The phase III ALCYONE study showed that daratumumab in combination with bortezomib, melphalan, and prednisone is a viable front-line option for myeloma patients who are not candidates for ASCT.
Newly diagnosed multiple myeloma patients who are not considered candidates for autologous stem cell transplantation (ASCT) may soon have a treatment alternative. Recently, Genmab A/S announced positive results from the phase III ALCYONE study of daratumumab in combination with bortezomib, melphalan, and prednisone (VMP) vs VMP alone as front-line treatment.
Patients in this study were randomized to receive 9 cycles of either daratumumab combined with VMP or VMP alone. In the daratumumab treatment arm, patients received 16 mg/kg of daratumumab once weekly for 6 weeks, followed by once every 3 weeks. Following the 9 cycles, patients in the daratumumab treatment arm continued to receive 16 mg/kg of daratumumab once every 4 weeks until disease progression.
The study met the primary endpoint of improving progression free survival (PFS) at a pre-planned interim analysis (hazard ratio = 0.50). Treatment with daratumumab reduced the risk of disease progression or death by 50% compared with those patients who did not receive daratumumab. The median PFS for patients treated with daratumumab in combination with VMP has yet to be reached. The estimated median PFS was 18.1 months for patients who received VMP alone.
“We hope the broader dataset will be presented at a scientific meeting in the coming time,” a spokesperson for the company told OncoTherapy Network.
Overall, the safety profile of daratumumab in combination with VMP was reported to be consistent with the known safety profile of both the VMP regimen and daratumumab. This agent is already approved in the United States in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of patients with multiple myeloma who have received at least one prior therapy.
In addition, daratumumab is approved in combination with pomalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor (PI). It is approved as a monotherapy for the treatment of patients with multiple myeloma who have received at least three prior lines of therapy, including a PI and an immunomodulatory agent, or who are double-refractory to a PI and an immunomodulatory agent.
The current phase III study (NCT02195479) is a randomized, open-label, multicenter study and includes 706 newly diagnosed patients with multiple myeloma, who were not considered candidates for ASCT. Based on the new results, an Independent Data Monitoring Committee recommended the data be unblinded. Further analyses of the safety and efficacy data are now underway. Janssen Biotech, Inc., which licensed daratumumab from Genmab in 2012, is working on the approval application.
Additional studies are ongoing or planned to assess daratumumab’s potential in other malignant and premalignant diseases on which CD38 is expressed, such as smoldering myeloma, natural killer T-cell lymphoma, amyloidosis, myelodysplastic syndromes, and solid tumors.