Abstract
Belamaf, a BCMA targeting antibody-drug conjugate (ADC), combined with standard therapies, demonstrated statistically significant and clinically meaningful progression-free survival (PFS) and overall survival benefit in DREAMM-7 (NCT04246047) and PFS benefit in DREAMM-8 (NCT04484623) in patients with relapsed/refractory multiple myeloma (RRMM) with ≥1 prior line of treatment. Ocular events are frequently observed with various ADCs including with belamaf combinations. In DREAMM-7 and DREAMM-8, ocular events were managed and reversed with protocol-mandated dose modifications guided by corneal exam findings and visual acuity assessments, which are common exams that can be implemented by eye care professionals (optometrists or ophthalmologists) in clinical practice. We sought to better understand how these standard exams can help to guide dose modifications and manage belamaf-related ocular events.
Patients were randomized 1:1 to belamaf, bortezomib, and dexamethasone (BVd) vs daratumumab-Vd (DVd) in DREAMM-7 or belamaf, pomalidomide, and dexamethasone (BPd) vs PVd in DREAMM-8. Ocular exam findings (OEFs) comprised 2 components: (1) corneal exam findings by slit lamp exam and (2) changes in best-corrected visual acuity (BCVA) measured by Snellen chart. OEFs were graded using the KVA scale and the overall grade determined by the more severe grade of the 2 components in the worse affected eye; a grade ≥2 drove protocol-recommended belamaf dose modifications (dose delays until resolution to grade 1 or baseline and/or dose reductions). For these post hoc analyses, the first 5 occurrences of grade ≥2 OEFs, as applicable, were reviewed, and BCVA changes were further evaluated in patients with normal baseline BCVA (ie, 20/25 or better in ≥1 eye). Specifically, bilateral BCVA changes to 20/50 or worse were evaluated to better understand the impact on the overall visual function.
DREAMM-7 included 494 patients (BVd, n=243; DVd, n=251).As of October 7, 2024, data cutoff (median follow-up, 39.4 months), 87% (779/899) of all grade ≥2 OEF occurrences had resolved. Of the remaining patients with grade ≥2 OEFs that had not resolved by the data cutoff, the majority were either still in follow-up (8%) or had died or withdrawn from the study (5%), which prevented complete capture of resolution data. Overall, 146 of 242 patients (60%) had multiple grade ≥2 occurrences. The median time to resolution to grade 1 or better of the first 5 occurrences was consistent and predictable, ranging from 12-17 weeks.
Incidence of bilateral BCVA change to 20/50 or worse in patients with normal baseline was 34% (82/242) at the October 2, 2023, data cutoff (primary analysis). These patients had worsening in vision for a median of 7% of their time on treatment. The first incident of bilateral BCVA 20/50 or worse resolved in 94% of patients; median time to improvement and resolution of this first event was 3 and 9 weeks, respectively. This was earlier than the resolution of OEFs, suggesting that meaningful vision changes resolved prior to corneal exam findings.
While impact on visual function is often assessed by considering changes in both eyes, belamaf dose modifications were more conservatively guided by OEFs (± symptoms) using the worse eye to guide dose adjustments. At the October 2, 2023, data cutoff, 63% (152/242) of patients with baseline BCVA 20/50 or better in ≥1 eye had ≥1 unilateral BCVA change to 20/50 or worse. Unilateral BCVA change to 20/50 or worse was improved in 94% of occurrences and resolved in 80% of occurrences, with a median time to improvement of 3 weeks and to resolution of 12 weeks.
Similar results were observed with BPd in DREAMM-8.
Belamaf-relatedocular events can be detected using routine eye-care professional assessments and can be managed and reversed with appropriate dose modifications and follow-up. These events are commonly self-limiting with dose delays due to the regenerative nature of the corneal epithelium. Dose modifications were driven by the more conservative unilateral vision changes; clinically meaningful bilateral vision changes were less frequent and transient with high resolution rates, supporting the dose modification approach in DREAMM-7/8.
Drug-linker technology licensed from Seagen Inc; monoclonal antibody produced using POTELLIGENT Technology licensed from BioWa.
