SC Daratumumab Combined with Standard MM Regimens: Open-Label, Multicenter, Phase 2 Study: PLEIADES

A subcutaneous (SC) co-formulation of daratumumab (DARA) with recombinant human hyaluronidase PH20 (rHuPH20; ENHANZE® drug delivery technology, Halozyme, Inc) can be administered in 3 to 5 minutes. A phase 2, open-label, multicenter study called PLEIADES assessed the efficacy and safety of SC DARA (D) combined with lenalidomide, bortezomib, and dexamethasone (RVd), bortezomib, melphalan, and prednisone (VMP), or lenalidomide and dexamethasone (Rd) in patients with newly diagnosed multiple myeloma (NDMM) or relapsed/refractory multiple myeloma (RRMM). 

Patients with transplant-ineligible NDMM received D-VMP, and patients with RRMM with ≥1 prior lines of therapy received D-Rd. Both cohorts were treated until disease progression. Transplant-eligible NDMM patients received 4 cycles of D-RVd induction therapy followed by autologous stem-cell transplant (performed off-study).

The primary efficacy end points were overall response rate (ORR) for D-VMP and D-Rd and rates of very good partial response or better (≥VGPR) for D-RVd. Secondary end points included ≥VGPR for D-VMP and D-Rd, ORR for D-RVd, and complete response or better (≥CR) rate, duration of response, minimal residual disease (MRD)-negativity rate, and DARA serum concentrations for all cohorts. Safety data included rates of treatment-emergent adverse events (TEAEs) and infusion-related reactions (IRRs). 

A total of 199 patients were enrolled in PLEIADES: 67 received D-VMP; 65 received D-Rd; and 57 received D-RVd. As of the data cutoff (March 2019), median duration of follow-up was approximately 7 months for D-VMP and D-Rd and 4 months for D-RVd.

Primary efficacy end points were met for all cohorts. The rate of ORR for D-VMP was 88% (90% confidence interval [CI], 80%-94%) and for D-Rd was 91% (90% CI, 83%-96%).

The rates of ≥VGPR were 72% (90% CI, 61%-81%) for D-RVd, 64% (90% CI, 54%-74%) for D-VMP, and 65% (90% CI, 54%-75%) for D-Rd. The ORR for D-RVd was 97% (90% CI, 91%-99.5%). At the time of the primary analysis, ≥CR rates, duration of response, and MRD-negativity rates were immature.

Rates of any grade IRRs and injection-site reactions were each 7.5% across all cohorts, with no grade 4 reactions in any cohort. Median duration of administration was 5 minutes for all cohorts.

Grade 3 or 4 TEAEs were reported by 69%, 79%, and 58% of patients in the D-VMP, D-Rd, and D-RVd cohorts, respectively. TEAEs leading to treatment discontinuation were <5% in all cohorts. Safety profiles in all cohorts were consistent with intravenous DARA in combination with these standard regimens. 

These findings suggest that SC DARA in combination with standard regimens for multiple myeloma has comparable clinical activity and safety relative to corresponding DARA intravenous regimens, and considerably lower IRR rates and substantially shorter durations of administration.

Abstract OAB-022: 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)

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