Real-World Clinical Outcomes of Multiple Myeloma Patients with High-Risk Cytogenetics Treated with Dararvd, Single Center Experience

Background: As per International Myeloma Working Group Consensus, t(4;14), del 17p, t(14;16), t(14;20), deletion 1p and gain 1q are considered high risk cytogenetic abnormalities (HR CA) and carry poor prognosis. In the phase 2 Griffin trial, Daratumumab (Dara) combined with Lenalidomide (Revlimid®,R) Bortezomib (Velcade®,V) and Dexamethasone (D) (DaraRVD) showed improved rates of stringent complete response (sCR) and minimal residual disease (MRD) negativity that led to its inclusion as "other recommended regimen" in National Comprehensive Cancer Network guidelines. We explored progression free survival (PFS), Overall survival (OS) and MRD negativity rate of patients with HR CA who received frontline DaraRVD vs standard of care (SOC) in a real-world setting.

METHODS: This is a single center, retrospective study that included a total of 149 myeloma patients with HR CA who were treated with induction SOC n=121 or DaraRVD n=27, from 2010 to February 1 2022 at a tertiary cancer center. SOC regimens that were included in our study consisted of: Revlimid® Velcade® Dexamethasone (RVD), Cyclophosphamide VD, Carfilzomib RD (KRD), Carfilzomib Pomalidomide Dexamethasone (KPD). Primary analysis compared the PFS between DaraRVD and SOC group using the log-rank test. Secondary analyses compared OS and MRD negativity rates between the two groups using the log-rank and Fisher's exact tests, respectively. MRD negativity was assessed by flow cytometry (sensitivity 10^-5) at the end of induction treatment

Results: Demographic and clinical characteristics were well balanced in both groups (Table1). The 1 year and 2year progression free survival rates were 0.91 (95% CI 0.67,0.98) and 0.91 (0.67,0.98) in the DaraRVD group and superior to 0.84 (95% CI 0.77,0.90) and 0.71 (95% CI 0.62,0.79), respectively in the SOC group, without reaching statistical significance (p=0.11) (Figure 1a). The 1year and 2year overall survival rates were 0.95 (95% CI 0.68,0.99) and 0.87 (95% CI 0.58,0.97) in the DaraVRD group and again superior to that of SOC group with 0.87 (95% CI 0.79,0.91) and 0.79 (95% CI 0.71,0.85), respectively (p=0.17) (Figure 1b). The MRD negativity rates were similar in both groups with 40% for DaraRVD and 39.5% for SOC respectively (p=0.89)

Conclusion: In patients with high risk cytogenetics, frontline treatment with DaraRVD showed a trend towards superior PFS and OS with a similar MRD negativity rate compared to SOC in real world setting. Larger prospective studies are ongoing to evaluate efficacy of quadruplet therapy in patients with high risk cytogenetics

McCarthy:Axios: Consultancy, Honoraria; Magenta Therapeutics: Consultancy, Honoraria; Fate Therapeutics: Consultancy, Honoraria; Bluebird Bio: Consultancy, Honoraria; Takeda Pharmaceuticals America, Inc.: Consultancy, Honoraria; Partner Therapeutics, Inc.: Consultancy, Honoraria; Oncopeptides: Consultancy, Honoraria; Karyopharm Therapeutics Inc.: Consultancy, Honoraria; Sanofi: Consultancy; Janssen Global Services, LLC: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Starton Therapeutics: Consultancy, Honoraria; Juno: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Genentech: Consultancy, Honoraria; Bristol Myers Squibb Company: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Consultancy, Honoraria. Hillengass:Adaptive: Honoraria; Amgen: Honoraria; Axxess Network: Membership on an entity's Board of Directors or advisory committees; Beigene: Honoraria; Beijing Life Oasis Public Service Center: Honoraria; Beijing Medical Award Foundation: Honoraria; BMS: Membership on an entity's Board of Directors or advisory committees; Curio Science: Honoraria; GSK: Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: DSMB; Oncopeptides: Membership on an entity's Board of Directors or advisory committees; Oncotracker: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Skyline: Membership on an entity's Board of Directors or advisory committees.