Immune therapy with belantamab mafodotin and elotuzumab shows encouraging safety profile and preliminary efficacy in RRMM
Dr Natalia Neparidze - Yale School of Medicine, New Haven, USA
The Yale Myeloma Group is presenting the results of the phase Ib/II study of combination immunotherapy with elotuzumab, a SLAMF7 checkpoint inhibitor, and antibody-drug conjugate belantamab mafodotin for patients with late relapsed/refractory myeloma.
This patient population represents an unmet need. Patients in this study were heavily pretreated relapsed/refractory myeloma patients; they were all triple-class refractory and 80% of them were penta drug exposed. 40% of them had received prior BCMA-targeted therapy. The study followed a BOIN design with a starting dose of belantamab of 1.9mg/kg at every four weeks dosing and the study allowed dose reduction to 1.4 and interval to every eight weeks.
Currently we have completed the phase I portion of the study and the phase II expansion is ongoing so these results reflect the phase I portion of the study. The primary endpoint was safety and tolerability and it appears to be that the preliminary safety profile of this combination is favourable in that ocular toxicity, which is characteristic of belantamab mafodotin, appears to develop in 40% of this cohort which is not very high and all of them were grades 1-2 and resolved after discontinuation or withholding or dose modification of the drug. Other toxicities were pretty tolerable and this included haematologic toxicity like neutropenia, thrombocytopenia, anaemia. These were in the order of 20-30% so pretty reasonable. Infectious toxicity was also relatively reasonable, in the order of 30%, and these were pulmonary infections, only one of them was grade 3 so a pretty tolerable combination.
Of course this is early yet but with regards to the preliminary activity, 40% of patients achieved partial response in this heavily pretreated relapsed/refractory cohort. Another 30% of patients actually developed what appeared as stable disease, some of which were quite durable. It’s notable that two out of four patients who had prior failure and relapse after BCMA-targeted therapy achieved a partial response with this combination. So this is encouraging, so the combination appears to be safe and well tolerated overall and it may represent a good combination for heavily pretreated relapsed refractory myeloma, even after BCMA-targeted therapy failure.
What could be the impact of this research?
The combination represents yet another all immune combination which has a reasonable safety profile in comparison with some of the bispecifics or CAR Ts which require in-patient admission, are heavily immunosuppressive, require frequent growth factor administration etc., IVIG, high risk of infections, In comparison to that this combination is less toxic, all outpatient combination immunotherapy. It may represent a reasonable treatment combination for patients who are triple class refractory or penta drug exposed, those patients who have relapsed after prior BCMA targeted therapy you could consider this as a potential next line.
So we are continuing the study, the phase II portion is ongoing and, depending on the results, this may lead to a larger study, potentially with other combinations.
