P-122: Ocular Adverse Events and Functional Impact in Transplant Ineligible, Newly Diagnosed Multiple Myeloma Patients Treated with Belantamab Mafodotin, Lenalidomide and Dexamethasone in BelaRd Trial

Introduction: Ocular adverse events (OAEs), manifesting as visual acuity changes, ocular symptoms, and corneal findings, are common with belantamab mafodotin (belamaf; GSK2857916) and the main reason for dose modifications. Here, we present the OAEs and the associated functional impairment in transplant-ineligible (TI), newly diagnosed multiple myeloma (NDMM) patients (pts) treated with an extended dose schedule of belamaf in the phase 1/2 BelaRd study.

Methods: BelaRd (NCT04808037) is an open-label, phase 1/2 study conducted in Greece, aiming to enroll 66 TI NDMM pts. In Part 1, which investigates the safety/clinical activity of belamaf plus Rd, 36 pts are randomized (1:1:1) to receive belamaf at doses of 2.5, 1.9 or 1.4 mg/kg. In this part, belamaf is initially administered q8w and, depending on toxicity, dosing may be rescheduled to q12w. Ocular exams include Snellen best corrected visual acuity (BCVA) and slit lamp corneal evaluation. Ocular symptoms are classified by CTCAE v5.0, while the Ocular Surface Disease Index (OSDI) captures dry eye disease and activities of daily living (ADL). This descriptive analysis included all Part 1 pts (cut-off date 15/04/23).

Results: Among 201/227/192 BCVA assessments in cohorts 2.5/1.9/1.4, a worse than 20/50 result (in the better seeing eye) was observed in 21 (10%)/23 (10%)/18 (9%), while BCVA ≤ 20/200 was noted in 2 (1%)/3 (1%)/11 (6%), with a median time to resolution of 1 month. Across all cohorts, the most frequently reported ocular symptom ≥Gr 2 was dry eye (174/618, 28%), while ≥Gr3 keratopathy was noted in < 2% of assessments. Regarding OSDI, from 186/217/181 responses received, the number of "all/most' of the time worst responses in the ocular symptoms category were 5 (3%)/6 (3%)/8 (4%), while the respective proportions in the ADL category were 6 (3%)/4 (2%)/3 (2%). In terms of missed doses, among 122/129/112 planned belamaf infusions across cohorts, the number of skipped doses due to OAEs were 48 (39%)/41 (32%)/30 (27%). The overall response rate was 100%, no disease progression was observed over a median follow-up of 18.7 months, and 29 (81%) patients achieved at least VGPR while 15 (42%) achieved at least CR, with a median time to first response of 1 month.

Conclusions: Belamaf-Rd, with the extended schedule for belamaf, had a minimal impact in vision-related functioning, as the ‘all/most’ of the time worst answers in the ADL category of OSDI was < 3% across cohorts. Furthermore, the frequency of clinically relevant impairment in vision was low, as a meaningful BCVA decline was observed in ≤10% of assessments, with a rapid time to resolution. Finally, the treatment combination induced rapid, deep and durable responses across all dose levels. In conclusion, this novel extended belamaf schedule nearly eradicates the risk for clinically relevant ocular toxicity and impact on ADL, without any compromise in clinical activity.