Daratumumab regimen improves survival in transplant-ineligible multiple myeloma
Key takeaways:
- The addition of subcutaneous daratumumab to triplet therapy improved outcomes in transplant-ineligible or -deferred multiple myeloma.
- The regimen reduced risk for disease progression or death by 43%.
The addition of subcutaneous daratumumab to triplet therapy improved outcomes for certain patients with newly diagnosed multiple myeloma, study results showed.
The findings, published in Nature Medicine, support quadruplet therapy with subcutaneous daratumumab (Darzalex Faspro, Johnson & Johnson/Janssen), bortezomib (Velcade, Takeda), lenalidomide (Revlimid, Bristol Myers Squibb) and dexamethasone as a new standard of care for patients with transplant-ineligible or transplant-deferred multiple myeloma, researchers concluded.
“Daratumumab is the first monoclonal antibody that had shown single-agent clinical activity in multiple myeloma, [but it] has not moved to frontline treatment in combination with other standard-of-care treatments,” Saad Z. Usmani, MD, MBA, FACP, FASCO, myeloma specialist and cellular therapist at Memorial Sloan Kettering Cancer Center and a Healio | HemOnc Today Editorial Board member, told Healio. “This combination could redefine frontline treatment for transplant-ineligible patients by providing a more potent, durable and tolerable regimen.”
Triplet therapy with bortezomib, lenalidomide and dexamethasone — a regimen often referred to as VRd — is a current standard of care for patients with newly diagnosed multiple myeloma, including those eligible or ineligible for autologous stem cell transplantation.
In the randomized phase 3 CEPHEUS trial, Usmani and colleagues evaluated the safety and efficacy of adding subcutaneous daratumumab to VRd for patients ineligible for transplant.
The analysis included 395 patients aged 31 to 80 years who enrolled at 92 sites in 13 countries.
The researchers randomly assigned 197 of them (median age, 70 years; 44.2% men; 82.2% white) to eight cycles of VRd plus subcutaneous daratumumab. The other 198 (median age, 70 years; 56.1% men; 78.8% white) received VRd alone.
Overall minimal residual disease (MRD)-negativity rate at 10-5 by next-generation sequencing served as the primary endpoint. Secondary endpoints included rate of complete response or better, PFS and sustained MRD-negativity rate at 10-5.
After median follow-up of 58.7 months, a higher percentage of patients assigned daratumumab achieved complete response or better (81.2% vs 61.6%; P < .0001), MRD negativity (60.9% vs 39.4%; OR = 2.37; 95% CI, 1.58-3.55), and at least 12 months of sustained MRD negativity (48.7% vs 26.3%; P < .0001).
The daratumumab group also had a 43% lower risk for disease progression or death (HR = 0.57; 95% CI, 0.41-0.79).
“The addition of daratumumab to VRd demonstrated improvement in both depth of response measured by MRD assay and progression free survival, which was important to see in this older patient population that are considered mostly to be fit or intermediate-fit by the [International Myeloma Working Group] frailty score criteria,” Usmani said.
Adverse events — which included neutropenia and thrombocytopenia — appeared consistent with those observed in prior studies of daratumumab and VRd.
The researchers acknowledged study limitations. For example, patients who identify as Black or African American comprised only 4.8% of the CEPHEUS trial population, which may be an underrepresentation for some countries included in the analysis.
Also, not all countries with trial sites have regulations about reporting participants’ race. Race data had not been reported for approximately 7% of the study population.
“It would be important to examine the role of treatment de-escalation in the future studies once [patients with] newly diagnosed multiple myeloma have had sustained MRD negativity for a certain period,” Usmani told Healio. “There are several trials already underway to help define that duration of therapy.”
For more information:
Saad Z. Usmani, MD, MBA, FACP, FASCO, can be reached at usmanis@mskcc.org.
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