Belantamab mafodotin plus lenalidomide/dexamethasone in newly diagnosed intermediate-fit & frail multiple myeloma patients: Long-term efficacy and safety from the phase 1/2 BELARD clinical trial.

7512 Background: We report the long-term safety & efficacy results of a novel, extended dosing schedule of belantamab mafodotin (belamaf) combined with Lenalidomide & Dexamethasone (Rd), in transplant-ineligible newly diagnosed Multiple Myeloma patients (pts). Methods: Phase 1/2 BelaRd trial (NCT04808037) Part 1 evaluated the safety/tolerability of belamaf 2.5/1.9/1.4 mg/kg plus Rd & established a recommended phase 2 dose (RP2D) of 1.9 mg/kg Q8W, extended to Q12W for Ocular Adverse Events (OAEs, Best Corrected Visual Acuity [BCVA] change from baseline & keratopathy). Dosing was led by ophthalmologist-assessed OAEs. In Part 2 RP2D is assessed in 2 groups: Dosing in Group A is guided as in Part 1 & in Group B by Vision-Related Anamnestic (a 9-question tool on pt-reported ocular symptoms & their impact on daily functioning) & ≥Gr3 OAEs. Safety/efficacy results from both Parts of the trial are presented. Results: Of Part 1 pts (n=36; median age: 72.5; male: 53%), 25 (69%) are ongoing & 11 (31%) discontinued (8 [22%] due to fatal events; 1 [3%] progressive disease; 2 [6%] withdrew consent). 17%/75% of pts had stage I/II disease per R-ISS & 8% high-risk cytogenetics (HRC). At a median follow-up (FU) of 36.2 months, Overall Response Rate (ORR) was 100%. Meaningful BCVA decline (Snellen <20/50 ) was recorded in 12% & Gr2/≥Gr3 keratopathy in 12%/3% of ocular exams. Median time to resolution was 1.9/1.1 months for ≥Gr2 BCVA/keratopathy OAEs, respectively. The most common (≥10%) Gr≥3 non-ocular AEs were fatigue, diarrhea, rash, COVID-19, pneumonia & insomnia. Of Part 2 pts (n=30; median age: 75; male: 67%), 22 (73%) are ongoing & 8 (27%) discontinued (6 [20%] due to fatal events; 1 [3%] progressive disease; 1 [3%] withdrew consent). 27%/63% of pts had stage I/II disease per R-ISS & 17% had HRC. At a median FU of 19.7 months, ORR was 96.7%. Meaningful BCVA decline was recorded in 27% & Gr2/≥Gr3 keratopathy in 9%/<1% of ocular exams. Median time to resolution of ≥Gr2 OAEs was 1.75 months. The most common Gr≥3 non-ocular AEs were fatigue & rash. The 12/24/36-months Time to Progression rates for all 66 pts were 98.2%/98.2%/94.4% (table 1). Conclusions: As has also been shown in the DREAMM-7/-8 studies,belamaf exhibits substantial clinical activity, with rapid, deep & durable responses in an unfit pt population, with only 2 PDs observed after a median of ~2 years FU. Only a few high-grade OAEs were recorded, that resolved quickly & no new safety signals were observed. Moving forward, the BelaRd combination, with the extended belamaf dosing schedule, warrants further investigation in larger pt numbers. Clinical trial information: NCT04808037 . Time to progression (TTP) rates in the overall population (66 pts). TTP rate in % (95% CI) 12 months 98.21 (87.99-99.75) 24 months 98.21 (87.99-99.75) 36 months 94.44 (77.81-98.70) CI: Confidence Interval.