Daratumumab superior to active monitoring for high-risk smoldering multiple myeloma
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Key takeaways:
- Daratumumab delayed progression of smoldering multiple myeloma compared with active monitoring.
- Among those who began first-line myeloma treatment, patients who had been assigned daratumumab fared better.
SAN DIEGO — Daratumumab monotherapy significantly delayed progression of high-risk smoldering multiple myeloma to active multiple myeloma compared with active monitoring, according to results of the randomized phase 3 AQUILA study.
Daratumumab (Darzalex, Janssen) reduced risk for progression or death by 51%, findings presented at ASH Annual Meeting and Exposition showed. Less than 6% of patients had to stop treatment due to toxicities.
“This study may be practice changing as far as patients with smoldering myeloma and high-risk features are concerned,” Meletios A. Dimopoulos, MD, professor and chairman of the department of clinical therapeutics at National and Kapodistrian University of Athens School of Medicine in Greece, told Healio. “The importance of the study is reenforced further with the improved survival data that we also observed.”
Background and methods
Smoldering multiple myeloma is a precursor condition that can progress to multiple myeloma. However, patients often do not show symptoms and there are no treatment options, according to study background.
“Among patients with smoldering myeloma, there is a subset of patients with features that may predict a more rapid progression to symptomatic myeloma,” Dimopoulos said. “These are considered as ‘high-risk smoldering myeloma’ and have a 50% probability to progress to symptomatic myeloma within 2 years from diagnosis. For these patients, it is important to establish treatments that may delay progression to symptomatic disease and avoid end-organ damage, such as severe anemia, bone lesions and renal impairment.”
The FDA approved daratumumab as monotherapy for relapsed or refractory multiple myeloma, and as part of combination therapies for those with newly-diagnosed or relapsed/refractory disease.
The AQUILA study included 390 adults (median age, 64 years; range, 31-86; median time from diagnosis to randomization, 0.72 years; range, 0-5 years) with high-risk smoldering multiple myeloma.
Researchers randomly assigned 194 study participants to daratumumab, with treatment administered in 28-day cycles. Participants received daratumumab once weekly for the first two cycles, once every 2 weeks in the third through sixth cycles, and once every 4 weeks until they completed 39 cycles (36 months) or developed disease progression.
The other 196 study participants underwent active monitoring.
PFS served as the primary endpoint. Overall response rate, PFS on first-line multiple myeloma treatment and OS served as secondary endpoints.
Results and next steps
Median treatment duration in the daratumumab group reached 35 months, equivalent to 38 cycles.
Median follow-up was 65.2 months (range, 0-76.6).
Results showed significantly prolonged PFS in the daratumumab group (median, not reached vs. 41.5 months; HR = 0.49; 95% CI, 0.36-0.67).
Other outcomes favored daratumumab, including estimated 60-month PFS rate (63.1% vs. 40.8%), ORR (63.4% vs. 2%; P < .0001), and percentage of patients who had to start first-line multiple myeloma treatment (33% vs. 52%).
Median time from randomization to first-line multiple myeloma treatment had not been reached in the daratumumab group vs. 50.2 months for the active monitoring group (HR = 0.46; 95% CI, 0.33-0.62).
Among those who initiated first-line multiple myeloma treatment, those who had been assigned daratumumab achieved longer PFS (HR = 0.58; 95% CI, 0.35-0.96) and had higher likelihood of achieving 60-month OS (93% vs. 86.9%; HR = 0.52; 95% CI, 0.27-0.98).
“We saw a benefit across all subsets, but the greatest benefit was for the high-risk patients,” Dimopoulos said during a press briefing.
Fifteen patients assigned daratumumab died compared with 26 assigned active monitoring.
A higher percentage of those assigned daratumumab developed grade 3 or grade 4 treatment-emergent adverse events (40.4% vs. 30.1%), the most common being hypertension (5.7% vs. 4.6%).
Results showed 5.7% of participants discontinued daratumumab due to treatment-emergent adverse events. A comparable percentage of those assigned daratumumab vs. active monitoring developed treatment-related adverse events that led to death (1% vs. 2%).
“Now that we have established that daratumumab is effective in patients with high-risk smoldering myeloma, we need to develop combinations with this compound and with other agents in order to improve further these positive results,” Dimopoulos told Healio.
For more information:
Meletios A. Dimopoulos, MD, can be reached at mdimop@med.uoa.gr.
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Dimopoulos MA, et al. Abstract 773. Presented at: ASH Annual Meeting and Exposition; Dec. 7-10, 2024; San Diego.
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