Researchers examined adding daratumumab to standard of care in newly diagnosed transplant-ineligible myeloma patients.
Adding daratumumab to lenalidomide and dexamethasone (D-Rd) in patients with newly diagnosed transplant-ineligible multiple myeloma significantly decreased the risk of disease progression and death by 45% vs a regimen of lenalidomide and dexamethasone alone (Rd). Results of the study (LBA-2) were presented at the 2018 American Society of Hematology (ASH) Annual Meeting & Exposition, held December 1–4 in San Diego.
Lenalidomide-based therapies are a standard of care for patients with newly diagnosed transplant-ineligible multiple myeloma. Daratumumab is a human monoclonal antibody that binds to CD38 and shows single-agent activity in heavily pretreated multiple myeloma patients. In previous phase III studies, the addition of daratumumab to standard of care in relapsed/refractory or transplant-ineligible multiple myeloma patients yielded a ≥ 50% reduction in the risk of disease progression or death. Due to the efficacy and tolerable safety profile of D-Rd, study researchers led by Thierry Facon, MD, of HÃ´pital Claude Huriez in Lille, France, examined D-Rd vs Rd in patients with this type of multiple myeloma.
The researchers randomized 737 patients (median age, 73 years) in a 1:1 ratio to either the Rd arm or the D-Rd arm. Patients were treated to the point of disease progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS), and key secondary endpoints included overall response rate and safety.
According to results of a prespecified interim analysis after 239 PFS events, with a median follow-up of 28 months, the researchers discovered that the hazard ratio (HR) for PFS was 0.55 (95% CI, 0.43–0.72; P < .0001), translating to a 45% reduction in disease progression or death in patients administered D-Rd vs those administered Rd alone. Median PFS was 31.9 months in the RD arm and not reached in the D-Rd arm. In addition, D-Rd yielded deeper responses, with a complete response or better rate of 47.6% vs 24.7% in the Rd arm (odds ratio, 2.75; 95% CI, 2.01–3.76; P < .0001). The very good partial response rate was also higher in the D-Rd arm. The HR for overall survival was 0.78 (95% CI, 0.56–1.1), and 19% of patients died in the study. Follow-up is ongoing. The safety profile for D-Rd was similar to that of daratumumab studies previously reported in the literature, with no new safety signals noted.
“These data together with the phase III ALCYONE study [daratumumab, bortezomib, melphalan, and prednisone vs bortezomib, melphalan, and prednisone] support the addition of daratumumab to standard-of-care combinations in patients with [newly diagnosed multiple myeloma] ineligible for transplant,” concluded the researchers.
In an interview with Cancer Network, Mark Crowther, MD, MSc, chair and professor of medicine at McMaster University, shared why he and fellow experts found the results of this study exciting. “Daratumumab is a cool additional new therapy, which is relatively nontoxic [and] produced really impressive outcomes in this study,” he said. “Daratumumab is a recently designed intervention that is added on to traditional therapies and results in impressive improvements in outcomes in a disease that used to be viewed as being incurable, and oftentimes-in the more distant past-as progressive to death in all cases.”
Crowther said one potential drawback to the current study is its timeliness, which is a concern that crops up in even the best hematology-oncology studies-studies that take years to design, conduct, and disseminate. “There are a vast number of innovations in myeloma treatment going on right now, and so the question is going to be which of these treatments becomes the standard,” he said. “In a lot of cases, these studies take years to put together; the field has moved beyond these studies. There is no doubt authors would argue that this study is somewhat out of date because the comparison arm ... may not be what is used in a lot of centers. [Nevertheless], in the slow march of science and hematology, this is a very interesting additional treatment strategy that will help people with what would otherwise be a terrible disease.”