Daratumumab Versus Lenalidomide As Maintenance Therapy in Newly Diagnosed Multiple Myeloma - Interim Efficacy Results of a Randomized Clinical Trial

Introduction Maintenance strategies in newly diagnosed multiple myeloma (NDMM) are evolving given the availability of novel single agent and combination strategies aimed at improving progression free survival (PFS) without worsening quality of life. Current standard practice is indefinite lenalidomide (len) maintenance given its PFS and overall survival benefit (PMID: 28742454) however there are concerns about its long-term toxicities. Daratumumab (dara) as a single agent maintenance when compared to observation has been evaluated showing promising PFS rates (median PFS not reached v/s 45.8 months in CASSIOPEIA/PMID38889735; 18monthPFS 71.6% v/s 50.2% in ALCYONE/PMID29231133) and low non-progression discontinuation rates. Based on these ongoing trials of dara maintenance, this investigator-initiated randomized trial was designed to evaluate single agent dara versus the current standard len as a maintenance strategy. The early efficacy analysis of this ongoing trial is presented here. Methods This is an open-label single-center randomized study of maintenance therapy with dara compared to standard practice len (Shah et al. ASH abstract 2021; NCT04497961; n=100). Patients (pts) with NDMM who achieve a favorable response [very good partial response (VGPR) or better] after induction therapy with/without autologous stem cell transplant (ASCT) are eligible. Randomization is stratified by age and ASCT status (1:1) to receive maintenance therapy with either oral lenalidomide (10mg on days 1-21/28-day cycle [C]) (len arm) or daratumumab 1800mg subcutaneously (dara arm) per standard prescribing guidelines (weekly for C1-2; every 2 weeks for C3-6, every 4 weeks from C7-C37 unless disease progression/toxicity/withdrawal prior). Patients are followed with quality of life (QOL) surveys (every month) as well as serological (every 3 months) and annual PET and bone marrow biopsy assessments. The primary endpoint of this study evaluating QOL outcomes will be evaluated at the end of the study period. Herein, we report interim efficacy analysis of secondary endpoints with best response rates, MRD negativity rates and PFS. High risk cytogenetics were defined as presence of either t(4;14), t(14;16), t(14;20), del17p, gain/amp 1q or del1p. Response assessments were done per IMWG 2016 criteria and MRD negativity was assessed by flow cytometry (>10-5). The Kaplan-Meier approach was used to estimate PFS. Results At data cutoff in June 2024, 86 pts have been enrolled of whom 74 were evaluable (37 in len arm, 37 in dara arm) with a median follow up of 19.3 months. Of the 74 pts, median age was 70 with 44.6% ≥65yrs, 56.7% male; 70.3% White, 20.3% Black, 1.3% Asian and 8.1% other races. High risk cytogenetics were present in 32.4% in dara arm and 24.3% in len arm. In the len arm, 51.3% received quadruplets, 46% triplets and 1 pt received infusional chemotherapy. In the dara arm, 51.4% received quadruplets while 48.6% pts received triplet regimens. Dara during induction was received by 64.8% in dara arm and 56.7% in the len arm. ASCT was done in 81.1% of the len arm and 75.6% of the dara arm. Best responses to date in the len arm included 48.6% stringent complete response (sCR), 29.7% CR, 18.9% VGPR and 2.7% progression of disease and in the dara arm 70.2% sCR, 18.9% CR and 10.9% VGPR. Among those , MRD negativity was achieved at screening, year 1 and year 2 in len arm (43.2% [16/37], 48.1% [13/27], 64.3% [9/14]) and in dara arm (51.4% [19/37], 59.1% [13/22], 71.4% [10/14]) respectively. Pts on len arm demonstrated 12-month PFS of 89.7% (n=21) and 24-month PFS of 74.4% (n=9) while pts on dara arm 12-month PFS of 93.3% (n=24) and 24month PFS of 83.1% (n=10). Of 17 pts that came off the study prior to end of treatment, 11 were due to disease progression (6 in len arm; 5 in dara arm) and 6 due to other reasons [len arm - neuropathy (n=2), arthralgia (n=1); dara arm - pneumonitis (n=1), osteomyelitis (n=1) and new CML needing treatment (n=1)]. Conclusions The study enrolled a racially diverse population and early efficacy data suggest similar best response rates and 12- and 24-month PFS between dara and len arms. These data add to ongoing trials utilizing anti-CD38 monoclonal antibodies (mAbs) as part of maintenance strategies (NCT04071457; NCT03617731). Given encouraging efficacy signals, antiCD38mAbs may be considered an effective maintenance strategy, especially in pts with len intolerance. Updated data will be presented at the meeting.