Last year daratumumab (Darzalex) received accelerated approval by the U.S. Food and Drug Administration to treat myeloma patients that had at least three prior therapies. Daratumumab was the first human monoclonal antibody to be approved for the treatment of myeloma. Last month this antibody therapy received approval by the European Commission. The approvals were based on clinical findings that Daratumumab administered as a single agent demonstrated an overall response rate of 30% and a median overall survival of 20 months in a patient population that had received at least 5 lines of prior therapy and were double refractory to both proteasome inhibitors and iMiDs.
At a plenary session on Sunday at ASCO, Dr. Antonio Palumbo from the University of Torino presented the most recent findings from the CASTOR Phase III randomized trial testing Daratumumab (D) in combination with bortezomib (V), and dexamethasone (d) referred to as DVd versus bortezomib and dexamethasone (Vd) in patients with relapsed or refractory multiple myeloma who had received > 1 line of prior therapy. Approximately 500 patients were enrolled in this large Phase III trial (251 in the DVd arm and 247 in the Vd arm) with similar patient disposition and demographics in each of the two arms. The major conclusions from the CASTOR study indicated that patients receiving DVd demonstrated significant improvements in progression free survival (PFS), time to progression (TTP), and overall response rate in comparison to patients receiving Vd alone. More specifically this translated to a 61% reduction in the risk of disease progression in the DVd group vs the Vd group. The improvements were even more dramatic for lower risk patients (ISS1) and in patients who had received fewer lines of treatment. In particular, when DVd was administered as a second line therapy, PFS at 1 year was in 77% of patients receiving DVd versus 22% of Vd treated patients. The rates of VGPR and CR were doubled with DVd and patients who were negative for the very sensitive Minimal Residual Disease measurement were 5 times higher in the DVd group when compared to the Vd group. With respect to adverse events there was a slightly higher rate of thrombocytopenia in DVd treated patients and similar numbers of other common toxicities including anemia, lowered blood counts, pneumonia and hypertension. Infusion reactions were observed in .98% of patients receiving DVd, but only during the first infusion.
Dr. Palumbo concluded by saying that this regimen should be considered a new Standard of Care for patients receiving Velcade and Dexamethasone. During the follow-up discussion by Dr. Paul Richardson from Dana Farber Cancer Institute it was mentioned that promising data from another Daratumumab combination trial, POLLUX, which compares Daratumumab plus Revlimid and dexamethasone versus Revlimid and dexamethasone alone will be presented at the upcoming European Hematology Association Meeting that will take place between June 9th to 12th. Therefore stay tuned for more exciting news on promising novel combination approaches that are being tested to treat myeloma patients.