According to results of a phase 2 study, monotherapy with daratumumab, a CD-38–directed monoclonal antibody, showed clinical activity and tolerable safety in patients with intermediate- or high-risk smoldering multiple myeloma. The findings from this study were published in Leukemia.1

Smoldering multiple myeloma is a premalignant, asymptomatic clonal plasma cell disorder that increases the risk of developing multiple myeloma. However, at the present time, active monitoring for development of multiple myeloma is considered to be the standard-of-care for patients with smoldering multiple myeloma.

Because multiple myeloma is currently considered to be incurable, and most patients with intermediate- or high-risk smoldering multiple myeloma experience disease progression to multiple myeloma, treatment approaches to delay or prevent progression of smoldering multiple myeloma are under active investigation.

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For example, results of a recently conducted phase 3 clinical trial comparing the combination of lenalidomide plus dexamethasone with active monitoring in patients with intermediate- or high-risk smoldering multiple myeloma showed a decreased likelihood of developing multiple myeloma and increased overall survival for those receiving treatment compared with surveillance alone.2 Nevertheless, the associated treatment-related toxicities of that approach, including 1 treatment-related death,  have prompted investigators to look for a less-toxic intervention in this setting.

In this open-label, multicenter study ( Identifier: NCT02316106), 123 adult patients with intermediate- or high-risk smoldering multiple myeloma were randomly assigned in 1:1:1 ratio to receive single-agent daratumumab (16 mg/kg, intravenously) in a dosing schedule involving 8-week cycles and classified as intense (cycle 1 [weekly]; cycles 2,3 [every 2 weeks]; cycles 4-7 [every 4 weeks]; cycles 8-20 [every 8 weeks]), intermediate (cycle 1 [weekly]; cycles 2-20 [every 8 weeks]), and short (cycle 1 [weekly]), respectively. The coprimary endpoints of the study were complete response (CR) rate and the rate of disease progression or death per patient-year.

Baseline patient characteristics included a median age of 61 years, and short time (5.5 to 7.4 months) from diagnosis of smoldering multiple myeloma to study enrollment. More than 80% of patients had an Eastern Cooperative Oncology Group (ECOG) performance status of 0.

At a median follow-up of 25.9 months, the CR or better rate was 4.9%, 9.8%, and 0% for patients in the intense, intermediate, and short daratumumab dosing arms, respectively. Overall response rates (ORR) were 56.1% [intense dosing], 53.7% [intermediate dosing], and 37.5% [short dosing], respectively. In addition, rates of very good partial response were 24.4%, 14.6%, and 17.5%, respectively, and partial response rates were 26.8%, 29.3%, and 20.0%, respectively, for patients assigned to these respective study arms.

Rates of disease progression or death per patient year were 0.059, 0.107, and 0.150 for patients receiving intense, intermediate, or short daratumumab dosing schedules, which were interpreted as median progression-free survival (PFS) rates of 24 months or higher in all arms (P <.0001 for all arms compared with null hypothesis of median PFS of less than 24 months derived from historical observations). Two-year PFS rates were 89.9% [intense dosing], 82.0% [intermediate dosing], and 75.5% [short dosing], respectively.

“The coprimary endpoint of CR rate of >15% was not met at the time of clinical cutoff, which suggests that single-agent daratumumab may not be sufficient to eradicate [smoldering multiple myeloma]. However, the [progressive disease]/death rate and ORR demonstrated that daratumumab does have single-agent activity in smoldering multiple myeloma,” the study authors explained.

The rates of grade 3 or grade 4 treatment-emergent adverse events were 43.9%, 26.8%, and 15.0% in the intense, intermediate, and short daratumumab scheduling arms, respectively. No new daratumumab-related safety signals were observed.

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Regarding the safety results, the study authors noted that “the intense and intermediate arms had longer treatment durations and therefore extended [adverse effects] collecting periods compared with the short arm, both of which may have contributed to the differences observed in [adverse effect] incidences between treatment arms.”

“The findings of this study suggest that daratumumab has single-agent activity and demonstrates acceptable tolerability in intermediate-risk and high-risk,” the study authors concluded.

This approach is being investigated in an ongoing phase 3 study of patients with high-risk smoldering multiple myeloma.


  1. Landgren CO, Chari A, Cohen YC, et al. Daratumumab monotherapy for patients with intermediate-risk or high-risk smoldering multiple myeloma: A randomized, open-label, multicenter, phase 2 study (CENTAURUS) [published online February 5, 2020]. Leukemia. doi: 10.1038/s41375-020-0718-z
  2. Mateos MV, Hernadez MT, Giraldo P, et al. Lenalidomide plus dexamethasone versus observation in patients with high-risk smoldering multiple myeloa (OuiRedex): long-term follow-up of a randomised controlled, phase 3 trial. Lancet Oncol. 2016;17:1127-1136.

This article originally appeared on Cancer Therapy Advisor