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Author Notes:

JESUS SAN-MIGUEL, sanmiguel@unav.es

All authors developed the manuscript, provided final submission approval, and confirmed that the protocol was followed and that the data were accurate and complete.

The authors would like to thank the patients who participated in this study and their families, as well as the study co-investigators, research nurses, and coordinators at each of the clinical sites. Medical writing and editorial support were provided by Kristin Runkle, PhD, of MedErgy, and were funded by Janssen Global Services, LLC.

JS-M has acted as a consultant for Amgen, Bristol Myers Squibb, Celgene, Janssen, Merck, Novartis, Takeda, Sanofi, and Roche. SZU has acted as a consultant for AbbVie, GlaxoSmithKline, Celgene, Amgen/Onyx, Takeda/Millennium, Sanofi, Seattle Genetics, Skyline, Merck, and Janssen; has received research funding from Celgene, Amgen/Onyx, Takeda/Millennium, Sanofi, Seattle Genetics, Skyline, Merck, Janssen, Array BioPharma, and Pharmacyclics; has served on speakers’ bureaus for Celgene, Amgen, Janssen, Sanofi, and Takeda; and has received travel expenses from Janssen, Celgene, Amgen, and Takeda. M-VM has received honoraria from and has acted as a consultant for Celgene, Janssen, Takeda, and Amgen. NWCJvdD has received research support from Janssen Pharmaceuticals, Amgen, Celgene, Novartis, and Bristol Myers Squibb and has served on advisory boards for Janssen Pharmaceuticals, Amgen, Celgene, Bristol Myers Squibb, Novartis, Bayer, Takeda, and Servier. JLK has acted as a consultant or served in an advisory role for Janssen, Takeda, Celgene, Bristol Myers Squibb, Karyopharm Therapeutics, TG Therapeutics, Sanofi, Amgen, and Tecnofarma; has received research funding (institutional) from Merck, Celgene, Janssen, Sutro Biopharma, Fortis Therapeutics, Amgen, AbbVie/Genentech, and Bristol Myers Squibb; and has received travel and accommodation expenses from Janssen, Celgene, Bristol Myers Squibb, Sanofi, Amgen, and Takeda. PM has acted as a consultant for and received honoraria from Celgene, Takeda, and Janssen. AO has acted as a consultant for and received honoraria from Amgen, Takeda, and Janssen and has served on speakers’ bureaus for Amgen, Celgene, and Janssen. TP has received research support from Janssen Pharmaceuticals and served on advisory boards for Janssen Pharmaceuticals, Celgene, Takeda, and Behring. LB has acted as a consultant for and received honoraria from Takeda, Celgene, Janssen, and Amgen and has received travel expenses from Janssen, Celgene, and Amgen. KL, PH, TM, PLC, ML, and AF are employees of Janssen. PH, TM, PLC, ML, and AF hold stock in Johnson & Johnson. AC has acted as a consultant for Amgen, Array BioPharma, Celgene, Janssen, Millennium, Takeda, and Novartis and has received research funding from Amgen, Array BioPharma, Celgene, Janssen, Millennium, Takeda, Novartis, and Pharmacyclics. HN has no conflicts of interest to report.

Subjects:

Research Funding:

The study was registered at ClinicalTrials.gov (NCT02519452) and was sponsored by Janssen Research & Development, LLC. Medical writing and editorial support were funded by Janssen Global Services, LLC. The data-sharing policy of Janssen Pharmaceutical Companies of Johnson & Johnson is available at https://www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through the Yale Open Data Access (YODA) Project site at http://yoda.yale.edu.

This study was sponsored by Janssen Research & Development, LLC.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Hematology
  • ANTIBODY DARATUMUMAB
  • DEXAMETHASONE
  • MONOTHERAPY
  • PHARMACOKINETICS
  • LENALIDOMIDE
  • INFUSION
  • CD38

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

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Journal Title:

HAEMATOLOGICA

Volume:

Volume 106, Number 6

Publisher:

, Pages 1725-1732

Type of Work:

Article | Final Publisher PDF

Abstract:

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 an efficacy similar to that of intravenous daratumumab. Part 2 of PAVO evaluated a concentrated, pre-mixed co-formulation of daratumumab and rHuPH20 (DARA SC). Patients who had received two or more prior lines of therapy, including a proteasome inhibitor and an immunomodulatory drug, were given daratumumab (1,800 mg) and rHuPH20 (30,000 U) in 15 mL subcutaneously over 3 to 5 minutes as per the approved intravenous monotherapy dosing schedule. Primary endpoints were daratumumab trough concentration at the end of weekly dosing (just prior to the day 1 dose of cycle 3) and safety. Twenty-five patients were enrolled in PAVO part 2. DARA SC achieved daratumumab trough concentrations similar to or greater than those achieved with intravenous daratumumab 16 mg/kg. The adverse event profile of DARA SC was consistent with that of 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%, the median duration of response was 15.7 months, and the median progression-free survival was 12.0 months. DARA SC 1,800 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 those following intravenous dosing, and deep and durable responses were observed. Based on these results, ongoing studies are investigating DARA SC in the treatment of multiple myeloma and other conditions.

Copyright information:

© 2021 Ferrata Storti Foundation

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (https://creativecommons.org/licenses/by-nc/4.0/rdf).
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