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Daratumumab decreases risk for multiple myeloma progression, mortality
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SAN DIEGO — The addition of daratumumab to lenalidomide and dexamethasone reduced the risk for disease progression or death by 45% among patients with transplant-ineligible, newly diagnosed multiple myeloma according to results from a phase 3 randomized trial presented at ASH Annual Meeting and Exposition.
The safety profile of the combination was consistent with previous studies of daratumumab (Darzalex; Janssen, Genmab), a human monoclonal antibody that targets CD38, according to researchers.
“We believe this study has established [the addition daratumumab to lenalidomide and dexamethasone] as a new standard of care for patients who are ineligible for autologous stem cell transplantation,” Thierry Facon, MD, professor of hematology in the department of hematology at Lille University Hospital in Lille, France, said during a presentation.
Previous phase 3 studies showed adding daratumumab to the standard of care of bortezomib (Velcade, Takeda) and dexamethasone for patients with relapsed refractory newly diagnosed multiple myeloma and bortezomib, melphalan and prednisone for transplant-ineligible newly diagnosed multiple myeloma reduced the risk for disease progression or death by 50% or more.
The global study by Facon and colleagues included 737 patients (median age, 73 years; range, 45-90; 52% men) who were ineligible for high-dose chemotherapy with autologous stem cell transplantation due to age or comorbidities.
Researchers randomly assigned patients to 16 mg/kg IV daratumumab (once a week for cycles 1-2, one every 2 weeks for cycles 3-6, and once every 4 weeks thereafter) with 25 mg lenalidomide (Revlimid, Celgene) on days 1 to 21 and 40 mg dexamethasone on days 1, 8, 15 and 22 (n = 368), or lenalidomide and dexamethasone alone (n = 369).
Stratification was based on International Staging System stage, region (North America vs. other) and age.
All patients received 28-day cycles of lenalidomide and dexamethasone with and without daratumumab until disease progression or unacceptable toxicity.
PFS served as the study’s primary endpoint. The secondary endpoints were overall response rate, minimal residual disease negativity rate and safety.
Researchers performed the prespecified interim analysis after 238 PFS events and a median follow-up of 28 months.
The HR for PFS was 0.55 (95% CI, 0.43-0.72). Median PFS for patients who received lenalidomide and dexamethasone was 31.9 months and was not reached in the daratumumab group.
Researchers reported that 19% of patients have died. The HR for OS was 0.78 (95% CI, 0.56-1.1).
Adding daratumumab to the combination of lenalidomide and dexamethasone resulted in complete response or better rate of 47.6% compared with 24.7% in the lenalidomide and dexamethasone group (OR = 2.75, 95% CI, 2.01-3.76). The very good partial response or better rate was 79.3% in the daratumumab group compared with 53.1% in the lenalidomide and dexamethasone group (OR = 3.4, 95% CI, 2.45-4.72).
A greater proportion of patients assigned daratumumab achieved minimal residual disease negativity (24% vs. 7%; P < .0001).
Higher rates — at 5% or more difference — of grade 3 or grade 4 pneumonia (14% vs. 8%), neutropenia (50% vs. 35%) and leukopenia were observed in the daratumumab group. Fatal treatment-related adverse events occurred in 7% of the daratumumab group and 6% of the control group.
“As you can see the PFS for [the addition of daratumumab to lenalidomide and dexamethasone] is very high,” Facon said in a press conference. “The benefit we have in this study is the benefits for patients over the age of 75 years. This regimen is a gentle regimen for elderly or very elderly [patients].” – by John DeRosier
Reference:
Facon T, et al. Abstract LBA-2. Presented at: ASH Annual Meeting and Exposition; Dec. 1-4, 2018; San Diego.
Disclosures: Facon reports board of directors, consultant/advisory or speakers bureau roles with Amgen, Celgene, Janssen, Karyopharm Therapeutics, Oncopeptides Sanofi and Takeda Oncology. Please see the abstract for all other authors’ relevant financial disclosures.