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

Br J Haematol. 2021 Mar;192(5):869-878. doi: 10.1111/bjh.16980. Epub 2020 Jul 30.

Abstract

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 71·6% [90% confidence interval (CI) 61·2-80·6%], and the overall response rates (ORRs) for D-VMP and D-Rd were 88·1% (90% CI 79·5-93·9%) and 90·8% (90% CI 82·6-95·9%). With longer median follow-up for D-VMP and D-Rd (14·3 and 14·7 months respectively), responses deepened (ORR: 89·6%, 93·8%; ≥VGPR: 77·6%, 78·5%), and minimal residual disease-negativity (10-5 ) rates were 16·4% and 15·4%. Infusion-related reactions across all cohorts were infrequent (≤9·0%) 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.

Keywords: NDMM; RRMM; combination therapy; daratumumab; subcutaneous.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / adverse effects
  • Antineoplastic Agents, Immunological / administration & dosage
  • Antineoplastic Agents, Immunological / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bortezomib / administration & dosage
  • Combined Modality Therapy
  • Dexamethasone / administration & dosage
  • Female
  • Follow-Up Studies
  • Hematologic Diseases / chemically induced
  • Humans
  • Immunotherapy*
  • Lenalidomide / administration & dosage
  • Male
  • Melphalan / administration & dosage
  • Middle Aged
  • Multiple Myeloma / drug therapy*
  • Prednisone / administration & dosage
  • Standard of Care
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal
  • Antineoplastic Agents, Immunological
  • daratumumab
  • Bortezomib
  • Dexamethasone
  • Lenalidomide
  • Melphalan
  • Prednisone