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Belantamab Mafodotin Plus Pomalidomide and Dexamethasone in Relapsed/Refractory Multiple Myeloma: DREAMM 8
Dr. Fonseca: We were able to hear, at the last ASCO meeting, also a presentation by Dr. Suzanne Trudel from the Princess Margaret Hospital on the results of the randomized phase III study DREAMM 8 for patients with relapsed and refractory myeloma.
They report on the combination of belantamab mafodotin plus pomalidomide and dexamethasone versus pomalidomide plus bortezomib and dexamethasone. That’s the PBD regimen that was used in the OPTIMISMM clinical trial. And what they’re able to show is that the combination with belantamab significantly reduced the risk of progression or death, versus the PBD regimen, in patients who had received one or more prior lines of therapy. There was a suggestion, although it’s not proven yet, that there will be a translation into improvement in overall survival. There were better responses, and, of course, a benefit even in PFS.
Safety remains a concern
The safety issue remains, as has been reported, with the ocular events being the main toxicity. Although again, with further understanding of the dosing and interval of administration, I think we’re getting our arms around this toxicity better. So, now we have this as a new option, potentially as one of the standards of care in this patient population.
Dosing
The clinical trial was a one-to-one randomization. Again, these were patients who had one or more prior lines of therapy who were experiencing relapse. The belantamab dosing was at 2.5 mg per kg in cycle one, and then they administered 1.9 mg per kg intravenously every 4 weeks from cycle two onward. Pomalidomide and dexamethasone were administered as standard doses. And, for the bortezomib arm, they used the 1.3-mg dose on days 1, 4, 8, and 11 of cycles one through eight, and then it’s spaced out to every 2 weeks.
Progression-free survival as the primary endpoint
The primary endpoint for this clinical trial was progression-free survival. There were 302 patients allocated on the study, 155 to the belantamab arm and 147 to the PBD arm.
The patient population was well-distributed, so there were no obvious imbalances. And I would say that it’s important to note that all patients had prior exposure to lenalidomide. About a quarter of patients had prior exposure to daratumumab.
The primary endpoint, again, being progression-free survival, it has not been reached in the belantamab arm, whereas it was 12.7 months with the PBD regimen, which is consistent with what we know from the literature. At 12 months, the PFS was 71% for the belantamab arm, and, of course, the data are immature. But I wouldn’t be surprised if this exceeds 2 and gets close to 3 years once everything is said and done.
The subgroup analysis does not reveal any particular signal. The benefit is across the board, but we also see improved response rates for patients in the experimental arm. The overall response rate was 77% versus 72% for the control arm. Importantly, the rate of CR or better was 40% in the experimental arm versus 16% in the control arm.
Minimal residual disease negativity
Now, more and more we focus on the status of MRD negativity, and the MRD negativity that is reported with this particular regimen is higher. So, it was 32%, which is quite remarkable for this patient population versus 5% for the control arm. Of course, this translates into a longer duration of response, which is, by the way, an interesting aspect of belantamab, that sometimes the responses can be quite durable, even after one has to discontinue therapy, which is something we learned at the time where more frequent ocular toxicity would lead us to discontinue therapy.
So, once more, just like with the study presented by Dr. Mateos, I’m excited for the options this brings for our patients. And our decision as to who should get what for those earlier relapses in myeloma is now a decision that has to include belantamab mafodotin.
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