CEPHEUS
Trial question
What is the effect of daratumumab plus bortezomib, lenalidomide, and dexamethasone in patients with transplant-ineligible or transplant-deferred newly diagnosed multiple myeloma?
Study design
Multi-center
Open label
RCT
Population
Characteristics of study participants
50.0% female
50.0% male
N = 395
395 patients (197 female, 198 male).
Inclusion criteria: patients with transplant-ineligible or transplant-deferred newly diagnosed multiple myeloma.
Key exclusion criteria: prior therapy for multiple myeloma other than a short course of corticosteroids; prior or concurrent invasive malignancy within 5 years of randomization; grade ≥ 2 peripheral neuropathy or neuropathic pain; focal radiotherapy within 14 days of randomization; plasmapheresis within 28 days of randomization; clinical signs of meningeal involvement of multiple myeloma.
Interventions
N=197 D-VRd (subcutaneous daratumumab plus bortezomib, lenalidomide, and dexamethasone).
N=198 VRd (bortezomib, lenalidomide, and dexamethasone).
Primary outcome
Percentage of patients achieving minimal residual disease-negativity status
60.9%
39.4%
60.9 %
45.7 %
30.4 %
15.2 %
0.0 %
D-VRd
VRd
Significant
increase ▲
NNT = 4
Significant increase in the percentage of patients achieving minimal residual disease-negativity status (60.9% vs. 39.4%; OR 2.37, 95% CI 1.58 to 3.55).
Secondary outcomes
Significant increase in complete response or better (81.2% vs. 61.6%; OR 2.73, 95% CI 1.71 to 4.34).
Significant increase in the rate of sustained minimal residual disease-negativity rate for ≥ 12 months (48.7% vs. 26.3%; OR 2.63, 95% CI 1.73 to 4).
Significant increase in median progression-free survival at 54 months (68.1% vs. 49.5%; HR 1.75, 95% CI 1.27 to 2.44).
Safety outcomes
No significant differences in diarrhea, peripheral sensory neuropathy, lymphopenia.
Conclusion
In patients with transplant-ineligible or transplant-deferred newly diagnosed multiple myeloma, D-VRd was superior to VRd with respect to the percentage of patients achieving minimal residual disease-negativity status.
Reference
Saad Z Usmani, Thierry Facon, Vania Hungria et al. Daratumumab plus bortezomib, lenalidomide and dexamethasone for transplant-ineligible or transplant-deferred newly diagnosed multiple myeloma: the randomized phase 3 CEPHEUS study. Nat Med. 2025 Feb 5. Online ahead of print.
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