Phase 1 Study Results at ASCO Support First-Line Use of Daratumumab in Multiple Myeloma

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 American Society of Clinical Oncology Annual Meeting, found that including 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 (K) 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 elective discontinuation for allogenic stem cell transplant. The treatment also included 25 mg lenalidomide (Revlimid, R) given on days 1 to 21 and dexamethasone (d), 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, with a median duration of follow-up 7.4 months (range = 4.0-9.3). Six patients (27%) discontinued treatment, with serious adverse events observed in 46% of patients, 14% of which were possibly related to daratumumab.

Eighteen patients (82%) experienced a grade 3/4 treatment-emergent adverse event (TEAE). The most common grade 3/4 TEAEs (more than 10%) were lymphopenia (50%) and neutropenia (23%). No grade 5 TEAE was reported. All daratumumab-associated infusion reactions were less than grade 2.

The authors concluded that the addition of daratumumab to KRd was well tolerated, consistent with that previously reported for KRd, with no additional toxicity observed with the addition of daratumumab. No grade 3/4 toxicities were noted. The treatment was highly effective with 100% overall response rate, as well as a 100% 6-month progression-free survival. The depth of response improved with treatment duration. They claimed that daratumumab can be a feasible option for induction therapy in newly diagnosed patients with multiple myeloma.