Subcutaneous daratumumab plus standard treatment regimens in patients with multiple myeloma across lines of therapy (PLEIADES): an open-label Phase II study

Daratumumab is a CD38-targeting monoclonal antibody approved for intravenous (IV) infusion for multiple myeloma (MM). We describe the Phase II PLEIADES study of a subcutaneous formulation of daratumumab (DARA SC) in combination with standard-of-care regimens: DARA SC plus bortezomib/lenalidomide/dexamethasone (D-VRd) for transplant-eligible newly diagnosed MM (NDMM); DARA SC plus bortezomib/melphalan/prednisone (D-VMP) for transplant-ineligible NDMM; and DARA SC plus lenalidomide/dexamethasone (D-Rd) for relapsed/refractory MM. In total, 199 patients were treated (D-VRd,n = 67; D-VMP,n = 67; D-Rd,n = 65). The primary endpoints were met for all cohorts: the >= very good partial response (VGPR) rate after four 21-day induction cycles for D-VRd was 71 center dot 6% [90% confidence interval (CI) 61 center dot 2-80 center dot 6%], and the overall response rates (ORRs) for D-VMP and D-Rd were 88 center dot 1% (90% CI 79 center dot 5-93 center dot 9%) and 90 center dot 8% (90% CI 82 center dot 6-95 center dot 9%). With longer median follow-up for D-VMP and D-Rd (14 center dot 3 and 14 center dot 7 months respectively), responses deepened (ORR: 89 center dot 6%, 93 center dot 8%; >= VGPR: 77 center dot 6%, 78 center dot 5%), and minimal residual disease-negativity (10(-5)) rates were 16 center dot 4% and 15 center dot 4%. Infusion-related reactions across all cohorts were infrequent (<= 9 center dot 0%) and mild. The median DARA SC administration time was 5 min. DARA SC with standard-of-care regimens demonstrated comparable clinical activity to DARA IV-containing regimens, with low infusion-related reaction rates and reduced administration time.