The Impact of Patient-Reported Adverse Events on Quality of Life: An Analysis of the Dreamm-7 and Dreamm-8 Randomized Controlled Trials

Introduction: Belantamab mafodotin (belamaf) is being investigated in 2 separate phase 3 trials in patients with relapsed/refractory multiple myeloma (RRMM) who had received ≥1 prior therapy: DREAMM-7 (NCT04246047) is investigating belamaf in combination with bortezomib and dexamethasone vs daratumumab, bortezomib, and dexamethasone, and DREAMM-8 (NCT04484623) is investigating belamaf in combination with pomalidomide and dexamethasone vs bortezomib, pomalidomide, and dexamethasone in lenalidomide-exposed patients. In both trials, belamaf combination treatment demonstrated significant progression-free survival (primary endpoint) benefits over the comparator treatment (DREAMM-7: hazard ratio [HR], 0.41; 95% CI, 0.31-0.53; P<0.001 [Hungria N Engl J Med 2024]; DREAMM-8: HR, 0.52; 95% CI, 0.37-0.73; P<0.001 [Dimopoulos N Engl J Med 2024]). Additionally, in both trials, patient-reported outcome (PRO) analyses showed that patients' health-related quality of life (QOL) was stable over time and comparable between arms. Adverse events (AEs) can impact patients' QOL and reduce the tolerability of a treatment, which may interfere with treatment administration and negatively impact clinical outcomes. Blurred vision is a commonly reported ocular AE with belamaf that has been managed by dose modifications in DREAMM-7 and DREAMM-8, and its impact on patients is of particular interest. This analysis used data from both trials to evaluate the impact of AEs, including blurred vision, on patient-reported health, including functioning and QOL. Methods: The DREAMM-7 (N=494) and DREAMM-8 (N=302) studies collected PRO data at specified time points per protocol, including responses on the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire 30-item Core Module (EORTC QLQ-C30), EQ-5D visual analog scale (VAS), and Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). The EORTC QLQ-C30 measures patients' overall QOL, functioning, and symptoms. The EQ-5D VAS is a scale in which patients visually mark their overall health on a thermometer-style line. The PRO-CTCAE evaluates patients' experiences of symptomatic toxicities. For this study, the following items from the PRO-CTCAE were analyzed: decreased appetite, nausea, vomiting, mouth/throat sores, problems tasting food/drink, constipation, loose/watery stool, shortness of breath, cough, itchiness, numb/tingling hands and feet, blurred vision, watery eyes, abdomen pain, fatigue, pain/burning urination, shivering/shaking chills, and nosebleeds. Fourlinear regressions were performed separately for each trial (data from both treatment arms were pooled in each trial), with PRO-CTCAE composite grades as the explanatory variable in each analysis and one of the PRO measures as the response variable, namely: EORTC QLQ-C30 global health status (GHS)/QOL, EORTC QLQ-C30 role functioning (RF), EORTC QLQ-C30 physical functioning (PF), and EQ-5D VAS. Results: In DREAMM-7, among the AEs analyzed, fatigue had the greatest impact on self-assessed measures of health, including GHS/QOL (estimated parameter, −7.94), RF (−13.88), PF (−8.71), and EQ-5D VAS (−6.52) (P<0.01 for all analyses). Decreased appetite also significantly impacted GHS/QOL (−3.22), RF (−3.92), PF (−3.90), and EQ-5D VAS (−2.49) (P<0.01 for all analyses). In contrast, blurred vision had a relatively minor impact (GHS/QOL: −0.56, P<0.01; RF: −1.42, P<0.01; PF: 0.32, P=0.10; EQ-5D VAS: −0.02, P=0.93). In DREAMM-8, fatigue and decreased appetite also had the greatest impacts on all 4 measures (GHS/QOL: −7.40 and −4.44; RF: −10.68 and −7.07; PF: −10.84 and −5.52; EQ-5D VAS: −6.41 and −3.33, respectively; P<0.01 for all analyses). In contrast, blurred vision had relatively minor impacts (GHS/QOL: −0.35, P=0.25; RF: −0.66, P=0.11; PF: 1.34, P<0.01; EQ-5D VAS: −0.51, P=0.19). Analyses by arm were consistent with the pooled results. Conclusions: These data show that fatigue and decreased appetite were the AEs with the greatest impact on patient-reported health in DREAMM-7 and DREAMM-8, whereas blurred vision did not have a substantial negative impact. These data also underscore the importance of adequate management of all AEs. Overall, these results further support belamaf combinations as a potential new standard of care in patients with RRMM. Funding: GSK (study #220933)