Belantamab Mafodotin in Clinical Practice for Heavily Pretreated MM - Episode 5

Future Developments of Belantamab Mafodotin

March 29, 2021
Targeted Oncology

A leading authority in multiple myeloma comments on the future of belantamab mafodotin, such as combination therapy based on the DREAMM 5 and DREAMM 8 trials.

Sagar Lonial, MD, FACP: As with every drug in myeloma, if it works in refractory myeloma, then we want to bring it earlier and earlier in the treatment paradigm and start to partner it with some of our other commonly used agents in myeloma. What we know about belantamab mafodotin is that it has been partnered with bortezomib as part of the DREAMM 5 trial. We demonstrated that, in combination with bortezomib and dexamethasone, the incidence of keratopathy did not increase. In fact, the response rate was quite high, which suggested that these drugs can be combined. It opens the door to early relapse or even part of induction strategies, where bortezomib remains the mainstay as a proteasome inhibitor in the management of newly diagnosed myeloma.

Additionally, at ASH [American Society of Hematology Annual Meeting] last year, we saw interesting data from the Canadian myeloma group and Suzanne Trudel combining belantamab mafodotin with pomalidomide and dexamethasone. In this trial, they looked at alternative dosing schedules giving a lower dose once a week, giving a lower dose once every 3 weeks, or giving once every 4 weeks and partnering that with pomalidomide and dexamethasone. What was quite intriguing was that the response rate for that combination was quite high as well, and that the incidence of severe keratopathy was quite low. This may be quite interesting because, unlike other antibody-drug conjugates [ADCs], belantamab mafodotin retains the ability to fix complement. That functionally means that, by augmenting ADC, as you may get with pomalidomide, you may induce synergy by combining pomalidomide with belantamab mafodotin. We need a larger study to understand what this combination effect this, but if this works, then that would be an exciting combination to use belantamab mafodotin where you have an immune stimulant, such as pomalidomide partnered with an immune-based treatment.

Other combinations are coming. We are looking at belantamab mafodotin in other checkpoint inhibitor combinations, whether it is PD-1, LAG3, TIM3, or other synapse-associated antibody targets to see whether you can enhance the immunogenetic cell death that occurs with belantamab mafodotin by using immune-targeted agents. All these represent exciting steps going forward for belantamab mafodotin as part of the treatment paradigm in myeloma.

Transcript edited for clarity.