Abstract
Introduction: Health-related quality of life (HRQOL) can be significantly impaired in patients with RRMM due to disease symptoms and adverse events associated with multiple lines of therapy as a result of relapse. Efficacious therapies with a novel mechanism of action are needed for patients at first relapse that also preserve HRQOL. In DREAMM-8 (NCT04484623), BPd demonstrated significant efficacy benefit vs a standard-of-care triplet regimen, pomalidomide plus bortezomib and dexamethasone (PVd). Ocular events, including blurred vision, were more common with BPd; however, previous reports have shown only a numerical increase in patient-reported overall symptom bother with BPd, and ocular events did not impact overall HRQOL. We sought to further contextualize the impact of meaningful visual changes and treatment benefit associated with BPd on patient-reported outcomes (PROs).
Methods: DREAMM-8 is an ongoing open-label, randomized, phase 3 study evaluating BPd (n=155) vs PVd (n=147) in patients with disease progression after ≥1 line of therapy, including lenalidomide. PROs were secondary and exploratory endpoints. European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 and MY20 are tools that use various scales to assess HRQOL in patients with cancer. This post-hoc analysis (data cutoff, January 29, 2024) focused on the impact of clinically meaningful changes in best corrected visual acuity (BCVA) across global health status/QOL, role functioning (eg, work/daily activities, hobbies), and physical functioning (eg, self-care, walking) domains. Patients were subdivided into 2 groups: (1) those with normal baseline BCVA (20/25 or better in ≥1 eye) who experienced bilateral worsening of BCVA to 20/50 or worse at any point on study and (2) those who either had normal baseline BCVA and did not experience a bilateral worsening to 20/50 or worse or did not have normal baseline BCVA. Ocular assessments occurred every 4 weeks and within 5 days prior to dosing; EORTC-QLQ-C30 and -MY20 were collected every 4 weeks from cycle 1, day 1 on a fixed schedule throughout treatment, and less frequent thereafter. Time to sustained deterioration (post hoc), defined as a meaningful decrease (10 points) in scores for ≥2 consecutive assessments or death, was assessed in the intent-to-treat population and focused on the EORTC QLQ-C30 physical functioning domain and MY20 disease symptoms. No formal hypothesis testing was performed.
Results: In the approximately one-third of patients treated with BPd who had normal baseline BCVA and experienced a change in bilateral BCVA to 20/50 or worse, patient-reported global health status/QOL, role functioning, and physical functioning domains were stable over time and comparable to those in patients treated with PVd. In the other two-thirds of patients, a trend (not meeting the meaningful change threshold) toward improvement in global health status/QOL and role functioning domains was observed with BPd vs PVd. EORTC QLQ-C30 physical functioning domain score was similar between patient groups and comparable to that in patients treated with PVd.
Treatment with BPd was associated with a delay in deterioration of a patient's ability to conduct day-to-day activities such as walking or self-care. Median time to sustained deterioration in physical functioning was longer in patients treated with BPd than in patients treated with PVd (16.43 vs 6.51 months; hazard ratio [HR], 0.69; 95% CI, 0.51-0.95). Treatment with BPd was also associated with a trend toward prolonged time to worsening of disease-specific symptoms (19.35 vs 12.65 months; HR, 0.85; 95% CI, 0.61-1.19).
Conclusions: Ocular events with BPd, although common, did not have a negative impact on HRQOL. In patients with clinically meaningful changes in vision (bilateral BCVA to 20/50 or worse), HRQOL measures were maintained during treatment, likely due to the transient nature of ocular events and the use of dose reductions and extensions, which have been shown to improve tolerability while maintaining efficacy. Treatment benefit associated with BPd led to a prolonged time to deterioration in physical functioning. These data provide a more comprehensive picture of overall HRQOL and further support BPd as a potential new treatment approach for RRMM.
Drug-linker technology licensed from Seagen Inc; monoclonal antibody produced using POTELLIGENT Technology licensed from BioWa.
