A subcutaneous formulation of daratumumab, plus standard-of-care treatment, led to response rates that were similar to those seen with intravenous daratumumab in patients with newly diagnosed and previously untreated multiple myeloma (MM), according to results from the phase II multicenter PLEIADES trial. However, the subcutaneous route of administration was associated with lower infusion-related reactions (IRRs) and shorter durations of administration.
Ajai Chari, MD, from the Icahn School of Medicine at Mount Sinai in New York, presented the findings at the 17th International Myeloma Workshop.
Earlier this year, results from the phase III COLUMBA trial demonstrated that a subcutaneous formulation of daratumumab could shorten the treatment time from hours to minutes, compared with the conventional intravenous route of administration, while maintaining the original formulation’s efficacy and tolerability. The PLEIADES trial uses the same subcutaneous formulation of daratumumab – co-formulated with recombinant human hyaluronidase PH20 (rHuPH20) – but evaluates its safety and efficacy in an expanded patient population of those with previously untreated MM. The study’s primary efficacy endpoints were overall response rate (ORR) and the rate of very good partial response or better (≥VGPR).
The researchers evaluated outcomes in three treatment cohorts:
- patients with newly diagnosed, transplant-ineligible MM: daratumumab plus bortezomib, melphalan, and prednisone (D-VMP; n=67)
- patients with relapsed/refractory MM: daratumumab plus lenalidomide and dexamethasone (D-Rd; n=65)
- patients with newly diagnosed, transplant-eligible MM: daratumumab plus bortezomib, lenalidomide, and dexamethasone (D-VRd) induction (n=67)
Across all cohorts, the median duration of administration was five minutes (range not provided). As of the data cutoff (March 4, 2019), the median duration of follow-up was approximately seven months in the D-VMP and D-Rd groups, and four months for the D-VRd group (ranges not provided).
All cohorts had met the primary endpoints at follow up, with ORRs of:
- D-VMP: 88.1% (90% CI 79.5%-93.9%)
- D-Rd: 90.8% (90% CI 82.6%-95.9%)
- D-VRd: 97% (90% CI 90.9%-99.5%)
In the D-VRd group, the rate of ≥VGPR was 71.6%, while the D-VMP group had a ≥VGPR rate of 64.2% and the D-Rd group had a ≥VGPR rate of 64.6%.
At the time of data presentation, rates of complete response, duration of response, and measurable residual disease–negativity rates were immature and thus not presented.
Adverse events (AEs) were reported by: 46 patients in the D-VMP group (68.7%), 51 patients in the D-Rd group (78.5%), and 39 patients in the D-VRd group (58.2%), respectively. “Rates of any grade IRRs and injection-site reactions were each 7.5% across all cohorts,” the authors wrote, including one grade 3 IRR with D-VRd, but no grade 4 reactions in any cohort. In addition, the authors noted that the safety profile of the subcutaneous formulation was consistent with standard-of-care backbone regimens for MM.
Few of the AEs led to treatment discontinuation, with discontinuation rates below 5% in each cohort.
Rates of Grade 3 or 4 AEs were:
- D-VMP: 68.7%
- D-Rd: 78.5%
- D-VRd: 58.2%
Limitations of the study include the small patient sample sizes for each treatment cohort, as well as the relatively short duration of follow-up and lack of detailed response rates or duration.
Chari A, Goldschmidt H, San-Miguel J, et al. Subcutaneous (SC) daratumumab (DARA) in combination with standard multiple myeloma (MM) treatment regimens: an open-label, multicenter phase 2 study (PLEIADES). Abstract OAB-022. Presented at the 17th International Myeloma Workshop, September 13, 2019; Boston, Massachusetts.