Principal investigator Sagar Lonial, MD, FACP, discusses the DREAMM-2 trial and relapsed/refractory multiple myeloma.
Sagar Lonial, MD, FACP: Belantamab mafodotin [belamaf], was approved based on the DREAMM-2 study [NCT03525678]. DREAMM-2 was a randomized, phase 2 trial of belantamab mafodotin in patients with a median of 6 to 7 prior lines of therapy. In the context of this trial, patients were randomized to receive either 3.4 mg/kg of belamaf—which was the dose that was arrived at in the phase 1 study—or 2.5 mg/kg of belamaf, a dose that was suggested by the FDA as a way to try to reduce the incidence of keratopathy, the known and most common adverse event associated with the immunotoxin MMAF, which is what the BCMA [B-cell maturation antigen] antibody is linked with in belantamab mafodotin. We saw an overall response rate of [approximately] 30% in both arms, slightly higher with the higher dose. PFS [progression-free survival] was around 3 months for both arms… What was striking about this trial was that the duration of response [DOR] in the lower dose was 11 months [but it was] much shorter in the higher dose of belamaf. [Although] many may be perplexed by this, the reality is that the higher dose of belamaf was more difficult to give and was associated with more adverse events and higher-grade keratopathy. The reason the lower dose was chosen was that it appeared to be a safe, effective dose that did not [affect] how long responding patients could stay on therapy. It had a 30% response rate, median PFS of [approximately] 3 months, and a DOR of 11 months for the 2.5 mg/kg dose. When one looks at the FDA-approval trials for carfilzomib, daratumumab, and pomalidomide, they all look relatively similar. In fact, the 11 months with BCMA looks somewhat better, given that this was a median of 6 to 7 prior lines of therapy, and patients had all been exposed to carfilzomib, pomalidomide, and daratumumab prior to study entry. Overall, the safety and efficacy data from DREAMM-2 look favorable and led to the FDA approval of belamaf in the patient population. Additionally, what we did—and what was looked at ASH [Alliance for Shared Health] this year, as well as ASCO [American Society of Clinical Oncology Annual Meeting]—was look at responses based on prior therapy, and patients who had fewer than 6 lines of therapy were compared with patients who had more than 6 lines of prior therapy. We demonstrated that the response rate was similar between the 2, suggesting that because BCMA is a novel target, the efficacy of belamaf was not [affected] significantly by a lot of heavily pretreated patients vs less heavily pretreated patients across the board; remember, almost all the patients in this trial were triple-class refractory.
Transcript edited for clarity.
A 72-Year-Old Man with Heavily Pretreated, R/R Multiple Myeloma