The ongoing phase 1/2 DREAMM-6 trial demonstrated clinical activity and a good safety profile with the combination of belantamab mafodotin, bortezomib, and dexamethasone in patients with relapsed or refractory multiple myeloma.
The ongoing phase 1/2 DREAMM-6 trial (NCT03544821) demonstrated clinical activity and a good safety profile with the combination of belantamab mafodotin (Belamaf; Blenrep), bortezomib (Velcade), and dexamethasone in patients with relapsed or refractory multiple myeloma, according to preliminary data presented at the 2020 American Society of Hematology Annual Meeting.
“This combination demonstrated a high rate of overall response rates…very good partial response rates, and clinical benefit,” Rakesh Popat, MD, from University College London Hospitals, NHS Foundation Trust, said in his presentation. “The presented data support phase 3 studies for the potential adoption of this combination for…use in the treatment paradigm.”
For the 18 patients receiving 2.5 mg/kg of belamaf every 3 weeks with standard-of-care bortezomib and dexamethasone, there was an overall response rate (ORR) of 78% (95% CI, 52.4%-93.6%), with very good partial response in 9 patients (50%) and partial response in 5 patients (28%). Minimal response was observed in 1 patient and 3 patients (17%) had stable disease. There was also a clinical benefit rate of 83% (95% CI, 58.6%-96.4%). The median duration of response was not reached at a median of 18.2 weeks (range, 6.0-46.4) of treatment.
Of the patients with prior exposure to bortezomib, the ORR was 75%, and those with exposure to daratumumab (Darzalex) had an ORR of 67%; the clinical benefit rates were 81% and 67%, respectively.
Response rates increased for those treated in earlier lines of therapy. The ORR was 100% for patients treated in the second line compared with 50% for those who had received more than 3 prior lines of therapy.
All of the patients on the trial had treatment-related adverse events (AEs), although there were no new safety signals to date. Grade 3/4 AEs were seen in 16 patients (89%) and treatment-related serious AEs were seen in 5 (28%). No patients had any grade 5 AEs of interest. Serious AEs were reported in 67% and were considered related to treatment in 28%.
Dose reduction occurred in 13 patients (72%) and every patient has dose delays, 16 of which were for belamaf, to manage their AEs. There were 5 patients who had to discontinue treatment due to AEs from bortezomib (n = 4) and dexamethasone (n = 2), but none had to discontinue due to belamaf.
The AEs of interest included thrombocytopenia in 12 patients (67%), including of grade 4 in 8 patients and grade 3 in 3 patients; thrombocytopenia led to dose reduction in 6 patients (33%) and dose delay in 7 (39%). Grade 2 infusion-related reactions were observed in 3 patients (17%) but did not lead to dose modification or discontinuation.
Changes in the corneal epithelium occurred in all 18 patients, with grade 3 events in 10 patients, grade 2 in 7, and grade 1 in 1 patient. This AE led to dose reduction in 7 patients (39%), dose delay in 15 (83%), and no discontinuations. This was an anticipated AE associated with monomethyl auristatin F, the payload in belamaf, and was manageable with dose modifications and delays, according to Popat.
“In the pivotal phase 2 DREAMM-2 study, single-agent belamaf demonstrated deep and durable responses in patients with relapsed myeloma. The multimodal antitumor mode of action and an acceptable safety profile make belamaf a promising new therapy for use in relapsed/refractory myeloma combination regimens, with both proteasome inhibitors and immunomodulatory drugs,” Popat said.
The primary end point of the study were efficacy, safety, and tolerability. Patients received the combination for up to 8 cycles and maintenance with belamaf alone after. The median age of these patients was 67 years and 61% of patients were male. Thirty-three patients had high-risk cytogenetics and the median number of prior lines of therapy was 3 (range, 1-11).
The patients evaluated for this presentation were from the 2.5 mg/kg single-dose cohort in arm B and received bortezomib at 1.3 mg/m2 subcutaneously and dexamethasone at 20 mg intravenously or orally in combination with belamaf. Patients in arm A received lenalidomide (Revlimid) and dexamethasone in combination with the antibody-drug conjugate. Eligible patients had received at least 1 prior line of therapy, and prior exposure to bortezomib was allowed.
Popat R, Nooka A, Stockerl-Goldstein K, et al. DREAMM-6: Safety, Tolerability and Clinical Activity of Belantamab Mafodotin (Belamaf) in Combination with Bortezomib/Dexamethasone (BorDex) in Relapsed/Refractory Multiple Myeloma (RRMM). Paper presented at: 62nd American Society of Hematology Annual Meeting; December 5-8, 2020; Virtual. Abstract 1419. https://bit.ly/36NltpI