P-123: Safety and Clinical Activity of Belantamab Mafodotin plus Lenalidomide and Dexamethasone in Transplant Ineligible Patients with Newly Diagnosed Multiple Myeloma: The Phase 1/2 BelaRd study

Introduction: The combination of lenalidomide and dexamethasone (Rd) is preferred in the treatment of transplant ineligible (TI) patients (pts) with newly diagnosed multiple myeloma (NDMM). Belantamab mafodotin (belamaf; GSK2857916) is an antibody-drug conjugate targeting BCMA, which has shown efficacy in pretreated MM pts. Preclinical data demonstrate synergy between belamaf and lenalidomide, while these drugs do not have overlapping toxicities. Thus, there is a strong rationale for investigating the belamaf-Rd combination in TI NDMM pts.

Methods: BelaRd (NCT04808037) is an open-label, phase 1/2 study conducted in Greece, aiming to enroll 66 TI NDMM pts. Here we report results from Part 1 which evaluates the safety/tolerability of three belamaf doses (2.5/1.9/1.4 mg/kg) plus Rd in 36 pts and establishes the recommended phase 2 dose (cut-off date 15/04/2023). In this part, belamaf is initially administered q8w and, depending on toxicity, dosing may be rescheduled to q12w.

Results: Of the 36 pts [median age: 72.5 years; male: 19 (53%)] in Part 1, 29 (81%) are still on treatment, while 7 (19%) have discontinued [6 pts due to belamaf-unrelated fatal events: (COVID-19 infection: 1/1/2; Pneumonia: 1/1/0, for cohorts 2.5/1.9/1.4 respectively); 1 pt withdrew consent]. The median belamaf administrations and number of cycles reached were 6/7/7 and 18.5/21.5/18.5, for the respective cohorts. The most common (≥10% of pts) non-ocular ≥ Gr3 treatment-emergent adverse events were fatigue (21 pts, 58%; [7 (58%)/7 (58%)/7 (58%)]), rash (6 pts, 17%; [2 (17%)/2 (17%)/2 (17%)]), diarrhoea (8 pts, 22%; 2 (17%)/3 (25%)/3 (25%)]), insomnia (4 pts, 11%; 0/4 (33%)/0]) and COVID-19 infection (5 pts, 14%; [2 (17%)/1 (8%)/2 (17%)]), while no ≥Gr3 thrombocytopenias and infusion-related reactions were reported. Regarding ≥Gr3 infections other than COVID, pneumonia was reported for 3 (8%) pts [1 (8%)/1 (8%)/1 (8%)]. Among 201/227/192 best corrected visual acuity (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%). The overall response rate was 100% across all cohorts. More specifically, CR or better was achieved in 6 (50%)/4 (33%)/5 (42%), VGPR in 3 (25%)/7 (58%)/4 (33%) and PR in 3 (25%)/1 (8%)/3 (25%) of the pts in cohorts 2.5/1.9/1.4, with a median time to first response of 1 month. Finally, over a median follow-up of 18.7 months no disease progression was observed.

Conclusions: Belamaf-Rd, with the extended schedule for belamaf, has shown a very manageable safety profile with minimal impact in vision-related functioning in an elderly, non-fit pt population. Meanwhile, a very promising clinical activity is observed with rapid, deep and durable responses across all dose levels. Consequently, after validation with bigger pt numbers, this novel combination may well be a very attractive frontline option for this vulnerable TI-NDMM population.