Evaluation of a novel method to guide belantamab mafodotin dosing in multiple myeloma based on a patient-reported questionnaire.

Abstract

7530 Background: Ocular adverse events (OAEs, best corrected visual acuity [BCVA] change from baseline and keratopathy) are common with belantamab mafodotin (belamaf; GSK2857916) and often necessitate an ophthalmic exam to guide dosing. Herein, we evaluate a novel approach for belamaf dose modifications in transplant ineligible patients (pts) with newly diagnosed MM, treated with an extended schedule of belamaf with lenalidomide and dexamethasone (Rd) in the BelaRd study. Methods: BelaRd (NCT04808037) is an ongoing, phase 1/2 study of 2 Parts. Part 1 established the recommended phase 2 dose (RP2D) of 1.9 mg/kg q8w, extended to q12w to account for OAEs. Part 2 assesses the safety/efficacy of RP2D in Groups A and B, of 15 pts each, and evaluates two sets of guidelines for OAE management. In Group A, dosing is determined by an ophthalmic exam performed by a certified ophthalmologist; in Group B it is determined by the pts’ responses in the Vision Related Anamnestic (VRA) tool and the presence of ≥Grade (Gr) 3 OAEs. VRA is a patient-reported questionnaire capturing ocular symptoms and their impact on activities of daily living (ADL). Herein, we present the OAEs and preliminary efficacy results after 205 ophthalmic and VRA assessments for all Part 2 pts (cut-off date 05/10/2023). Results: By the cut-off date, the median belamaf administrations and number of cycles reached were 3.0/3.0 and 8.0/7.0 for Groups A and B, respectively. The respective rates of Gr2 and ≥Gr3 BCVA change from baseline were 34.6%/24.2% and 6.4%/0.0%, while a meaningful BCVA decline (Snellen score <20/50) and ≥3 lines drop in the better-seeing eye was recorded in 11.0%/7.2% ophthalmological assessments; no ≥Gr3 keratopathy was observed. Among 110/94 VRA assessments, ocular symptoms and ADL impairment, manifesting for ≥50% of the time in the last 24 hours prior to belamaf administration (substantial time), were noted in 6.4%/10.6% and 3.6%/7.4%. Of note, VRA captured a “substantial time” response in 86% of assessments with ≥Gr3 OAEs. Finally, for the response-evaluable pts, at a median follow-up of 7.7 months, ORR was 93.3%/85.7% in Groups A and B (PR/VGPR/CR: 26.7%/53.3%/13.3%; 21.4%/64.3%/0.0%) and the median time to first response was ~ 1 month. Conclusions: The VRA tool was safe and effective in informing belamaf dose modifications. Future analyses will determine if VRA may effectively eliminate the need for an ophthalmic exam prior to belamaf dosing. Clinical trial information: NCT04808037 . [Table: see text]