Efficacy of D-RVD Vs RVD Among t(11;14) Patients with Newly Diagnosed Myeloma

Introduction: The combination of lenalidomide, bortezomib, and dexamethasone (RVD) is highly effective for newly diagnosed myeloma (NDMM) patients including standard and high risk patients. The addition of daratumumab (dara) to RVD (D-RVD) has been shown to increase deep responses and improve PFS. Phase 3 studies are ongoing to confirm that benefit. We and others have previously demonstrated that patients with t(11;14) have a decreased PFS compared to other standard risk patients. It is unknown whether patients with t(11;14) derive similar benefit from the addition of daratumumab to RVD as part of induction. Here, we present a real-world comparison of consecutively treated patients with t(11;14) with either D-RVD or RVD induction therapy in terms of response and outcomes.

Methods: Of the 1000 consecutive NDMM patients treated with RVD between January 2007- August 2016, and 326 NDMM patients treated with D-RVD induction therapy from April 2018 - August 2022, 185 had t(11;14). 121 were in the RVD cohort and 64 were in the D-RVD cohort. Demographic and clinical characteristics and outcomes data were obtained from our institutional review board approved myeloma database and with manual abstraction. Dara was administered as part of standard RVD induction prior to autologous transplant without planned dara during lenalidomide maintenance. Consolidation after transplant was not planned for either cohort. The responses and progression were evaluated per International Myeloma Working Group Uniform Response Criteria.

Results: Patient characteristics were similar between the two cohorts. The median age was 63 years old. There were 58.7% and 54.7% males in RVD and D-RVD respectively. There were 45.5% and 36.5% black patients in the RVD and D-RVD cohorts respectively. Patients had free light chain only disease in 27.4% and 32.3%. There were 5.3 and 4% R-ISS stage 3 patients. The VGPR rate or better after induction improved from 49.2 to 81.3 with the addition of dara. After transplant, the VGPR rate or better improved from 76.3 to 94.2% with the addition of dara as part of induction. Median PFS for the RVD cohort is 47.3 months (95% CI 35.9 - 58.8) and not reached in the D-RVD cohort (see Figure 1). The median OS for the RVD cohort is 115 months (95% CI 97-133.2) and not reached with 96.9% of the patients alive at last follow up in the D-RVD cohort.

Conclusions: Patients with t(11;14) represent a unique set of myeloma patients with a distinct clinical presentation, biology and response to treatment. These patients have a decreased PFS when compared to other standard risk patient when treated with RVD. Overall survival is similar possibly due to advances in the management of relapsed disease in t(11;14) patients. In this cohort of patients, the addition of dara to RVD improved VGPR rates and PFS. Whether dara is able to completely overcome the PFS disadvantage to t(11;14) will be evaluated with longer follow up.