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Updated data from the phase 3 DREAMM-7 trial was presented during the 2024 ASH Annual Meeting and Exposition.
Blenrep in combination with Velcade and dexamethasone improved survival and response rates compared to Darzalex in patients with relapsed or refractory multiple myeloma.
Patients with relapsed/refractory multiple myeloma experienced significant improvements in overall survival (OS) when treated with Blenrep (belantamab mafodotin) in combination with Velcade (bortezomib) and dexamethasone (BVd) versus those treated with Darzalex (daratumumab) plus Velcade and dexamethasone (DVd), trial results have shown.
Updated data from the phase 3 DREAMM-7 trial was presented during the 2024 ASH Annual Meeting and Exposition.
At a median follow-up of 39.4 months, the median OS was not reached (NR) in both the BVd (243 patients) and DVd (251 patients) arms. The predicted median OS based on modeling is 84 months with BVd versus 51 months with DVd. The estimated 24-month survival rates in the respective arms were 79% and 67%; these respective rates at 36 months are 74% and 60%.
Moreover, deeper responses were achieved and maintained with Blenrep vs Darzalex. The objective response rate (ORR) with BVd was 83.1% versus 71.3% with DVd. The median duration of response (DOR) with BVd was more than double that achieved with DVd, at 40.8 months and 17.8 months, respectively.
The percentage of those who achieved a complete response or better and minimal residual disease (MRD) negativity with a sensitivity of 10-5 was 25.1% in the BVd arm versus 10.4% in the DVd arm. The percentage of patients who experienced a very good partial response or better and MRD negativity with a sensitivity of 10-5 in the respective arms was 38.7% and 17.9%, respectively.
Overall survival (OS): the time a patient lives, regardless of disease status.
Objective response rate (ORR): patients who respond partially or completely to treatment.
Duration of response (DOR): the length of time a patient responds to treatment.
Complete response (CR): the disappearance of cancer.
Minimal residual disease (MRD): small amounts of remaining cancer cells.
Progression-free survival (PFS): the time a patient lives without their disease spreading or worsening.
Treatment benefit derived with BVd was also maintained after subsequent antimyeloma therapy. The median time to second objective disease progression (PFS2) with BVd was NR versus 33.4 months with DVd.
“BVd demonstrated an early, sustained and statistically significant OS benefit in a head-to-head trial against the [Darzalex] combination,” Dr. Vania Hungria of Clinica Sao Germano, in Sao Paulo, Brazil, said in a presentation of the data. “DREAMM-7 has now shown statistically significant [progression-free survival (PFS)], OS, DOR and MRD negativity benefits compared with DVd. [As such,] these results further support the use of BVd as a potential new standard of care in relapsed or refractory multiple myeloma.”
The randomized, open-label, phase 3 DREAMM-7 study enrolled patients with multiple myeloma who were at least 18 years of age and received at least one prior line of therapy and experienced documented progressive disease (PD) after their most recent line. Patients could not have previous exposure to anti-BCMA therapy, nor could they have disease that was refractory to or intolerant of Darzalex or Velcade.
Participants were randomly evenly assigned to receive Blenrep at a dose of 2.5 milligrams per kilogram (mg/kg) intravenously (IV) every three weeks paired with Velcade and dexamethasone versus Darzalex at a dose of 16 mg/kg IV weekly for cycles 1 to 3 and then every three weeks for cycles 4 to 8. For cycles 9 and later, those in the investigative and control arms received single-agent Blenrep at 2.5 mg/kg IV every three weeks or Darzalex monotherapy at 16 mg/kg IV every four weeks, respectively. Treatment continued until the study concluded, consent was withdrawn, PD, death or intolerable toxicity.
PFS served as the trial’s primary end point, and at a median follow-up of 28.2 months this was met. The median PFS of 36.6 months with BVd versus 13.4 months with DVd translated to a 59% reduction in the risk of disease progression or death. At the time of the primary analysis, median OS was NR in both arms, but a strong trend favored the BVd regimen. In November 2024, the FDA accepted a biologics license application seeking the approval of BVd in patients with multiple myeloma who have received at least 1 prior therapy based on DREAMM-7 data. The target action date is July 23, 2025.
Key secondary end points of the trial included OS, DOR and MRD. End points were tested in the following hierarchy: PFS, followed by OS and DOR, followed by MRD. Additional secondary end points of interest included CR rate, ORR, clinical benefit rate, time to response, time to progression, PFS2 and adverse effects (side effects), particularly ocular findings.
Of the total 494 patients enrolled, 243 were assigned to the BVd arm and 251 were assigned to the DVd arm; 242 and 246 patients, respectively, received treatment. A higher percentage of patients on the BVd arm remained on therapy versus those on the DVd arm, at 25% and 15%, respectively. The most common reason for discontinuation in the BVd arm was PD (30%), followed by toxicity (21%), physician decision (13%), patient withdrawal (10%), loss to follow-up (less than 1%) and protocol-defined stopping criteria reached (less than 1%).
The data cutoff date of the analysis shared during the meeting was Oct. 7, 2024. At this time point, the median duration of exposure to BVd was 15.9 months versus 12.8 months in the DVd arm. Baseline characteristics and prior treatments received proved to be balanced across the arms, according to Hungria, who added that approximately half of patients received one prior line of therapy.
“More patients in the BVd group discontinued treatment early due to progression and went on to receive a subsequent antimyeloma therapy,” Hungria said. “The most common subsequent therapy in both arms include immunomodulatory drugs like [Revlimid (lenalidomide)] and [Pomalyst (pomalidomide)]. Of patients who received subsequent therapies, more than half received anti-CD38 monoclonal antibodies immediately after BVd, and [Kyprolis (carfilzomib)] was given often after DVd.”
Regarding safety, any-grade side effects (AEs) occurred in all patients in the BVd and DVd arms; these effects were related to study treatment for 100% and 95% of patients, respectively. Grade 3 (severe) or 4 (life-threatening) AEs occurred in 95% and 78% of patients, respectively, with 92% and 67% related to study treatment. In the BVd arm, AEs led to dose delays or reductions for 95% and 75% of patients, respectively; in the DVd arm, these rates were 76% and 59%. AEs resulted in permanent discontinuation of treatment for 32% of those given BVd and 19% of those who received DVd. Serious AEs related to any study treatment were experienced by 21% and 13% of patients and serious AEs proved to be fatal for 11% and 8% of patients.
“AEs were consistent with the known safety profile for the individual agents in each regimen,” Hungria noted. “Although the BVd arm had numerically higher overall rates of grade 3 or 4 and serious AEs, when adjusting for total treatment exposure, safety results were generally comparable between arms. There were more deaths due to myeloma in the DVd vs the BVd arm.”
She added that thrombocytopenia was more common in the BVd arm, even when adjusted for exposure. Overall, infection rates were similar between the arms and consistent with the primary analysis. In the BVd and DVd arms, exposure-adjusted rates of infections per 100 person-years were 43.75% and 48.71% for all-grade events, and 19.89% versus 14.29%, respectively, for grade 3 or higher events.
“About two-thirds of patients did not have a clinically meaningful drop in best-corrected visual acuity, [BCVA]” Hungria said. “Overall, the ocular safety profile is consistent with the primary analysis. Nearly all patients with worsening of vision to 20/50 had resolution to normal baseline or improvement of the first event. The 2% of patients with an ongoing event had insubstantial follow-up to assess for resolution.” In the BVd arm, blurred vision was the most frequent ocular event experienced; 68% experienced an any-grade event and 24% experienced a grade 3 or 4 event. Ten percent of patients discontinued due to an ocular event.
“The interval between doses increased with time due to dose modification, from initial three weeks up to 12 weeks,” Hungria noted. “Despite the extended dose intervals, the responses were maintained.” Twenty-three percent of patients experienced 20/50 or worse ocular events in the first three months and prevalence generally dropped thereafter. Notably, the rate of treatment discontinuation due to these events was low, she concluded.
Reference:
Belantamab mafodotin, bortezomib, and dexamethasone vs daratumumab, bortezomib, and dexamethasone in relapsed/refractory multiple myeloma: overall survival analysis and updated efficacy outcomes of the phase 3 DREAMM-7 trial” by Dr. Vania Hungria et al., Blood.
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