{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T23:59:43Z","timestamp":1792627183106,"version":"4.5.0"},"reference-count":12,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2023,9,18]],"date-time":"2023-09-18T00:00:00Z","timestamp":1694995200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,9,18]],"date-time":"2023-09-18T00:00:00Z","timestamp":1694995200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Invest New Drugs"],"published-print":{"date-parts":[[2023,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The intravenous administration (IV) of daratumumab sometimes causes an infusion reaction and needs a long infusion time. Recently, a subcutaneous formulation (SC) of daratumumab, which has fewer infusion reactions and shorter administration time, was approved. However, because SC has a fixed dose, overdosing is a concern for patients with low body weights. In this study, we investigated the safety and blood levels of daratumumab after switching from IV to SC in patients with multiple myeloma (MM). Patients who switched from IV to SC of daratumumab between June 2021 and May 2022 at Kobe City Medical Center General Hospital were included in the study. Blood daratumumab levels were measured using liquid chromatography-tandem mass spectrometry. Safety after switching from IV to SC was evaluated for six months and graded according to the Common Terminology Criteria for Adverse Events, version 5.0. The median body weight of ten patients included in the analysis was 57.4\u00a0kg (range: 45.0\u201374.4). Blood daratumumab levels were significantly increased after switching to SC (p\u2009=\u20090.002); median through concentration at the last IV dose was 403.6\u00a0\u03bcg\/mL (range: 96.3\u2013776.3) and that at the third SC dose was 557.1\u00a0\u03bcg\/mL (range: 288.3\u2013997.2). Grade 1\u20132 injection site reactions were observed in six patients (60.0%) after switching to SC. A new grade 3 adverse event was observed in only one patient (neutropenia). The blood levels of daratumumab were significantly increased after switching from IV to SC in patients with MM; however, the dosage was tolerable.<\/jats:p>","DOI":"10.1007\/s10637-023-01392-1","type":"journal-article","created":{"date-parts":[[2023,9,18]],"date-time":"2023-09-18T06:01:57Z","timestamp":1695016917000},"page":"761-767","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Safety and blood levels of daratumumab after switching from intravenous to subcutaneous administration in patients with multiple myeloma"],"prefix":"10.1007","volume":"41","author":[{"given":"Kenta","family":"Yamaoka","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0820-1208","authenticated-orcid":false,"given":"Kei","family":"Irie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuhiro","family":"Hiramoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaki","family":"Hirabatake","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8499-131X","authenticated-orcid":false,"given":"Hiroaki","family":"Ikesue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5702-5124","authenticated-orcid":false,"given":"Tohru","family":"Hashida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5563-6730","authenticated-orcid":false,"given":"Tadashi","family":"Shimizu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2098-9616","authenticated-orcid":false,"given":"Takayuki","family":"Ishikawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuyuki","family":"Muroi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,9,18]]},"reference":[{"issue":"5","key":"1392_CR1","doi-asserted-by":"publisher","first-page":"1122","DOI":"10.1038\/leu.2013.313","volume":"28","author":"SK Kumar","year":"2014","unstructured":"Kumar SK, Dispenzieri A, Lacy MQ, Gertz MA, Buadi FK, Pandey S et al (2014) Continued improvement in survival in multiple myeloma: changes in early mortality and outcomes in older patients. Leukemia 28(5):1122\u20131128. https:\/\/doi.org\/10.1038\/leu.2013.313","journal-title":"Leukemia"},{"issue":"8","key":"1392_CR2","doi-asserted-by":"publisher","first-page":"754","DOI":"10.1056\/NEJMoa1606038","volume":"375","author":"A Palumbo","year":"2016","unstructured":"Palumbo A, Chanan-Khan A, Weisel K, Nooka AK, Masszi T, Beksac M et al (2016) Daratumumab, bortezomib, and dexamethasone for multiple myeloma. N Engl J Med 375(8):754\u2013766. https:\/\/doi.org\/10.1056\/NEJMoa1606038","journal-title":"N Engl J Med"},{"issue":"11","key":"1392_CR3","doi-asserted-by":"publisher","first-page":"1582","DOI":"10.1016\/S1470-2045(21)00466-6","volume":"22","author":"T Facon","year":"2021","unstructured":"Facon T, Kumar SK, Plesner T, Orlowski RZ, Moreau P, Bahlis N et al (2021) Daratumumab, lenalidomide, and dexamethasone versus lenalidomide and dexamethasone alone in newly diagnosed multiple myeloma (Maia): overall survival results from a randomised, open-label, phase 3 trial. Lancet Oncol 22(11):1582\u20131596. https:\/\/doi.org\/10.1016\/S1470-2045(21)00466-6","journal-title":"Lancet Oncol"},{"issue":"11","key":"1392_CR4","doi-asserted-by":"publisher","first-page":"1347","DOI":"10.1634\/theoncologist.2017-0229","volume":"22","author":"V Bhatnagar","year":"2017","unstructured":"Bhatnagar V, Gormley NJ, Luo L, Shen YL, Sridhara R, Subramaniam S et al (2017) FDA approval summary: daratumumab for treatment of multiple myeloma after one prior therapy. Oncologist 22(11):1347\u20131353. https:\/\/doi.org\/10.1634\/theoncologist.2017-0229","journal-title":"Oncologist"},{"issue":"10245","key":"1392_CR5","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1016\/S0140-6736(20)30734-0","volume":"396","author":"M Dimopoulos","year":"2020","unstructured":"Dimopoulos M, Quach H, Mateos MV, Landgren O, Leleu X, Siegel D et al (2020) Carfilzomib, dexamethasone, and daratumumab versus carfilzomib and dexamethasone for patients with relapsed or refractory multiple myeloma (CANDOR): results from a randomised, multicentre, open-label, phase 3 study. Lancet 396(10245):186\u2013197. https:\/\/doi.org\/10.1016\/S0140-6736(20)30734-0","journal-title":"Lancet"},{"key":"1392_CR6","doi-asserted-by":"publisher","first-page":"851864","DOI":"10.3389\/fonc.2022.851864","volume":"12","author":"F Bonello","year":"2022","unstructured":"Bonello F, Rocchi S, Baril\u00e0 G, Sandrone M, Talarico M, Zamagni E et al (2022) Safety of rapid daratumumab infusion: a retrospective, multicenter, real-life analysis on 134 patients with multiple myeloma. Front Oncol 12:851864. https:\/\/doi.org\/10.3389\/fonc.2022.851864","journal-title":"Front Oncol"},{"issue":"5","key":"1392_CR7","doi-asserted-by":"publisher","first-page":"e370","DOI":"10.1016\/S2352-3026(20)30070-3","volume":"7","author":"MV Mateos","year":"2020","unstructured":"Mateos MV, Nahi H, Legiec W, Grosicki S, Vorobyev V, Spicka I et al (2020) Subcutaneous versus intravenous daratumumab in patients with relapsed or refractory multiple myeloma (COLUMBA): a multicentre, open-label, non-inferiority, randomised, phase 3 trial. Lancet Haematol 7(5):e370\u2013e380. https:\/\/doi.org\/10.1016\/S2352-3026(20)30070-3","journal-title":"Lancet Haematol"},{"issue":"5","key":"1392_CR8","doi-asserted-by":"publisher","first-page":"869","DOI":"10.1111\/bjh.16980","volume":"192","author":"A Chari","year":"2021","unstructured":"Chari A, Rodriguez-Otero P, McCarthy H, Suzuki K, Hungria V, Sureda Balari A et al (2021) 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 192(5):869\u2013878. https:\/\/doi.org\/10.1111\/bjh.16980","journal-title":"Br J Haematol"},{"issue":"6","key":"1392_CR9","doi-asserted-by":"publisher","first-page":"716","DOI":"10.1097\/FTD.0000000000000558","volume":"40","author":"K Irie","year":"2018","unstructured":"Irie K, Okada A, Yamasaki Y, Kokan C, Hata A, Kaji R et al (2018) An LC-MS\/MS method for absolute quantification of nivolumab in human plasma: application to clinical therapeutic drug monitoring. Ther Drug Monit 40(6):716\u2013724. https:\/\/doi.org\/10.1097\/FTD.0000000000000558","journal-title":"Ther Drug Monit"},{"key":"1392_CR10","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.15628","author":"AG Dosne","year":"2022","unstructured":"Dosne AG, Li X, Luo MM, Nnane I, Dimopoulos MA, Terpos E et al (2022) Population pharmacokinetics and exposure-response analyses of daratumumab plus pomalidomide\/dexamethasone in relapsed or refractory multiple myeloma. Br J Clin Pharmacol. https:\/\/doi.org\/10.1111\/bcp.15628","journal-title":"Br J Clin Pharmacol"},{"issue":"8","key":"1392_CR11","doi-asserted-by":"publisher","first-page":"668","DOI":"10.1182\/blood.2019000667","volume":"134","author":"SZ Usmani","year":"2019","unstructured":"Usmani SZ, Nahi H, Mateos MV, van de Donk NWCJ, Chari A, Kaufman JL et al (2019) Subcutaneous delivery of daratumumab in relapsed or refractory multiple myeloma. Blood 134(8):668\u2013677. https:\/\/doi.org\/10.1182\/blood.2019000667","journal-title":"Blood"},{"key":"1392_CR12","doi-asserted-by":"publisher","unstructured":"Mateos MV, Rigaudeau S, Basu S, Spicka I, Schots R, Wrobel T et al (2022) Switching to daratumumab SC from IV is safe and preferred by patients with multiple myeloma. J Oncol Pharm Pract 10781552221103551. https:\/\/doi.org\/10.1177\/10781552221103551","DOI":"10.1177\/10781552221103551"}],"container-title":["Investigational New Drugs"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10637-023-01392-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10637-023-01392-1\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10637-023-01392-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,7]],"date-time":"2023-10-07T07:04:38Z","timestamp":1696662278000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10637-023-01392-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,18]]},"references-count":12,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2023,10]]}},"alternative-id":["1392"],"URL":"https:\/\/doi.org\/10.1007\/s10637-023-01392-1","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-3229878\/v1","asserted-by":"object"}]},"ISSN":["0167-6997","1573-0646"],"issn-type":[{"value":"0167-6997","type":"print"},{"value":"1573-0646","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,18]]},"assertion":[{"value":"3 August 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 September 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 September 2023","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"The study was conducted in accordance with the principles of the Declaration of Helsinki. The study protocol was approved by the Ethics Committee of Kobe City Medical Center General Hospital (approval number: zn210615).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"Informed consent was obtained from all patients using a consent explanation document approved by the Ethics Committee of Kobe City Medical Center General Hospital.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"Not applicable.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}}]}}