11;14)-based selection of patients with MM may represent a potential biomarker for venetoclax-based treatment regimens. An ongoing phase 3 study, CANOVA (NCT03539744), is evaluating the combination of Ven and dexamethasone in patients with t(11;14) RRMM compared to standard of care pomalidomide-dexamethasone (Mateos et al. J Clin Oncol 2020; 38: no. 15_suppl) . Understanding the prevalence of t(11;14) MM in a real-world setting will provide important insights for targeted therapy in this patient subpopulation. Therefore, the MEDICI study was designed to evaluate the real-world prevalence of t(11;14) as detected by interphase fluorescence in situ hybridization (FISH) technology in patients with MM.
Methods: MEDICI (NCT04721002) is an ongoing, prospective, multicenter minimally interventional study. The primary objective is to determine the prevalence of t(11;14) in both newly diagnosed (ND) and RRMM as determined by interphase FISH analysis of monoclonal bone marrow (BM) PCs. All patients (≥18 years) included in the study signed informed consent. BM aspirates (BMA) were collected as part of standard of care procedures performed at diagnosis and disease relapse. Patients with no BMA sample at the time of diagnosis or confirmation of relapse were excluded from the trial. The primary endpoint was the t(11;14) status of the earliest bone marrow sample collected at initial diagnosis or across subsequent lines of therapies. CD138-enriched BMA samples were evaluated for t(11;14) by FISH (Abbott Molecular).
Results: Sixty-two patients were included at the time of the interim analysis (data cut-off 09 March 2022). Median age was 67.5 years, 51.6% were male and 95.2% were Caucasian. Patients with ECOG performance status ≤2/>2/unknown was 83.9%/8.1%/8.1%. ISS stage across patients were stage I (30.6%), stage II (22.6%), stage III (33.9%) and unknown (12.9%) respectively. Del 17p was observed in 6.5% of patients and gain of chromosome 1q in 25.8% of patients.
There were 36 and 26 patients with NDMM and RRMM respectively. One patient had longitudinal samples. The overall prevalence of patients with t(11;14) MM was 30.0%, which was similar between NDMM (25.0%) and RRMM (37.5%) patients (Table). The distribution of patients across the observed t(11;14) FISH fusion (F) categories (1F/2F/≥3F) for NDMM was 33.3%/22.2%/22.2% and 44.4%/55.6%/0.0% in RRMM pts (Table). Across lines (L) of therapy, the distribution of t(11;14)+ patients were similar between 1L (25.0%) , 2L (35.7%), and 3L+ (36.4%) (Table). The distribution of t(11;14)+ patients across disease stage was also similar between stage I (31.6%), stage II (28.6%), and stage III (25.0%) respectively. There were 8 patients with unknown stage of disease, 3 among them were t(11;14)+.
Conclusion: Interim analysis of MEDICI demonstrated that prevalence of t(11;14) was consistent across ND and RRMM setting and independent of line of therapy and disease stage. This study is currently ongoing, and further updates will be provided upon presentation.
Disclosures
Spencer:Haemalogix: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; BMS: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria, Research Funding, Speakers Bureau; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Honoraria. Gavriatopoulou:Karyopharm: Consultancy, Honoraria; GSK: Consultancy, Honoraria; Janssen Cilag: Honoraria; Sanofi: Honoraria; Genesis Pharma: Honoraria; Takeda: Consultancy, Honoraria; Amgen: Consultancy, Honoraria. Coriu:Accord: Consultancy; Genesis pharma: Consultancy. Basic - Kinda:AbbVie: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria. Hajek:Janssen: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; AbbVie: Consultancy; BMS: Consultancy, Honoraria; Norvatis: Consultancy; PharmaMar: Consultancy, Honoraria; Takeda: Consultancy, Honoraria. Pahwa:ICON plc: Current Employment; AbbVie: Other: AbbVie funded ICON for this study. Taylor:AbbVie: Current Employment, Current equity holder in publicly-traded company. Lehn:AbbVie: Current Employment, Current equity holder in publicly-traded company. Joehanes:AbbVie: Current Employment, Current equity holder in publicly-traded company. Ross:AbbVie: Current Employment, Current equity holder in publicly-traded company. Hader:AbbVie: Current Employment, Current equity holder in publicly-traded company.
OffLabel Disclosure:
Venetoclax is a BCL-2 inhibitor that is FDA approved for multiple indications. Venetoclax is not currently approved for the treatment of multiple myeloma.
