PMID- 30395359 OWN - NLM STAT- MEDLINE DCOM- 20190911 LR - 20211204 IS - 1097-0142 (Electronic) IS - 0008-543X (Print) IS - 0008-543X (Linking) VI - 124 IP - 22 DP - 2018 Nov 15 TI - Results of an early access treatment protocol of daratumumab in United States patients with relapsed or refractory multiple myeloma. PG - 4342-4349 LID - 10.1002/cncr.31706 [doi] AB - BACKGROUND: Daratumumab is a human CD38-directed monoclonal antibody indicated for the treatment of relapsed and refractory multiple myeloma (MM). METHODS: A multicenter, open-label treatment protocol provided early access to daratumumab for patients who had progressive MM after they received >/=3 prior lines of therapy that included a proteasome inhibitor and an immunomodulatory agent or if they were refractory to both a proteasome inhibitor and an immunomodulatory agent. Patients received daratumumab 16 mg/kg weekly for 8 weeks, every other week for 16 weeks, and monthly until they developed disease progression, unacceptable toxicity, or 60 days after the drug gained US approval. Treatment-emergent grade >/=3 adverse events (AEs), serious AEs, and AEs of special interest were collected. RESULTS: Three hundred forty-eight patients were enrolled at 39 US sites between June and December 2015. Patients received study therapy for a median of 1.9 months (range, 0.03-6.0 months). Fifty-two percent of patients transitioned to commercially-available daratumumab and 37% discontinued because of progressive disease. Grade >/=3 AEs occurred in 50% of patients, including thrombocytopenia (15%) and anemia (14%). Serious AEs occurred in 35% of patients (12% were drug-related), including infections (11%). Infusion reactions occurred in 56%, 2%, and 2% of patients during the first, second, and all subsequent infusions, respectively; respiratory symptoms (cough, dyspnea, throat irritation, nasal congestion) were common. The infusion reaction rate for the first infusion was 38% in 50 patients at 2 sites who received montelukast as premedication for their first infusion and 59% in patients who did not receive montelukast. CONCLUSIONS: The current findings are consistent with previously reported trials and confirm the safety profile of daratumumab in heavily pretreated US patients who have relapsed or refractory MM. Cancer 2018;124:000-000. CI - (c) 2018 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. FAU - Chari, Ajai AU - Chari A AD - Icahn School of Medicine at Mount Sinai, New York, New York. FAU - Lonial, Sagar AU - Lonial S AD - Department of Hematology and Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia. FAU - Mark, Tomer M AU - Mark TM AD - Weill Cornell Medical College, New York, New York. FAU - Krishnan, Amrita Y AU - Krishnan AY AD - Department of Hematology and Hematopoietic Cell Transplantation and Judy and Bernard Briskin Center for Multiple Myeloma, City of Hope National Medical Center, Duarte, California. FAU - Stockerl-Goldstein, Keith E AU - Stockerl-Goldstein KE AD - Division of Medical Oncology - Bone Marrow Transplantation and Leukemia Section, Washington University, St. Louis, Missouri. FAU - Usmani, Saad Z AU - Usmani SZ AD - Levine Cancer Institute, Charlotte, North Carolina. FAU - Londhe, Anil AU - Londhe A AD - Janssen Research & Development, LLC, Titusville, New Jersey. FAU - Etheredge, Delores AU - Etheredge D AD - Janssen Research & Development, LLC, Titusville, New Jersey. FAU - Fleming, Sarah AU - Fleming S AD - Janssen Research & Development, LLC, Titusville, New Jersey. FAU - Liu, Baolian AU - Liu B AD - Janssen Research & Development, LLC, Spring House, Pennsylvania. FAU - Ukropec, Jon AU - Ukropec J AD - Janssen Scientific Affairs, LLC, Horsham, Pennsylvania. FAU - Lin, Thomas S AU - Lin TS AD - Janssen Scientific Affairs, LLC, Horsham, Pennsylvania. FAU - Jagannath, Sundar AU - Jagannath S AD - Icahn School of Medicine at Mount Sinai, New York, New York. FAU - Nooka, Ajay K AU - Nooka AK AD - Department of Hematology and Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia. LA - eng GR - Janssen Research & Development/International PT - Clinical Trial PT - Journal Article PT - Multicenter Study PT - Research Support, Non-U.S. Gov't DEP - 20181105 PL - United States TA - Cancer JT - Cancer JID - 0374236 RN - 0 (Acetates) RN - 0 (Antibodies, Monoclonal) RN - 0 (Antineoplastic Agents, Immunological) RN - 0 (Cyclopropanes) RN - 0 (Quinolines) RN - 0 (Sulfides) RN - 4Z63YK6E0E (daratumumab) RN - MHM278SD3E (montelukast) SB - IM MH - Acetates/administration & dosage MH - Adult MH - Aged MH - Aged, 80 and over MH - Antibodies, Monoclonal/*administration & dosage/adverse effects MH - Antineoplastic Agents, Immunological/*administration & dosage/adverse effects MH - Cyclopropanes MH - Drug Administration Schedule MH - Drug Approval MH - Female MH - Humans MH - Infusions, Intravenous MH - Injection Site Reaction/prevention & control MH - Male MH - Middle Aged MH - Multiple Myeloma/*drug therapy MH - Neoplasm Recurrence, Local/*drug therapy MH - Quinolines/administration & dosage MH - Sulfides MH - Survival Analysis MH - Treatment Outcome MH - United States PMC - PMC6587745 OTO - NOTNLM OT - CD38 OT - daratumumab OT - monoclonal antibodies OT - montelukast OT - multiple myeloma COIS- Ajai Chari reports personal fees research funding, and membership on an advisory board from Amgen, Celgene, Janssen, Novartis, and Takeda; personal fees from Bristol Myers Squibb and The Binding Site outside the submitted work; research funding from Array Biopharma and Pharmacyclics outside the submitted work; and membership on an advisory board for Seattle Genetics and Adaptive Biotechnology outside the submitted work. Sagar Lonial reports personal fees from Amgen, Bristol-Myers Squibb, Celgene, Janssen, Merck, Millennium, Novartis, and Onyx outside the submitted work. Tomer M. Mark reports research funding from Amgen and Celgene and membership on a board of directors or an advisory committee for Celgene, Janssen, and Takeda, all outside the submitted work. Amrita Y. Krishnan reports personal fees from Celgene, Onyx, Janssen, and Takeda outside the submitted work; serves on a scientific advisory board for Sutro; and owns stock in Celgene. Keith E. Stockerl-Goldstein reports personal fees from Janssen outside the submitted work. Saad Z. Usmani reports research funding from Amgen, Array, BioPharma, Bristol-Myers Squibb, Celgene, Janssen, Merck, Millennium, Novartis, Onyx, Pharmacyclics, Sanofi, Skyline, and Takeda; personal fees from Amgen, BioPharma, Bristol-Myers Squibb, Celgene, Janssen, Merck, Millennium, Novartis, Onyx, Sanofi, Skyline, and Takeda; and serves on a board of directors or advisory committee for BioPharma, Celgene, Janssen, Millennium, Onyx, Sanofi, Skyline, and Takeda, all during the conduct of the study. Jon Ukropec and Thomas S. Lin are employees of Janssen Scientific Affairs, LLC. Anil Londhe, Delores Etheredge, Sarah Fleming, and Baolian Liu are employees of Janssen Research & Development, LLC. Ajay K. Nooka reports personal fees from Janssen Pharmaceuticals during the conduct of the study and from Novartis, Onyx, Spectrum, Celgene, and Adaptive Technologies and serving on an advisory board for Adaptive technologies, Amgen, BMS Pharmaceuticals, Celgene, GSK, Novartis, Spectrum, and Takeda. outside the submitted work. Sundar Jagannath reports personal fees from Celgene, Bristol-Myers Squibb, Novartis, Janssen, and Merck outside the submitted work. EDAT- 2018/11/06 06:00 MHDA- 2019/09/12 06:00 PMCR- 2019/06/21 CRDT- 2018/11/06 06:00 PHST- 2018/01/26 00:00 [received] PHST- 2018/05/02 00:00 [revised] PHST- 2018/07/09 00:00 [accepted] PHST- 2018/11/06 06:00 [pubmed] PHST- 2019/09/12 06:00 [medline] PHST- 2018/11/06 06:00 [entrez] PHST- 2019/06/21 00:00 [pmc-release] AID - CNCR31706 [pii] AID - 10.1002/cncr.31706 [doi] PST - ppublish SO - Cancer. 2018 Nov 15;124(22):4342-4349. doi: 10.1002/cncr.31706. Epub 2018 Nov 5.