Real-world outcomes with elotuzumab, lenalidomide, and dexamethasone in patients progressing on lenalidomide maintenance therapy: A single-center retrospective analysis

Abstract

Abstract Background: Elotuzumab, a monoclonal antibody targeting SLAMF7, demonstrated improved response rates and overall survival (OS) in combination with lenalidomide and dexamethasone (EloRD) in the phase III ELOQUENT-2 trial for relapsed/refractory multiple myeloma (RRMM). However, most patients in the U.S. nowadays are being treated in frontline with a lenalidomide-based regimen including maintenance, especially after high dose chemotherapy and autologous stem cell transplantation. Since such patients were excluded from the clinical trial, real-world treatment patterns, efficacy, and durability in more heterogeneous patient populations—particularly those receiving EloRD in later lines remain less well-characterized. Understanding outcomes outside of clinical trials is essential to inform therapeutic sequencing, especially in patients with diverse prior exposure and cytogenetic risk. Methods: Following institutional review board approval, we conducted a single-institution retrospective study of adult patients with RRMM who received EloRD following disease progression on lenalidomide maintenance therapy between January 2016 and December 2023. Demographic, clinical, and treatment-related variables were extracted from the electronic medical record. Key clinical outcomes, including overall response rate (ORR), OS, and time to treatment change, were estimated using the Kaplan–Meier method. Risk stratification was performed according to the 2024 IMS-IMWG Consensus Genomic Staging. Results: A total of 39 patients received EloRD following disease progression on lenalidomide maintenance therapy; the median age was 62 years (range 35–77), and 22 (56%) were male. Most patients were White–NonHispanic (30/39, 77%). The most common first-line regimen was lenalidomide, bortezomib, and dexamethasone (RVD), received by 24 patients (62%). EloRD was most commonly used as second-line therapy (22/39, 56%), followed by third-line (14/39, 36%), fourth-line (2/39, 5%), and sixth-line (1/39, 3%). Based on IMS-IMWG risk criteria, 23 (59%) were standard risk, 7 (18%) high risk, and 9 (23%) had no available data. At last follow-up, 31 patients (79%) had discontinued EloRD—most commonly due to progressive disease (21/31, 67%)—while 8 (21%) remained on treatment. The median time to treatment change was 9.83 months. Median OS from EloRD initiation was 73.9 months, with no significant OS differences by age, cytogenetic risk, R-ISS stage, or race. Compared to ELOQUENT-2 (ORR 79%, median PFS 19.4 months, median OS 48.3 months), our cohort demonstrated a lower ORR but longer OS, likely due to more effective post-progression therapies that became available. Despite these differences, progression-driven discontinuation rates and treatment durability were consistent with ELOQUENT-2, supporting the continued role of EloRD in real-world RRMM. Conclusions: In this real-world, single-institution cohort of RRMM patients previously treated with lenalidomide maintenance, EloRD demonstrated modest response rates and a median duration of nearly 10 months. Despite a lower ORR compared to ELOQUENT-2, the observed median OS exceeding six years suggests potential long-term benefit of elotuzumab-based therapy in appropriately selected patients. Beyond response metrics, EloRD remains clinically relevant as a well-tolerated option without cardiac or neuropathic side effects that can provide disease stabilization as bridging or holding therapy in patients awaiting access to definitive or cellular treatments. The absence of OS differences by cytogenetic risk or clinical stage may reflect limited sample size. These findings underscore the clinical utility of EloRD in lenalidomide-exposed patients and support its continued integration into real-world RRMM treatment strategies.