Introduction: Patients refractory to an immunomodulatory agent and a proteasome inhibitor, and relapsed/refractory to an anti-CD38 antibody, are a population with a high unmet need given the poor prognosis in this setting. Single-agent belamaf (GSK2857916), a B-cell maturation antigen-binding antibody-drug conjugate, has demonstrated deep and durable responses with a manageable safety profile in heavily pretreated patients with RRMM. We used qualitative interviews to understand the patient perspective on clinical benefits and tolerability of belamaf.
Methods: Patients enrolled in the DREAMM-2 study (NCT03525678) received single-agent belamaf 2.5 or 3.4 mg/kg once every 3 weeks until disease progression or unacceptable toxicity. All were invited to participate in interviews at Cycle 4 (C4) and end of treatment (EOT). If the patient discontinued treatment before C4, only one interview was conducted. Interview questions covered the patient symptom experience, treatment-related burden, and adverse events. Disease and treatment-related symptom severity and overall treatment satisfaction were rated 0-10 (0=not severe to 10=most severe/0=not at all satisfied to 10=extremely satisfied). Qualitative and quantitative analyses were conducted with interview results and select variables from the clinical trial dataset.
Results: A total of 104 patients (across both doses) participated in interviews before or at C4, with 56% (n=58) identified as responders to treatment (≥partial response by International Myeloma Working Group criteria). Among the 104, the most commonly reported disease symptoms were fatigue (reported by 68% of patients), neuropathy (43%), and bone pain (37%). Responders reported a decrease in severity of these symptoms from the start of the study to the time of interview, with ratings changing from 6.9 to 3.6 (bone pain), 4.6 to 3.4 (fatigue), and 4.5 to 3.7 (neuropathy). The severity ratings for nonresponders increased slightly for fatigue (4.4 to 4.5) and decreased for bone pain (4.9 to 4.4) and neuropathy (3.9 to 2.8). Fifty-nine (57%) patients interviewed at or before C4 reported visual impairments, including poor vision, blurred vision, and sensitivity to light, while 42 (40%) reported symptoms of eye irritation, including irritated eyes, dry eyes, itchy eyes, and the feeling of something in the eye. Twelve (12%) patients reported eye pain, including sore eyes and burning at or before C4. Responders interviewed before or at C4 reported a mean treatment satisfaction of 8.5, while nonresponders reported their satisfaction at 5.1.
A total of 26 patients were interviewed at EOT after C4, 22 (85%) of whom were responders to treatment. Patients interviewed at EOT reported decreased severity in their ocular symptoms between the time when the symptoms were at their worst and the 2-week period prior to their interview. Between worst symptoms and interview, participant severity ratings showed a decrease from 8.0 to 0.0 (for eye pain; n=4), 7.2 to 1.8 (for eye irritation; n=11), and 8.1 to 2.9 (for visual impairment; n=17).
All 26 patients interviewed at EOT indicated they expected the ocular side effects they experienced. Six patients considered stopping treatment due to their ocular symptoms, two of whom reported their doctor discontinued treatment for this reason. At EOT, these 26 patients reported high treatment satisfaction, with responders rating their satisfaction higher than nonresponders (8.1 and 6.7, respectively).
Conclusions: Trial-embedded interviews provide valuable insights into the patient experience with their disease, the course of treatment-related side effects, and their overall impact on patient satisfaction with treatment. Overall, responders to treatment with single-agent belamaf reported more improvement than nonresponders in key disease symptoms, including bone pain and fatigue. Many patients reported some type of ocular symptom, but these were shown to improve or resolve by EOT. Despite ocular symptoms, overall, patients reported high satisfaction while on treatment and a desire to remain on treatment, particularly in responders. These qualitative interviews, in addition to the efficacy data, support the use of belamaf in patients with RRMM.
Funding: GSK 205678; drug linker technology licensed from Seattle Genetics; mAb produced using POTELLIGENT Technology licensed from BioWa.
Eliason:GSK: Current Employment, Current equity holder in publicly-traded company. Correll:Evidera: Current Employment. Martin:Evidera: Current Employment. Cardellino:GSK: Current Employment, Current equity holder in publicly-traded company. Opalinska:GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Piontek:GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Gorsh:GSK: Current Employment, Current equity holder in publicly-traded company. Sapra:GSK: Current Employment, Current equity holder in publicly-traded company. Popat:AbbVie: Consultancy, Honoraria; Bristol Myers Squibb: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Takeda: Consultancy, Honoraria, Other: Travel support, Research Funding; GSK: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company).
Asterisk with author names denotes non-ASH members.