RD Vs. VRD: What Is the First-Line, Real-Life Management of Multiple Myeloma Patients Ineligible for Stem Cell Auto Transplantation in the Emmy Cohort?
Authors: Decaux Olivier , Perrot Aurore , Frenzel Laurent , Royer Bruno , Araujo Carla , Belhadj Karim , Moreau Philippe , Caillot Denis , Leleu Xavier , Farge Agathe , Vekhoff Anne , Schulmann Samantha , Fontan Jean , Orsini Frederique , Sanhes Laurence , Richez Valentine , Jaccard Arnaud , Garlantezec Ronan , Texier Nathalie , Germain Raphael , Boccaccio Catherine , Hulin Cyrille 
Published: November 2021

Abstract
Background
In recent years, large clinical trials have shown the superiority of L1 RD (lenalidomide-dexamethasone) over MPT, and then L1 VRD (lenalidomide, bortezomib and dexamethasone) over RD in Multiple Myeloma (MM) patients ineligible for autologous stem cell transplantation (ASCT). The EMMY study, a large-scale epidemiological study to assess the epidemiology and real-life management of multiple myeloma (MM), describes the real-life use and efficacy of RD and VRD regimens in first-line patients not eligible for ASCT (non ASCT-L1).
Methods
EMMY is a descriptive, multicenter, national, non-interventional study conducted in 72 IFM (Intergroupe Francophone du Myélome, sponsor) centers in France. Any patient initiating treatment for MM over a 3-month observation period, from October to December, is included, since 2017. It is a dynamic cohort with the inclusion of 1000 additional patients each year (2765 patients included at the end of 2019). Data are updated annually from hospital records up to 2020.
The sample of patients receiving RD or VRD therapy in the non ASCT-L1 patient group, over the 2017-2019 period, was extracted to describe patient characteristics. The time to next treatment (TNT), and overall survival (OS) were estimated. The strategies were compared in the subgroup of patients aged of [65-75[ year-old (Wilcoxon test).
Results
Among the 773 EMMY patients initiating a non ASCT-L1 treatment during the period 2017-2019, 162 (21%) received RD and 158 (20%) VRD. The median follow-up was 22 months (RD) and 11 months (VRD). Other patients received MPV (26%, n=204), VCD (13%, n=101), VD (8%, n=61), VTD (5%, n=37) or other combinations (7%, n=50).
Median age was 79.6 [73.7-83.1] and 69.3 [64.7-73.2] years at initiation of RD and VRD. When available, other characteristics were similar between the 2 groups: ECOG ≥ 2 for 31% (RD) (n= 23/ 74) and 26% (VRD) (n=17/65), high cytogenetic risk for 13% (RD) (n=9/67) and 12% (VRD) (n=9/77), ISS at 1/2/3 for 32, 28, and 40% (RD) (n= 83) and 33, 23, and 44% (VRD) (n= 87) of patients. ASCT was initially planned for 23 of 82 patients initiating VRD in late 2019.
The mTNT was 29.1 months 95%IC [20.1-37.7] in RD patients and 34.1 months 95%IC [24.1 - NA] in VRD patients. For patients who received other combinaison in non ASCT-L1, mTTNT varied from 5.2 months 95%IC [3.6 - 12.6] (VRD) and 5.3 months 95%IC [3.9 -15.3] (VD) to 13 months 95%IC [9.2 - 24.7] (VCD), 13 months 95%IC [9.2 - 20.3] (other) and 20.3 months 95%IC [17.2 - 24] (MPV) (p&lt;0.0001).
The mTNT by age (&lt;≥ 75 years) is identical for RD patients: 29.4 95%IC [14.4 - NA] months (n=50) vs 29.5 months [20.1 - NA] (n=112). In VRD patients, mTNT was 34.7 months 95%IC [27.8 - NA] in &lt;75 years under VRD (n=128) vs 17.1 months 95%IC [9.3 - NA] in ≥ 75 years (n=30).
OS at 24 months was 86% [78; 91] and 85% [75; 91] for the RD and VRD groups, respectively. Of the 55 RD patients who relapsed and initiated L2, 46 (84%) received bortezomib (MPV 26%, DVD 16%, VD 18%, and VCD 11%). The 39 VRD patients with initiated L2 received IMID (72%) and/or anti CD38 (50%) in various strategies (DPomDex 17%, DRD 14%, DVD 6%).
By focusing on the [65-75[ year old patient group (n=135, including 48 RD and 87 VRD patients), the 12 and 24 month TTNT rates were respectively 67% [54;85] and 55% [40;71] in the RD group (n=48) vs 85% [77-92] and 71% [58-84] in the VRD group (n=87) (p.0,01). In this subgroup RD patients were slightly older (72 vs 70 year-old) with ECOG≥2 in 41% vs 18%.
Conclusion
RD and VRD stragegies improve TTNT in non ASCT L1 patients. RD is predominantly prescribed to patients ≥75 years of age in whom it remains highly effective. For patients ≥75 years of age, prescription of VRD does not appear to provide significant benefit vs. RD. For those &lt;75 years, a triple VRD combination should be now preferred with a benefit on TNT rates at 12 and 24 months. However, the recent approval of daratumumab in the first-line treatment of patients ineligible for autologous transplantation raises questions about the use of VRD in the first line. Several ongoing studies will give important data about tolerance and efficacy of VRD associated with anti-CD38 therapy.
Figure 1 Figure 1.

Disclosures
Decaux: Amgen BMS Celgene Janssen Sanofi Takeda: Honoraria. Perrot: Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Research Funding; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Honoraria. Moreau: Sanofi: Honoraria; Amgen: Honoraria; Janssen: Honoraria; Abbvie: Honoraria; Celgene BMS: Honoraria; Oncopeptides: Honoraria. Leleu: Roche: Honoraria; Pierre Fabre: Honoraria; Oncopeptides: Honoraria; Novartis: Honoraria; Mundipharma: Honoraria; Merck: Honoraria; Karyopharm Therapeutics: Honoraria; Janssen-Cilag: Honoraria; Gilead Sciences: Honoraria; Celgene: Honoraria; Carsgen Therapeutics Ltd: Honoraria; Bristol-Myers Squibb: Honoraria; Sanofi: Honoraria; Takeda: Honoraria, Other: Non-financial support; Amgen: Honoraria; AbbVie: Honoraria. Sanhes: Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Jaccard: Abbvie: Honoraria; Janssen: Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria. Boccaccio: celgene: Current holder of individual stocks in a privately-held company. Hulin: Celgene/BMS: Honoraria; Janssen: Honoraria; Sanofi: Honoraria; Takeda: Honoraria; abbvie: Honoraria.