CEPHEUS: Further Support for Daratumumab-Regimens in Untreated MM

Dec 30, 2024

Daratumumab plus bortezomib, lenalidomide, and dexamethasone (VRd) outperformed VRd alone in terms of MRD-negativity rates and sustained MRD-negativity rates in patients with previously untreated multiple myeloma (MM) and ineligible for transplant or not planned to receive a transplant. These findings support daratumumab in combination with VRd as a standard therapy for newly diagnosed MM.

The randomized, phase 3 CEPHEUS trial (NCT03652064) evaluated daratumumab plus VRd compared with VRd alone in patients with newly diagnosed MM (n=395). The primary endpoint of MRD-negativity (10^-5) plus complete response or better (≥CR) was met, with rates of 60.9% and 39.4% in the daratumumab arm and control arm, respectively (OR 2.37; 95% CI 1.58–3.55; P<0.0001)¹. Now, Sonja Zweegman, MD, PhD, from the Amsterdam University Medical Center, in the Netherlands has presented an expanded analysis of MRD outcomes².

At 12 months, MRD-negativity (10^-5) plus greater than or equal to CR rates were 43.1% and 28.3% in the experimental arm and control arm, respectively. At 48 months, the corresponding rates were 60.9% and 38.4%. Furthermore, MRD-negativity (10^-6) plus greater than or equal to CR was documented in 22.8% of the participants on daratumumab at 12 months, whereas only 11.1% of the participants without daratumumab in their treatment regimen reached this endpoint. At 48 months, the daratumumab arm still delivered higher rates for this endpoint than the control arm (45.2% vs 27.3%). Thus, adding daratumumab to VRd improved MRD-negativity across cut-offs, plus greater than or equal to CR rates, at all-time points. “Note that daratumumab almost doubled 12, 24, and 36-month sustained MRD-negativity plus greater than or equal to CR rates,” said Dr. Zweegman.

“CEPHEUS is the fifth phase 3 study in newly diagnosed MM demonstrating the beneficial effect of daratumumab added to standard of care regimens,” concluded Dr. Zweegman. “The current MRD data further supports daratumumab plus VRd as a standard therapy for patients with previously untreated MM and transplant-ineligible or for whom transplant was deferred.”

Medical writing support was provided by Robert van den Heuvel.

Author

Teresa Sellinger

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REFERENCES & ADDITIONAL READING

Usmani S, et al. 21^st IMS Annual Meeting, 25–28 September 2024, Rio de Janeiro, Brazil.
Zweegman S, et al. Daratumumab plus bortezomib, lenalidomide, and dexamethasone (VRd) versus VRd alone in patients with newly diagnosed multiple myeloma ineligible for SCT or for whom SCT is not planned as initial therapy: analysis of minimal residual disease in the phase 3 CEPHEUS trial. Abstract 362, 66^th ASH Annual Meeting, 7–10 December 2024, San Diego, CA, USA.