(OA-66) Maintenance Therapy with Belantamab, Pomalidomide and Dexamethasone in High-risk Myeloma Patients: A Phase 2 Study with a Safety Run-in - Interim Analysis
Professor, Director of Myeloma Program Winship Cancer Institute of Emory University Atlanta, Georgia
Introduction: Disease control among high-risk myeloma patients with combination maintenance strategies have resulted in improved outcomes. We have evaluated the safety and efficacy of BCMA ADC (belantamab) and IMiD (pomalidomide) in combination with dexamethasone in high-risk myeloma (NCT05208307).
Methods: Newly diagnosed high-risk myeloma pts that have achieved ≥PR post-ASCT were included. High-risk myeloma was defined by the presence of t(4;14) in 31.6%, t(14;16) in 10.5%, del17p in 57.9% pts by FISH or CTG or presence of ≥20% circulating cells (pPCL) in 21.1%. Double-hit myeloma (as defined by presence of ≥2 high-risk cytogenetic abnormalities including gain of 1q was seen in 73.7% of pts. Each cycle is 28 days. Belantamab 1.9 mg/m2 intravenously (IV) was given every 56 days and pomalidomide 4 mg PO on days 1 to 21 and dexamethasone 40 mg PO weekly. After the safety run in the first 6 pts, one DLT occurred and the DSMC recommendation was to continue 1.9 mg/kg of Belantamab administered IV every other cycle. A protocol amendment was made to administer belantamab 1.9 mg/kg every 12 weeks in the MTD group, after the first 2 doses received 8 weeks apart (56 days). In such case the ophthalmological evaluations can happen prior to the belantamab dosing q 12 weeks.
Results: 12 additional pts were enrolled. Median age was 59 (32 - 75). 52.6% male and 36.8% black. Median time from diagnosis and from transplant to study entry was 8.0 (range, 3.9 -11.0) and 2.4 (range, 1.9 – 4.6) months, respectively. At study entry, ≥CR and ≥VGPR rates were 31.6% and 52.6%, respectively, which deepened to 68.4% and 15.8% while on study. The median time to best response was 1 months (range, 0.43-13.8). Of the 14 pts with available MRD data, MRD (10-5) and (10-6) were achieved in 78.6% and 64.3%, respectively. After a median follow up of 6 months from study entry, and 15 months from diagnosis, none of the 17 evaluable patients for efficacy had progressed or died. In the MTD group, when patients receive belantamab 1.9 mg/kg every 12 weeks, there were no grade 3 or 4 events occurred. At data cut-off, all 17 pts were still receiving treatment. Most common (≥20%) TEAEs in the safety run in cohort (N=6) were blurry vision (83.3% [G3/4, 16.67%], pneumonitis/hypoxia ([G3/4, 33.3%]), dizziness (33.3%), diarrhea (33.3%), cough (33.3%) and peripheral neuropathy (33.3%) and a thromboembolic event occurred (G3/4, 16.66%). In the MTD group evaluable for safety (N=12) blurry vision (58.33%) and insomnia (33.33%) were the most common TEAEs. No grade 3 or 4 events occurred.
Conclusions: In pts with high-risk myeloma, BPd maintenance deepened responses, with MRD negativity (10-5) attained in 80% of pts. The extended dosing schedule of belantamab 1.9 mg/kg every 12 weeks is not associated with higher grade toxicities and had proven efficacy in this setting.The current results support the exploration of BPd maintenance in future high-risk studies. The current study will expand to include the new IMS-IMWG high-risk definition.
.jpg "Ajay K. Nooka, MD, MPH, FACP (he/him/his) photo")