Subcutaneous (SC) Daratumumab (DARA) in Combination With Standard Multiple Myeloma (MM) Treatment Regimens: An Open-label, Multicenter Phase 2 Study (PLEIADES)

Chari, Ajai; Goldschmidt, Hartmut; San-Miguel, Jesús F.; McCarthy, Helen; Suzuki, Kenshi; Hungria, Vânia; Balari, Anna Sureda; Perrot, Aurore; Hulin, Cyrille; Magen, Hila; Iida, Shinsuke; Maisnar, Vladimír; Karlin, Lionel; Pour, Luděk; Parasrampuria, Dolly A.; Masterson, Tara; Kosh, Michele; Yang, Shiyi; Qi, Ming; Carson, Robin; Moreau, Philippe

doi:10.1016/j.clml.2019.09.023

Cited by 8 publications

(8 citation statements)

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“…After 4 cycles of induction, the GRIFFIN trial reported an ORR 94% and ≥ VGPR 56% [56]. These values are quite similar to those recently reported for the PLEIADES trial which noted an ORR was 97%, with 71.6% of patients achieving a VGPR or better after 4 cycles of induction therapy at the 8 July 2019 clinical cutoff date with only 2 patients discontinuing therapy for toxicity [57]. These data underscore the uniformity of clinical responses between dara-SC and dara-IV.…”

Section: Subcutaneous Daratumumab: Pharmacodynmics Pharmacokinetics supporting

confidence: 83%

“…This population, is analogous to the population treated with dara-IV and Rd in the POLLUX trial (ORR 92.9%, ≥ VGPR 44%) [15]. In comparison, the dara-SC Rd combination showed similar efficacy with an ORR of 93.8% and 64.6% of patients achieving a VGPR or better [57].…”

Section: Subcutaneous Daratumumab: Pharmacodynmics Pharmacokinetics mentioning

confidence: 77%

“…Similarly, the transplant-ineligible NDMM patients were treated with a combination that is analogous to the agents investigated in the ALCYONE trial which evaluated dara-IV and VMP in transplant-ineligible NDMM patients. The ORR with dara-SC VMP was 89.6%, with 64.2% patients achieving a VGPR or better [57]. In comparison the ALCYONE trial reported similar outcomes in the population treated with dara-IV VMP (ORR 90.9%, ≥ VGPR 73%) [17,32].…”

Section: Subcutaneous Daratumumab: Pharmacodynmics Pharmacokinetics mentioning

confidence: 87%

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An evaluation of subcutaneous daratumumab for the treatment of multiple myeloma

Paul

Atrash

Bhutani

et al. 2020

Expert Review of Hematology

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Introduction: A subcutaneous formulation of daratumumab, a human immunoglobulin G1 kappa monoclonal antibody targeting CD38, recently achieved FDA approval for both newly diagnosed and relapsed refractory multiple myeloma amid promises to decrease infusion times and rates of infusion reactions in myeloma patients. Areas covered: In this article the biology behind subcutaneous administration of oncologic antibody therapies is reviewed and the subcutaneous formulation of daratumumab is covered in depth. The most recent results from the PAVO, COLUMBA, and PLEIADES clinical trials evaluating subcutaneous daratumumab as a single agent, and in combination, in both newly diagnosed, and relapsed and refractory myeloma patients are summarized. The efficacy, safety, and PK data from these trials are reviewed, and the potential of the subcutaneous formulation to improve quality of life in myeloma patients and decrease healthcare resource use is discussed. Expert opinion: Subcutaneous daratumumab is non-inferior to conventional intravenous daratumumab with lower risk of infusion-related reactions and decreased administration time. Based on these data, and the recent FDA and European Commission approvalsthe widespread use of the subcutaneous formulation for both conventional and investigational practice is supported.

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Section: Subcutaneous Daratumumab: Pharmacodynmics Pharmacokinetics supporting

confidence: 83%

Section: Subcutaneous Daratumumab: Pharmacodynmics Pharmacokinetics mentioning

confidence: 77%

Section: Subcutaneous Daratumumab: Pharmacodynmics Pharmacokinetics mentioning

confidence: 87%

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An evaluation of subcutaneous daratumumab for the treatment of multiple myeloma

Paul

Atrash

Bhutani

et al. 2020

Expert Review of Hematology

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“…In PLEIADES, DARA SC in combination with SC bortezomib plus lenalidomide/dexamethasone and with SC bortezomib plus melphalan/prednisone in patients with NDMM demonstrated comparable clinical activity and safety to the corresponding DARA IV regimens, with lower rates of IRRs and shorter durations of administration. 41 Although the Cycle 1 Day 1 dose of DARA SC should not be given at home, at-home administration of subsequent doses of DARA SC by a healthcare provider is a possibility for future consideration; however, additional safety follow-up is needed, particularly to further confirm that the risk of severe IRRs with administration beyond Cycle 1 Day 1 is very low or absent.…”

Section: Discussionmentioning

confidence: 99%

Subcutaneous daratumumab in patients with relapsed or refractory multiple myeloma: Part 2 of the open-label, multicenter, dose-escalation phase 1b study (PAVO)

et al. 2020

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Intravenous daratumumab is approved for the treatment of multiple myeloma. In Part 1 of the PAVO study, a mix-and-deliver subcutaneous formulation of daratumumab with recombinant human hyaluronidase PH20 (rHuPH20) was well tolerated, with low rates of infusion-related reactions and similar efficacy to intravenous daratumumab. Part 2 of PAVO evaluated a concentrated, pre-mixed co-formulation of daratumumab and rHuPH20 (DARA SC). Patients with ≥2 prior lines of therapy, including a proteasome inhibitor and immunomodulatory drug, received daratumumab (1800 mg) and rHuPH20 (30,000 U) in 15 mL subcutaneously over 3-5 minutes per the approved intravenous monotherapy dosing schedule. Primary endpoints were daratumumab trough concentration at the end of weekly dosing (just prior to the Cycle 3 Day 1 dose) and safety. Twenty-five patients were enrolled in PAVO Part 2. DARA SC achieved daratumumab trough concentrations similar to or greater than intravenous daratumumab 16 mg/kg. The adverse event profile of DARA SC was consistent with intravenous daratumumab, with no new safety concerns and a lower infusion-related reaction rate. At a median follow-up of 14.2 months, the overall response rate was 52%, median duration of response was 15.7 months, and median progression-free survival was 12.0 months. DARA SC 1800 mg was well tolerated in relapsed/refractory multiple myeloma, with a low infusion-related reaction rate and reduced administration time. Daratumumab serum concentrations following DARA SC were consistent with intravenous dosing, and deep and durable responses were observed. Based on these results, ongoing studies are investigating DARA SC in multiple myeloma and other conditions. (ClinicalTrials.gov identifier: 02519452).

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“…Daratumumab sc has been recently investigated in a phase 2, multicenter study (PLEIADES, MMY2040, NCT03412565) to assess its efficacy and safety with DRd regimen in 65 RRMM patients with ≥1 prior lines of therapy [58]. After a median follow-up of 7 months, ORR was 90.8%, VGPR or better was 64.6%, while ≥CR rates, duration of response, and MRDnegativity rates are immature.…”

Section: Alternative Methods Of Daratumumab Administrationmentioning

confidence: 99%

Monoclonal antibodies in relapsed/refractory myeloma: updated evidence from clinical trials, real-life studies, and meta-analyses

Musto

Rocca

2020

Expert Review of Hematology

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Introduction: In the last few years, monoclonal antibodies have rapidly modified the therapeutic strategies for treating patients with multiple myeloma. Areas covered: In this review, the most recent literature data regarding indications for which monoclonal antibodies are currently or will be shortly approved as salvage therapies in relapsed/refractory myeloma are discussed. In particular, updated results until March 22, 2020 of antibodies directed against CD38 (daratumumab and isatuximab), SLAMF7 (elotuzumab), BCMA (GSK2857916/belantamab mafodotin), and PD-1/PD-1 L axis (nivolumab and pembrolizumab) will be analyzed in detail. Expert opinion: Monoclonal antibodies represent a new, very effective approach that will open novel and dynamic treatment scenarios for myeloma patients in the coming years. Optimal positioning and selection of different antibodies that are or will be soon available, appropriate combinations and careful evaluation of possible new toxicities should be considered in the future management of these patients.

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Subcutaneous (SC) Daratumumab (DARA) in Combination With Standard Multiple Myeloma (MM) Treatment Regimens: An Open-label, Multicenter Phase 2 Study (PLEIADES)

Cited by 8 publications

References 0 publications

An evaluation of subcutaneous daratumumab for the treatment of multiple myeloma

An evaluation of subcutaneous daratumumab for the treatment of multiple myeloma

Subcutaneous daratumumab in patients with relapsed or refractory multiple myeloma: Part 2 of the open-label, multicenter, dose-escalation phase 1b study (PAVO)

Monoclonal antibodies in relapsed/refractory myeloma: updated evidence from clinical trials, real-life studies, and meta-analyses

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