The Pleiades study assessed subcutaneous (SC) versus intravenous (IV) administration of daratumumab and found that SC administration in combination with standard-of-care regimens demonstrated comparable clinical activity and safety to IV daratumumab regimens, with considerably lower infusion-related reactions (IRRs) and shorter durations of administration, in patients with multiple myeloma (MM), according to data presented at the 2019 ASH Annual Meeting.
This open-label, multicenter, phase II study included 199 transplant-ineligible patients with newly diagnosed MM who received SC daratumumab in combination with bortezomib, lenalidomide, and dexamethasone (D-VRd; n=67) or daratumumab plus bortezomib, melphalan, and prednisone (D-VMP; n=67). There was an additional cohort of patients with relapsed/refractory MM who received daratumumab plus lenalidomide and dexamethasone (D-Rd; n=65).
At data cutoff (July 8, 2019), median duration of follow-up was 11.0 months with D-VMP, 11.2 months with D-Rd, and 7.1 months with D-VRd.
The overall response rate (primary endpoint for D-VMP and D-Rd cohorts) was 89.6% for D-VMP (90% confidence interval [CI], 81.3-95.0) and 93.8% for D-Rd (90% CI, 86.5-97.9). The rate of very-good partial response or better was 70.1% for D-VRd (90% CI, 59.6-79.3; primary endpoint for this cohort). The researchers noted that these response rates were similar to the ALCYONE and POLLUX trials, which assessed IV daratumumab plus VMP and Rd regimens, respectively.
Median duration of SC daratumumab administration was five minutes in all cohorts for the first, second, and all subsequent injections. Safety outcomes were consistent with known adverse events associated with IV daratumumab in combination with various standard-of-care regimens. IRR and injection-site reaction rates were consistent with SC daratumumab monotherapy outcomes observed in the COLUMBA study. The pharmacokinetics of SC daratumumab in combination with each regimen were also consistent with historical data and immunogenicity from previous reports on daratumumab.
Chari A, San-Miguel J, McCarthy H, et al. Subcutaneous daratumumab plus standard treatment regimens in patients with multiple myeloma across lines of therapy: Pleiades study update. Abstract 3152. Presented at the 2019 ASH Annual Meeting, December 8, 2019; Orlando, Florida.