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Subcutaneous daratumumab for RRMM: PAVO part 2
burden for patients and healthcare providers.
Findings from PAVO on the safety, PK, and efficacy pro- file of DARA SC informed four ongoing phase III studies of DARA SC 1,800 mg.36-39 In the randomized, multicenter, open-label, non-inferiority study, COLUMBA, DARA SC demonstrated non-inferiority to DARA 16 mg/kg IV in terms of ORR and maximum Ctrough on day 1 of cycle 3, with a similar safety profile and a significantly reduced IRR rate, in patients with RRMM.36 Patient-reported outcome data from COLUMBA indicated that patients receiving DARA SC were more satisfied with their cancer therapy and had more positive perceptions of their treatment than patients receiving IV daratumumab.40 The efficacy and safe- ty of DARA SC are also being investigated in combination with standard-of-care regimens in the phase II PLEIADES study, and results from this study demonstrate the feasibil- ity of administering DARA SC in combination with stan- dard-of-care regimens containing SC bortezomib. In PLEIADES, DARA SC in combination with SC bortezomib plus lenalidomide/dexamethasone and with SC borte- zomib plus melphalan/prednisone in patients with newly diagnosed MM demonstrated comparable clinical activity and safety to the corresponding IV daratumumab regimens, with lower rates of IRR and shorter durations of adminis- tration.41 Although the dose of DARA SC on day 1 of cycle 1 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 IRR with administration beyond the
first day of cycle 1 is very low or absent.
Taken together, these findings show that DARA SC is
well tolerated, with a low rate of IRR and a shortened administration time. No new safety concerns were identi- fied, and the overall adverse event profile with SC adminis- tration was comparable to that reported with IV adminis- tration of daratumumab at the approved dose level (16 mg/kg).16,35 DARA SC achieved maximum Ctrough values that were similar to or greater than the maximum Ctrough observed for the approved 16 mg/kg IV dose following the same dosing schedule. DARA SC demonstrated robust clin- ical efficacy, producing deep and durable responses with a rapid onset. Collectively, these data indicate that, compared to the current IV formulation, DARA SC reduces adminis- tration time as well as IRR rates without compromising safety or efficacy. Based on these results, ongoing studies are actively investigating DARA SC in MM and other dis- ease states.
Disclosures
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 fund- ing 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 fund- ing from Amgen, Array BioPharma, Celgene, Janssen, Millennium, Takeda, Novartis, and Pharmacyclics. HN has no conflicts of interest to report.
Contributions
All authors developed the manuscript, provided final submission approval, and confirmed that the protocol was followed and that the data were accurate and complete.
Acknowledgments
This study was sponsored by Janssen Research & Development, LLC. The authors would like to thank the patients who participat- ed in this study and their families, as well as the study co-investi- gators, 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.
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.
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