Adding Daratumumab to the Treatment Regimen Improves Progression-Free Survival in Patients with Multiple Myeloma
Daratumumab in combination with lenalidomide and dexamethasone achieved a 63% reduction in progression-free survival (PFS) compared with lenalidomide and dexamethasone alone in patients with multiple myeloma who had received at least 1 previous line of therapy, according to study results presented at the 2016 European Hematology Association Annual Congress meeting.
The open-label, phase 3 POLLUX study randomized 569 patients (median age, 65 years) to treatment with daratumumab in combination with lenalidomide and dexamethasone (ie, the treatment group) or to treatment with lenalidomide and dexamethasone alone (ie, the control group).
All patients received 25 mg of lenalidomide daily for the first 21 days of the 28-day cycle and 4 mg of dexamethasone weekly. The patients in the treatment group also received daratumumab 16 mg/kg once weekly during treatment cycles 1 and 2; every 2 weeks during treatment cycles 3 to 6; and once on the first day of treatment cycles 7 and onward. The treatment was continued until disease progression, unacceptable toxicity, or patient withdrawal.
The patients received previous treatment with proteasome inhibitors (86%); immunomodulatory agents (55%); or a proteasome inhibitor and immunomodulatory agents (44%), with 27% of all patients refractory to their last line of previous therapy.
At a median follow-up of 13.5 months, the treatment group had a significantly improved median PFS (63%) and a significantly increased overall response rate compared with the control group (93% vs 76%, respectively; P <.0001). The time to progression in the treatment group was also significantly delayed compared with the control group (P <.0001). In addition, the rates of complete responses or better and very good partial responses or better were doubled in the treatment group (43% vs 19%, respectively; P <.0001 and 76% vs 44%, respectively; P <.0001).
The trial was unblinded after meeting its primary end point of improved PFS. After recommendations from an independent data monitoring committee, the patients in the control group were offered the option to receive daratumumab after confirmed disease progression.
The most common adverse events were neutropenia, diarrhea, fatigue, upper respiratory tract infection, anemia, constipation, cough, thrombocytopenia, and muscle spasms. The most common grade 3/4 treatment adverse events were neutropenia, thrombocytopenia, and anemia. The rates of discontinuation as a result of adverse events were similar for the treatment and control groups (7% and 8%, respectively).
The safety of daratumumab in combination with lenalidomide and dexamethasone was consistent with the safety profile of daratumumab alone and the safety profiles of each drug.
The investigators concluded that daratumumab combined with lenalidomide and dexamethasone could potentially represent a new standard of care for patients with multiple myeloma who have received at least 1 previous line of therapy.