P-283: How to effectively administer belantamab mafodotin: Knowledge gained from the phase 1/2 BelaRd study in newly diagnosed transplant-ineligible patients with multiple myeloma

Introduction: Ocular adverse events (OAEs; best corrected visual acuity [BCVA] change from baseline and keratopathy) are common with belantamab mafodotin (belamaf). We present insights on belamaf dosing from the BelaRd study evaluating belamaf plus lenalidomide/dexamethasone (Rd) in transplant-ineligible patients (pts) with newly diagnosed multiple myeloma.

Methods: The ongoing phase 1/2 BelaRd study comprises 2 Parts. Part 1 (36 pts) evaluates the safety/tolerability of belamaf 2.5/1.9/1.4 mg/kg plus Rd and established the recommended phase 2 dose of 1.9 mg/kg Q8W/Q12W. Ocular exams are performed by an ophthalmologist, OAEs are graded with the Keratopathy Visual Acuity scale and belamaf dosing is permitted when OAEs are Gr0-1. Dry eye disease and vision-related functioning are assessed with the Ocular Surface Disease Index (OSDI). We present safety/efficacy results over an extensive follow-up period from Part 1 (cut-off date 29/03/24).

Results: Most pts (32/36; 88.9%) were switched to the Q12W schedule due to OAEs. Following an infusion at Gr0/Gr1, Gr≥2 OAEs were observed in 29.7%/48.8% of the subsequent ocular exams, while the median between-dose interval was 10.4/13.0 weeks (wks). Dosing belamaf when Gr< 2 or Gr≥2 dry eye, blurred vision, or visual impairment was observed, resulted in subsequent Gr≥2 ocular symptoms in 33.5%/80.5% of assessments and a median dosing interval of 12.4/14.7 wks. Regarding keratopathy, the proportion of ocular exams with Gr≥2 findings without concurrent Gr≥2 BCVA change from baseline was only 2.5%. Most (31/36, 86%) pts had cataract at baseline. Of note, in exams with Gr1 keratopathy findings, a higher proportion of Gr≥2 BCVA decline was observed when Gr3-4 (81.6%) than Gr0-2 (46.7%) cataract was present. Among 875 OSDI exams across cohorts, 40-46% reported ocular symptoms for “all/most/half of the time”, while the respective proportion for daily functioning impairment was only 5-10%. Over a median follow-up of 28.4 months, ≥CR and ≥VGPR was attained by 55.6% and 88.9% of pts; median time to response was ~1 month and only 1/36 (2.8%) pt had disease progression.

Conclusions: Our analyses highlight the importance of dosing belamaf when all previous OAEs are resolved completely, to mitigate the risk of subsequent ocular toxicity. To reduce peak toxicities, manifesting even with the extended dosing interval, dose reduction should be considered. High-grade cataract should be treated early, as it is a common problem in these pts that confers an additional risk for visual acuity decline. Severe keratopathy is rare, with a limited role in guiding dosing, as a discordance between BCVA and keratopathy was seldom observed. Although ocular symptoms were often reported, only a minor impairment in eyesight-related functioning was observed. Finally, the triplet regimen demonstrated substantial clinical activity, with rapid and deep responses, despite the extension of belamaf dosing to Q8W/Q12W.