“Preliminary data for the 18 patients who have received belantamab mafodotin 2.5 mg/kg single dosing with bortezomib/dexamethasone suggests that this combination has an acceptable safety profile with no new safety signals identified. Clinical response looks promising."
The addition of the antibody-drug conjugate belantamab mafodotin to the standard-of-care doublet of bortezomib (Velcade) and dexamethasone (B-Vd) induced a minimum response of stable disease in all patients treated in a cohort of the phase 1/2 DREAMM-6 trial.1
The rate of clinical benefit (minimal response or higher) with B-Vd was 83% (95% CI, 58.6%-96.4%), and the rate of objective response (partial response or higher) was 78% (95% CI, 52.4%-93.6%).
“Preliminary data for the 18 patients who have received belantamab mafodotin 2.5 mg/kg single dosing with bortezomib/dexamethasone suggests that this combination has an acceptable safety profile with no new safety signals identified,” said Ajay K. Nooka, MD, MPH, FACP, associate professor in the Department of Hematology and Medical Oncology, Emory University School of Medicine, in a prerecorded presentation of the early findings for the 2020 American Society of Clinical Oncology (ASCO) Virtual Scientific Program. “Clinical response looks promising,” he added.
Belantamab mafodotin is an immunoconjugate targeting B-cell maturation antigen (BCMA) that has shown clinical activity in pretreated patients with relapsed/refractory multiple myeloma as a single agent. The antibody-drug conjugate exerts tumoricidal effects on the myeloma cells through the antibody-dependent cellular cytotoxicity and phagocytosis, Nooka explained.
The FDA is currently reviewing a Biologics License Application (BLA) for belantamab mafodotin monotherapy for the treatment of patients with relapsed/refractory multiple myeloma whose prior therapies included an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody, and the agency granted the BLA a priority review.2
Findings from the phase 2 DREAMM-2 trial contributed to the BLA showing responses in patients treated at either of 2 dose levels. Among 97 patients treated at 2.5 mg/kg intravenously every 3 weeks, responses were seen in 32% (97.5% CI, 21.7%-43.6%), and 35% (97.5% CI, 24.8%-47.0%) of 99 patients responded to treatment with the 3.4-mg/kg dose. The median duration of response was 11.0 months with the 2.5-mg/kg dose and 6.2 months with the 3.4-mg/kg dose.3,4
After a median follow-up of 13 months, the median overall survival was 14.9 months in the 2.5-mg/kg cohort and 14.0 months in the 3.4-mg/kg cohort. An acceptable safety profile was also seen with either dose.
DREAMM-6 is an ongoing open-label, 2-part, 2-arm trial that is investigating the efficacy and safety of the addition of belantamab mafodotin to 2 separate standard-of-care doublet regimens for patients with relapsed/refractory multiple myeloma who have previously received at least 1 line of therapy (NCT03544281). In one arm, belantamab mafodotin is combined with lenalidomide (Revlimid) and dexamethasone (B-Rd), and in the other arm, the agent is combined with bortezomib and dexamethasone. Part 1 was a dose-escalation phase and the ongoing part 2 is a dose-expansion phase for each of the arms with either single (day 1) or split dosing (day 1 and 8) for belantamab mafodotin at 2.5 mg/kg or 3.4 mg/kg.
Primary end points for the trial include dose-limiting toxicities; adverse events; electrocardiogram parameters of potential clinical importance; abnormal hematology, clinical chemistry, and urinalysis parameters; and ORR by International Myeloma Working Group Uniform Response Criteria.
In the B-Vd arm, patients were eligible for inclusion if they had received prior treatment with at least 1 prior treatment, measurable disease, prior stem cell transplant or ineligibility, an ECOG performance score of 0 to 2, adequate organ system functions, and no exposure to a monoclonal antibody therapy within 30 days of starting on the trial. Patients who were refractory to bortezomib were excluded from inclusion in this arm.
To date, 59 patients have been treated in the B-Vd arm with no dose-limiting toxicities observed at either dose level.
The ASCO presentation focused on 18 of these patients who received the 2.5-mg/kg single dose of belantamab mafodotin administered on day 1 of every 3-week cycle in combination with bortezomib and dexamethasone. Treatment with the triplet continued for up to 8 cycles followed by belantamab mafodotin monotherapy.1
Of these patients, the median age was 67 years (range, 47-83) and 61% of the patients were male. Twenty-two percent of patients had stage I disease, 44% had stage II, 17% had stage III, and 3 patients had unknown status. Eighty-three percent had an ECOG performance status of 0 to 1 and the remainder had a score of 2 or higher.
The median number of prior lines of therapy was 3 (range, 1-11), with 22% having received at least 7 prior regimens. One-third of patients had high-risk cytogenetics.
By investigator assessment, best response was a very good partial response for half of patients. Additionally, 28% achieved a partial response, 6% achieved a minimal response, and the remaining 3 patients (17%) had stable disease. “This aligns with other triplet combinations with the bortezomib and dexamethasone backbone,” Nooka said.
The median duration of response was not reached at the time of data cutoff. “As these study data mature, we will learn whether the response deepens further over time, and how durable treatment response is, but this early snapshot of the responses is encouraging,” he added.
The safety profile for B-Vd was considered acceptable with events consistent with the profiles for the individual components. At least 1 adverse event (AE) was reported in all patients and grade 3/4 events were observed in 89%.
AEs led to permanent discontinuation of one of the study treatments in 28% of patients—3 of these patients discontinued bortezomib, 2 discontinued dexamethasone, and 1 discontinued both, but no patients discontinued belantamab mafodotin. Dose reductions were required in 72% of patients and all patients required a dose interruption or delay at some point due to keratopathy (83%) and/or thrombocytopenia (39%). Serious AEs related to study treatment were observed in 28% of patients, but none were fatal.
The most common AEs with the regimen were corneal events—including keratopathy/microcyst-like epithelial changes, blurred vision, and dry eyes—and thrombocytopenia.
AEs of special interest included keratopathy, with grade 2 events occurring in 39% of patients and grade 3 events in 56%; grade 3 thrombocytopenia was observed in 17% and grade 4 in 44%; infusion-related reactions of grade 2 were observed in 17%.
Dose delays or reductions were used to manage most of these AEs as no premedications were given prior to belantamab mafodotin administration per protocol, according to Nooka. Data at the time of the presentation, though, were not mature enough to report on the resolution of corneal events. However, Nooka explained that in the DREAMM-2 trial, vision returned to baseline or near baseline levels for 81% of affected patients and no permanent loss of vision was reported.3
Nooka noted that findings from the rest of the study will be presented at future meetings when the data are more mature.