Belamaf Regimen Improves Progression-Free Survival in Myeloma

For patients with relapsed or refractory myeloma, Belamaf (belantamab mafodotin) plus bortezomib and dexamethasone — a regimen referred to as BVd — lengthened the time that patients lived before experiencing disease progression compared to those treated with Darzalex (daratumumab), bortezomib and dexamethasone (DVd), according to research presented at the 2024 American Society of Clinical Oncology Annual Meeting.

Data were simultaneously published in The New England Journal of Medicine.

The median progression-free survival (PFS; time patients live until disease worsening) with BVd was 36.6 months compared with 13.4 months for DVd, representing a 59% reduction in the risk of progression or death.

Data for overall survival (OS; time from treatment until death of any cause) were not ready at the time that the researchers collected data, meaning that not enough patients had died for them to calculate an average. At 18 months, 84% of patients remained alive in the BVd group compared with 73% in the DVd arm, indicating an early, but not yet statistically significant, reduction of 43% in the risk of death. When an outcome difference between two datapoints is not statistically significant, it means that the researchers could not be certain that one regimen performed better than the other.

“There was a statistically significant and clinically meaningful progression-free survival benefit, with a strong and clinically meaningful overall survival benefit favoring BVd over DVd. All the response as well as the different response categories were also in favor of BVd,” lead investigator Dr. María-Victoria Mateos, Hospital Universitario de Salamanca, Instituto de Investigación Biomédica de Salamanca (IBSAL), Centro de Investigación del Cáncer (IBMCC-USAL, CSIC), said during a presentation of the results. “These trials support the potential for BVd as a potential new standard of care for relapsed/refractory myeloma patients.”

In the study, 494 patients were randomly assigned to receive BVd (243 patients) or DVd (251 patients).

The median age of patients in the BVd arm was 65 years and was 64 years in the DVd arm. The ECOG performance score was 1 or less for 96% of patients, meaning that the patients could independently perform all of their daily tasks. Most had stage 1 or 2 disease (95%). The median time from diagnosis in the BVd arm was 4.3 years compared with 3.9 years in the control group. Two-thirds of patients had standard cytogenetic risk, meaning that they did not have genetic mutations associated with poor prognosis (72% and 70% in the BVd and DVd arms, respectively). The most common high-risk cytogenetic characteristics was t(4;14), which was present in 17% of participants. This was followed by a deletion in 17p13 for 12% in the BVd group and for 14% in the DVd arm.

Extramedullary disease (myeloma located outside of the bone marrow) was present for 5% of those in the BVd arm compared with 10% of those in the DVd group. Half of patients had received one prior line of therapy, and 12% in the BVd arm and 11% in the DVd group had received four or more lines of therapy. Prior therapies were similar between groups and the time to relapse after the most recent therapy was the same for each group, with 20% having relapsed in 12 or less months. There were 2% of patents in the DVd arm who had received prior Darzalex. Rates of prior chemotherapy and autologous stem cell transplantation were similar.

In a pre-specified subgroup analysis, Mateos noted that BVd was superior to DVd across all subgroups, including those with disease that did not respond to prior Revlimid (lenalidomide) and those with high-risk cytogenetics.

Deeper responses were noted with BVd versus DVd, Mateos noted. The objective response rate (ORR; percentage of patients whose disease shrunk or disappeared) with BVd was 82.7%, which consisted of a stringent complete response (sCR; when there are no myeloma cells or proteins detected in the bone marrow or urine) rate of 14% and a complete response (CR; no disease detected in the bone marrow) rate of 20.6%, for a CR or better rate of 34.6%.

The CR or better rate with DVd was 17.1% and consisted of a sCR rate of 5.2% and a CR rate of 12%. The ORR in the DVd arm was 71.3%. Minimal residual disease (MRD)-negative (no cancer detected in the blood) CRs were experienced by 24.7% of those in the BVd arm versus 9.6% in the DVd arm. Very good partial responses (VGPR; 90% or more decrease in blood M protein, associated with myeloma) were seen in 31.3% of those treated with BVd and for 29.1% of those treated with DVd. MRD-negative VGPR or better rates were 38.7% and 17.1% for BVd and DVd, respectively.

“The CR rate or better was doubled with BVd and it is important to note the superiority of MRD negativity rate, which in myeloma is one of the most important factors predicting outcome,” Mateos said.

Side effects of any grade was experienced by all patients enrolled in the trial. Moderate to severe (grade 3/4) side effects that were related to treatment occurred in 90% of those enrolled in the BVd arm compared with 67% in the DVd group. Side effects led to treatment discontinuation for 31% of patients in the BVd arm compared with 19% in the DVd group. Side effects led to a dose reduction for 75% of patients in the BVd group compared with 59% in the DVd group. Treatment-related serious side effects were seen in 19% of those in the BVd group and for 12% in the DVd group. Fatal side effects related to study drug were experienced by seven patients in the BVd arm compared with two in the DVd arm.

Changes in baseline correct visual acuity were the most unique side effects, Mateos noted. Overall, 34% of patients experienced a worsening in visual acuity from 20/20 to 20/50, or blurred vision, Mateos said. There were 2% of patients who experienced a shift to 20/200 vision, or impaired vision.

“With dose adjustments and delays, a majority of patients resolved these ocular events, and only 9% of patients had to discontinue treatment due to ocular events,” said Mateos.

An analysis was conducted to examine whether dose interruptions and delays impacted PFS. For those with one or more dose delays that lasted 12 weeks or longer, the median PFS was 36.6 months, which matched the overall median for the trial. Moreover, quality was not different between groups, Mateos noted.

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