Real-World Characteristics and Treatment Patterns of Transplant-Eligible Patients with Newly Diagnosed Multiple Myeloma Treated with Daratumumab, Bortezomib, Lenalidomide, and Dexamethasone (DVRd) As Front-Line Treatment: Results from a Multicenter Chart Review Study
Authors: Tan Carlyn Rose , Gordan Lucio , Dileo Rachel , Mewawalla Prerna , Larson Sarah M. , Davies Faith E , Oveisi David , Gupta-Werner Niodita , Medhekar Rohan , Cortoos Annelore , Armoon Marjohn , Rahman Alvi , Vanden Eynde Claire , Lafeuille Marie-Hélène , Reitan John , Milkovitch Gary , Bubalo Joseph , Forman Adam , Sborov Douglas W , Kaila Shuchita , Usmani Saad Z. 
Published: December 2024

Introduction: The treatment paradigm for transplant-eligible (TE) patients (pts) with newly diagnosed multiple myeloma (NDMM) is shifting from frontline (FL) triplet (e.g., bortezomib [V], lenalidomide [R], and dexamethasone [d]) towards FL quadruplet regimens based on the pivotal PERSEUS and GRIFFIN trials, which showed that addition of daratumumab (D) to VRd during induction/consolidation followed by DR maintenance improved response as well as progression-free survival compared to VRd followed by R maintenance. In the real world, pt characteristics and treatment patterns, including maintenance therapy selection, may differ from clinical trial protocols. Therefore, this study aimed to describe the demographic and clinical characteristics as well as treatment patterns (overall and stratified by maintenance regimen) among TE NDMM pts treated with DVRd as FL therapy in the real-world.

Methods: A retrospective, multi-center, chart review study was conducted at 9 clinical sites in the US. All eligible adults (except at one site, where eligible pts were randomly selected) with TE NDMM initiating FL DVRd therapy between January 1, 2019, and June 30, 2022, were included (index date = date of initiation). Pts were excluded if they previously received any treatment for MM for ≥30 days, previously participated in a clinical trial related to MM, were treated for any other invasive malignancy within 12 months prior to FL DVRd initiation or had amyloidosis at the index date. Demographic and clinical characteristics were evaluated up to 12 months pre-index and pts were followed until death or the last record of clinical activity. This abstract presents results from an interim analysis.

Results: A total of 180 pts initiating FL DVRd were included (median [interquartile range] age: 63 [12.5] years, age ≥65 years: 46.1%; male: 58.3%; White: 67.8%; Black: 11.7%), with a median follow-up of 26.4 months. Of 158 pts with a reported Eastern Cooperative Oncology Group (ECOG) score, 43.0% had a score of 0. Moreover, 86 pts had a reported R-ISS stage (I: 32.6%, II: 41.9%, III: 25.6%). Out of 151 pts with available data, 39 (25.8%) had high-risk cytogenetic abnormalities (HRC), including del[17p], t[14;16], or t[4;14]. Baseline demographics and disease characteristics are in line with the pts treated with DVRd in the PERSEUS (median age: 61.0 years; male: 59.4%; White: 93.0%; ECOG 0: 62.3%, HRC: 21.4%) and GRIFFIN (median age: 59.0 years; male: 55.8%; White: 82.0%; Black: 13% ECOG 0: 38.6%, HRC: 16%) trials. During follow-up, the median duration of the DVRd induction phase was 6.1 months and 128 (71.1%) pts received an autologous stem cell transplantation (SCT). Of the 51 pts without SCT, 37 (72.5%) deferred transplant, among which 21 (56.8%) of the deferrals went directly to maintenance therapy, with 14 (66.7%) using &gt;1 agent in maintenance. In the overall population, 17 (9.4%) pts received consolidation therapy and 155 (86.1%) pts received maintenance therapy, including 64 (41.2%) with R monotherapy, 60 (38.7%) with DR, 12 with VR, 7 with DV, 6 with DVR, 4 with V monotherapy, and 2 with D monotherapy.

The cohort treated with DVRd induction followed by DR maintenance (DVRd-DR) was slightly older (median: 65 years), had more males (63.3%), and a lower proportion of Black pts (6.7%) than the cohort with DVRd induction followed by R maintenance (DVRd-R; median age: 62 years, males: 56.3%, and Black: 14.1%). More pts in the DVRd-R cohort received a SCT (79.7% vs. 68.3%) than those in the DVRd-DR cohort. Compared to the DVRd-DR cohort, more pts with DVRd-R had ECOG score of ≥1 (63.9% vs. 45.0%). In contrast, the DVRd-DR cohort had more pts with HRC (17.0%) compared to DVRd-R (13.0%). For the DVRd-R and DVRd-DR group, the median duration of the induction phase was 6.4 and 6.1 months, respectively, and median duration of active maintenance was 16.5 and 14.3 months, respectively.

Conclusion: Compared to pts in the PERSEUS trial, the TE NDMM pts treated with FL DVRd identified in this real-world chart review study were observed to be older, and with a more diverse racial profile comparable to the US-only GRIFFIN trial population. In the real-world, use of consolidation therapy was less common and DVRd-DR maintenance was used more often in pts aged ≥65 years and in those with higher cytogenetic risk. Also, fewer pts with DVRd-DR than DVRd-R received a SCT. Data on outcomes will be presented at the conference, with additional pts expected.