Phase 1 Study Results at ASCO Support First-Line Use of Daratumumab in Multiple Myeloma
Surabhi Dangi-Garimella, PhD
A COMBINATION OF PROTEASOME inhibitors and immunomodulatory drugs in the standard of care has improved outcomes in patients with multiple myeloma over the past 10 years. However, these patients can relapse even after complete remission in first-line indications. A phase 1 study, presented at the 2017 Annual Meeting of the American Society of Clinical Oncology, found that using daratumumab, an antibody that binds and inhibits the CD38 receptor, can improve patient response to treatment.
The trial enrolled newly diagnosed patients, regardless of transplantation eligibility. Patients were administered daratumumab at 16 mg/kg weekly for cycles 1 and 2, every other week for cycles 3 to 6, and once in 4 weeks thereafter. Carfilzomib was administered on days 1, 8, and 15 of each 28-day cycle (20 mg/m2 on day 1 of cycle 1 and 36 mg/m2 or 70 mg/m2 based on tolerability of first dose), for most of the 13 cycles, or treatment was discontinued for allogenic stem cell transplant. The treatment also included 25-mg lenalidomide given on days 1 to 21 and dexamethasone 20 to 40 mg weekly. The primary endpoint for this very early phase trial was tolerability.
Twenty-two patients received a median of 8 (range, 1-10) treatment cycles and were followed for a median of 7.4 months (range, 4.0-9.3). Six patients (27%) discontinued treatment, with serious adverse events (AEs) observed in 46% of patients, 14% of which were thought to be related to daratumumab. Grade 3/4 treatment-emergent AEs (TEAE) were observed in 18 (82%) patients: lymphopenia (50%) and neutropenia (23%) were most common. No grade 5 TEAEs were reported.
The authors concluded that daratumumab with carfilzomib and lenalidomide was well tolerated, consistent with results previously reported for carfilzomib plus lenalidomide, with no additional toxicity observed. They claimed that daratumumab can be a feasible option for induction therapy in newly diagnosed patients with multiple myeloma. No grade 3/4 toxicities were noted. The treatment was highly effective, with a 100% overall response rate as well as a 100% 6-month progression-free survival. The depth of response improved with treatment duration.