DREAMM-2: Single-Agent Belantamab Mafodotin (Belamaf) Effects on Patient-Reported Outcome (PRO) Measures in Patients with Relapsed/Refractory Multiple Myeloma (RRMM)

Introduction:
Belamaf (GSK2857916), a B-cell maturation antigen–targeting antibody-drug conjugate (ADC), demonstrated deep and durable responses with a manageable safety profile as a single agent in patients with heavily pretreated RRMM in the pivotal DREAMM-2 study (NCT03525678; Lonial ASCO 2020 Poster 436). Health-related quality of life (HRQoL) was evaluated via the cancer-specific European Organisation for Research and Treatment of Cancer quality of life questionnaire (EORTC-QLQ-C30; Popat EHA 2020 Poster EP1746), a PRO used extensively in oncology/MM studies to evaluate symptoms, functioning, and QoL. The EORTC-QLQ-MY20 module was used to assess MM symptoms. Corneal events are expected during belamaf treatment, as with other monomethyl auristatin F–containing ADCs, so two ophthalmic vision–related PRO questionnaires (National Eye Institute Visual Function Questionnaire-25 item [NEI-VFQ-25] and Ocular Surface Disease Index [OSDI]) were used to characterize the impact of corneal events on patient symptoms and visual function. Meaningful within-patient changes in OSDI and NEI-VFQ-25 scores were estimated to better interpret outcomes in this population (Eliason ISPOR 2020). We report here the results of the PRO analyses in DREAMM-2 according to measures used in the trial.

Methods:
In DREAMM-2, patients who received single-agent belamaf (2.5 or 3.4 mg/kg, every 3 weeks [Q3W]) completed PRO questionnaires electronically at baseline and Q3W during treatment. Group-level, mean change from baseline over time was evaluated on EORTC domains. We also evaluated the percentage of patients with ≥10-point meaningful change threshold for improvement (Osoba J Clin Oncol 1998) on EORTC domains over time. Meaningful change thresholds in ocular PROs measuring treatment-related corneal events were estimated using recommended anchor and distribution-based methods, with 12.5–16.6 points estimated as meaningful in this population, depending on the domain (Eliason ISPOR EU 2020). We report results of the PRO data analysis for patients in the 2.5-mg/kg group selected for clinical development.

Results:
At Weeks 7 and 13, 46% (21/46) and 41% (12/29) of patients who completed PROs improved ≥10 points in the EORTC-QLQ-C30 Fatigue domain score, respectively; 30% (14/46) and 31% (9/29) improved their General Pain domain score. For EORTC-QLQ-C30, there were trends toward improvement in Fatigue at some time points on treatment; Global Health Status (GHS)/QoL, Role Functioning, and Physical Functioning domain scores remained relatively stable. The EORTC-QLQ-MY20 Disease Symptoms domain score (representing pain in different locations) showed a general trend toward improvement over time, with improvements of ≥10 points at Weeks 7 and 13 for 38% (17/45) and 29% (8/28) of participants.

Ocular PRO data were available for 95% (92/97) of patients. Based on the OSDI vision-related functioning domain, a total of 49.5% of patients experienced a ≥12.5-point worsening from baseline (median time to worsening: 44 days). Meaningful improvement of these changes (based on defined 12.5-point thresholds) from worst severity post baseline was seen in 72% of patients (median time to improvement: 24 days). Importantly, even among patients with meaningful worsening in visual functioning, patient-reported QoL/GHS, Physical Functioning, and Role Functioning domains of the EORTC-QLQ-C30 remained stable while on treatment (Figure).

Conclusions:
Disease symptoms, functioning, and QoL did not worsen over time in these heavily pretreated patients receiving belamaf in DREAMM-2. Patients showed a general improvement in fatigue, which is often a difficult-to-manage symptom for patients with RRMM. Group-level, meaningful worsening in vision-related PRO domains was observed, which improved in the majority of patients. Despite ocular symptoms, even in patients with meaningful worsening, EORTC-QLQ-C30 data suggest that overall HRQoL and patient functioning remained stable while on treatment. These PRO results demonstrate a balance between overall QoL/functioning and vision-related impacts that, together with its clinical efficacy, supports the use of belamaf in the treatment of patients with RRMM.

Funding: GSK (study 205678); drug linker technology licensed from Seattle Genetics; mAb produced using POTELLIGENT Technology licensed from BioWa.