Quality of Life in the Multicenter, Randomized, Phase 3 GMMG-HD6 Trial Applying Elotuzumab, Lenalidomide, Bortezomib and Dexaemethason in Patients with Newly-Diagnosed Multiple Myeloma

Background: The addition of elotuzumab to lenalidomide, bortezomib, and dexamethasone (RVd) therapy in transplant-eligible patients with newly diagnosed multiple myeloma (NDMM) did not demonstrate clinical benefit in terms of progression-free survival (PFS; Mai EK et al., 2024, Lancet Haematol.). Assessing the impact of treatment on quality of life (QoL) is crucial in understanding the holistic effects of new therapeutic regimens. Quality of life assessments have become increasingly important in MM management, reflecting a shift towards evaluating both survival outcomes and patient well-being (Fleischer A et al., 2023, J Cancer Res Clin Oncol.). Methods: QoL assessments were conducted among all 4 study arms in patients who received elotuzumab in addition to RVd induction and/or consolidation and lenalidomide maintenance, compared to those who did not receive elotuzumab (A1 vs. A2+B1+B2). The EORTC-QLQ-C30 and EORTC-QLQ-MY20 questionnaires were administered at baseline, during induction, consolidation, and maintenance phases. Scores were analyzed using weighted generalized estimation equations (WGEE) for longitudinal data with dependent observations. To control the family-wise type I error rate, a fixed-sequence testing procedure was used following FDA guidance. The hierarchical testing sequence for QLQ-C30 scores is specified in the following order: global health status (QL2), pain (PA), fatigue (FA), and emotional functioning (EF). Results: Data from 2346 QoL assessments across various treatment phases were included in the analysis. At baseline, 476 patients completed the EORTC-QLQ-C30 questionnaire. All evaluated patients showed reduction of PA and improvements in overall QoL across the treatment phases. Notably, there were no significant differences between the study arms in terms of QL2, PA, FA, and EF. Multivariable generalized linear regression analyses incorporating covariates treatment arm (A1 vs. A2+B1+B2) age, sex, WHO performance status, renal insufficiency, fractures, and response after induction therapy showed no significant impact of elotuzumab treatment vs. no elotuzumab treatment arms on QoL scores. Additionally, specific adverse events such as neuropathy, thromboembolic events, infections, and cardiac disorders were reported and analyzed. In terms of specific QoL scores, patients' QL2 improved significantly during induction, consolidation, and maintenance phases, with no significant difference between treatment groups. Significant reductions in PA scores were observed during all treatment phases, with consistent improvement across all groups. FA scores showed a significant decrease during all treatment phases, reflecting improved patient well-being over time. EF scores improved significantly across all treatment phases, indicating positive psychological impacts regardless of the treatment group. With respect to prognosis, QL2 at baseline revealed no significant effect on overall survival (OS) and progression-free survival (PFS) in multivariable Cox regression models. Conclusion: These results suggest that the addition of elotuzumab to RVd-based therapy, followed by lenalidomide maintenance, did not negatively impact the quality of life for transplant-eligible patients with NDMM. Despite variations in treatment regimens, patients reported consistent reductions in pain and improvements in overall QoL. Future studies should continue to focus on QoL and patient-reported outcomes, exploring the intricate relationship between QoL improvements and clinical outcomes in MM treatments.