Elotuzumab Boosts KRd Regimen in Newly Diagnosed Multiple Myeloma, Study Finds

The addition of elotuzumab to carfilzomib, lenalidomide, and dexamethasone (KRd) as an induction/consolidation treatment showed a favorable trend regarding the 3-year progression-free survival (PFS) rate for patients with newly diagnosed multiple myeloma (NDMM), according to data presented at the EHA 2025 Congress.

This phase 3 study study was led by Prof. Stefan Knop, MD of the Nuremberg General Hospital and Paracelsus Medical School. Treatment in the study involved transplant-eligible (TE) NDMM patients up to 70 years of age receiving six cycles of either KRd or E-KRd, followed by four consolidation cycles and subsequent maintenance (R or ER). 579 patients were randomized between August 2018 and October 2021 at 52 different sites.

For induction over 28-day cycles, patients received carfilzomib 20 (mg/m² IV), lenalidomide (25 mg PO, D1-21) and dexamethasone (36/40 mg). Elotuzumab was given on days 1, 8, 15, and 22 of Cycles 1 and 2, and on days 1 and 15 of cycles 3-6 (10 mg/kg IV).

For maintenance, patients received 10 mg of lenalidomide cycle for R maint, or 20 mg/kg IV of elotuzumab plus 10mg of lenalidomide for ER maintenance until progression/toxicity was reached. After induction, patients underwent bone marrow minimal residual disease (MRD) analysis by next-generation flow.

The first co-primary endpoint of the study, the rate of patients who achieved a very good partial response (VGRP) or better and were also MRD-negative post induction, was met, showing the superiority of E-KRd over KRd. The second co-primary endpoint was the 3-year PFS rate since randomization.

After a median follow-up of 46.4 months for KRd and 47.4 months for E-KRd, the median PFS could not be estimated for either arm. The 3-year PFS rate was not significantly different between the groups: 72.2% for KRd versus 78.7% for E-KRd.

In the maintenance phase, the rate of treatment-related adverse events was 78.1% with R versus 80.9% with ER. Two patients who received R maintenance versus one who underwent ER maintenance died due to study drug-related adverse events. The median duration of maintenance was comparable between the arms, with 249/574 (43%) of patients still on treatment, being 27.8 months for R versus 28.5 months for ER.

While the addition of elotuzumab to KRd showed a clear trend in favor of the PFS rate, the statistical significance was less than anticipated due to the “better-than-estimated” PFS for the KRd arm alone. The toxicity profile associated with ER maintenance was similar to that of R maintenance. Overall, the study signals a benefits of using monoclonal in NDMM treatment, however further research is required.