{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:48:40Z","timestamp":1790642920136,"version":"4.1.0"},"reference-count":21,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2021,2,27]],"date-time":"2021-02-27T00:00:00Z","timestamp":1614384000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2021,2,27]],"date-time":"2021-02-27T00:00:00Z","timestamp":1614384000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"}],"funder":[{"DOI":"10.13039\/100008272","name":"Novartis Pharmaceuticals Corporation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008272","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Int J Hematol"],"published-print":{"date-parts":[[2021,6]]},"DOI":"10.1007\/s12185-021-03096-9","type":"journal-article","created":{"date-parts":[[2021,2,27]],"date-time":"2021-02-27T02:02:41Z","timestamp":1614391361000},"page":"797-806","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["A phase I, dose-escalation study of oral PIM447 in Japanese patients with relapsed and\/or refractory multiple myeloma"],"prefix":"10.1007","volume":"113","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4951-960X","authenticated-orcid":false,"given":"Shinsuke","family":"Iida","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazutaka","family":"Sunami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hironobu","family":"Minami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiyohiko","family":"Hatake","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Risa","family":"Sekiguchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuto","family":"Natsume","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norifumi","family":"Ishikawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikael","family":"Rinne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masafumi","family":"Taniwaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,2,27]]},"reference":[{"key":"3096_CR1","doi-asserted-by":"publisher","first-page":"2197","DOI":"10.1016\/S0140-6736(14)60493-1","volume":"385","author":"C Rollig","year":"2015","unstructured":"Rollig C, Knop S, Bornhauser M. Multiple myeloma. Lancet. 2015;385:2197\u2013208.","journal-title":"Lancet"},{"key":"3096_CR2","doi-asserted-by":"publisher","first-page":"529","DOI":"10.1007\/s40262-017-0598-1","volume":"57","author":"X Yan","year":"2018","unstructured":"Yan X, Clemens PL, Puchalski T, Lonial S, Lokhorst H, Voorhees PM, et al. Influence of disease and patient characteristics on daratumumab exposure and clinical outcomes in relapsed or refractory multiple myeloma. Clin Pharmacokinet. 2018;57:529\u201338.","journal-title":"Clin Pharmacokinet"},{"key":"3096_CR3","doi-asserted-by":"publisher","first-page":"2692","DOI":"10.1080\/10428194.2018.1448084","volume":"59","author":"L Gengenbach","year":"2018","unstructured":"Gengenbach L, Reinhardt H, Ihorst G, Ajayi S, Dold SM, Kohler M, et al. Navigating the changing multiple myeloma treatment landscape: clinical practice patterns of MM patients treated in- and outside German DSMM study group trials. Leuk Lymphoma. 2018;59:2692\u20139.","journal-title":"Leuk Lymphoma"},{"key":"3096_CR4","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1158\/1078-0432.CCR-16-0230","volume":"23","author":"T Paino","year":"2017","unstructured":"Paino T, Garcia-Gomez A, Gonzalez-Mendez L, San-Segundo L, Hernandez-Garcia S, Lopez-Iglesias AA, et al. The novel pan-PIM kinase inhibitor, PIM447, displays dual antimyeloma and bone-protective effects, and potently synergizes with current standards of care. Clin Cancer Res. 2017;23:225\u201338.","journal-title":"Clin Cancer Res"},{"key":"3096_CR5","doi-asserted-by":"publisher","first-page":"1004","DOI":"10.3324\/haematol.2009.017079","volume":"95","author":"L Brault","year":"2010","unstructured":"Brault L, Gasser C, Bracher F, Huber K, Knapp S, Schwaller J. PIM serine\/threonine kinases in the pathogenesis and therapy of hematologic malignancies and solid cancers. Haematologica. 2010;95:1004\u201315.","journal-title":"Haematologica"},{"key":"3096_CR6","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1038\/nrc2986","volume":"11","author":"MC Nawijn","year":"2011","unstructured":"Nawijn MC, Alendar A, Berns A. For better or for worse: the role of Pim oncogenes in tumorigenesis. Nat Rev Cancer. 2011;11:23\u201334.","journal-title":"Nat Rev Cancer"},{"key":"3096_CR7","doi-asserted-by":"publisher","first-page":"1182","DOI":"10.1038\/leu.2011.60","volume":"25","author":"J Asano","year":"2011","unstructured":"Asano J, Nakano A, Oda A, Amou H, Hiasa M, Takeuchi K, et al. The serine\/threonine kinase Pim-2 is a novel anti-apoptotic mediator in myeloma cells. Leukemia. 2011;25:1182\u20138.","journal-title":"Leukemia"},{"key":"3096_CR8","doi-asserted-by":"publisher","first-page":"e325","DOI":"10.1038\/bcj.2015.46","volume":"5","author":"NA Keane","year":"2015","unstructured":"Keane NA, Reidy M, Natoni A, Raab MS, O\u2019Dwyer M. Targeting the Pim kinases in multiple myeloma. Blood Cancer J. 2015;5:e325.","journal-title":"Blood Cancer J"},{"key":"3096_CR9","doi-asserted-by":"publisher","first-page":"e462","DOI":"10.1038\/bcj.2016.73","volume":"6","author":"J Ramachandran","year":"2016","unstructured":"Ramachandran J, Santo L, Siu KT, Panaroni C, Raje N. Pim2 is important for regulating DNA damage response in multiple myeloma cells. Blood Cancer J. 2016;6:e462.","journal-title":"Blood Cancer J"},{"key":"3096_CR10","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1038\/leu.2014.147","volume":"29","author":"M Hiasa","year":"2015","unstructured":"Hiasa M, Teramachi J, Oda A, Amachi R, Harada T, Nakamura S, et al. Pim-2 kinase is an important target of treatment for tumor progression and bone loss in myeloma. Leukemia. 2015;29:207\u201317.","journal-title":"Leukemia"},{"issue":"21","key":"3096_CR11","doi-asserted-by":"publisher","first-page":"1666","DOI":"10.1182\/blood.V122.21.1666.1666","volume":"122","author":"PD Garcia","year":"2013","unstructured":"Garcia PD, Langowski JL, Holash J, Burger M, Zang R, Zavorotinskaya T, et al. The pan-PIM kinase inhibitor LGH447 shows activity in PIM2-dependent multiple myeloma and in AML models. Blood. 2013;122(21):1666 ((Abstract 1666)).","journal-title":"Blood"},{"key":"3096_CR12","doi-asserted-by":"publisher","first-page":"1715","DOI":"10.1038\/leu.2016.379","volume":"31","author":"JR Nair","year":"2017","unstructured":"Nair JR, Caserta J, Belko K, Howell T, Fetterly G, Baldino C, et al. Novel inhibition of PIM2 kinase has significant anti-tumor efficacy in multiple myeloma. Leukemia. 2017;31:1715\u201326.","journal-title":"Leukemia"},{"key":"3096_CR13","doi-asserted-by":"publisher","first-page":"2924","DOI":"10.1038\/s41375-019-0482-0","volume":"33","author":"MS Raab","year":"2019","unstructured":"Raab MS, Thomas SK, Ocio EM, Guenther A, Goh YT, Talpaz M, et al. The first-in-human study of the pan-PIM kinase inhibitor PIM447 in patients with relapsed and\/or refractory multiple myeloma. Leukemia. 2019;33:2924\u201333.","journal-title":"Leukemia"},{"key":"3096_CR14","doi-asserted-by":"publisher","first-page":"1103","DOI":"10.1002\/(SICI)1097-0258(19980530)17:10<1103::AID-SIM793>3.0.CO;2-9","volume":"17","author":"J Babb","year":"1998","unstructured":"Babb J, Rogatko A, Zacks S. Cancer phase I clinical trials: efficient dose escalation with overdose control. Stat Med. 1998;17:1103\u201320.","journal-title":"Stat Med"},{"key":"3096_CR15","doi-asserted-by":"publisher","first-page":"2420","DOI":"10.1002\/sim.3230","volume":"27","author":"B Neuenschwander","year":"2008","unstructured":"Neuenschwander B, Branson M, Gsponer T. Critical aspects of the Bayesian approach to phase I cancer trials. Stat Med. 2008;27:2420\u201339.","journal-title":"Stat Med"},{"key":"3096_CR16","doi-asserted-by":"publisher","first-page":"1467","DOI":"10.1038\/sj.leu.2404284","volume":"20","author":"BG Durie","year":"2006","unstructured":"Durie BG, Harousseau JL, Miguel JS, Blade J, Barlogie B, Anderson K, et al. International uniform response criteria for multiple myeloma. Leukemia. 2006;20:1467\u201373.","journal-title":"Leukemia"},{"issue":"21","key":"3096_CR17","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1182\/blood.V124.21.301.301","volume":"124","author":"MS Raab","year":"2014","unstructured":"Raab MS, Ocio EM, Thomas SK, G\u00fcnther A, Goh YT, Lebovic D, et al. Phase 1 study update of the novel pan-PIM kinase inhibitor LGH447 in patients with relapsed\/refractory multiple myeloma. Blood. 2014;124(21):301 ((Abstract 301)).","journal-title":"Blood"},{"key":"3096_CR18","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1186\/1756-8722-6-12","volume":"6","author":"N An","year":"2013","unstructured":"An N, Kraft AS, Kang Y. Abnormal hematopoietic phenotypes in Pim kinase triple knockout mice. J Hematol Oncol. 2013;6:12.","journal-title":"J Hematol Oncol"},{"key":"3096_CR19","doi-asserted-by":"publisher","first-page":"1834","DOI":"10.1158\/1078-0432.CCR-13-2062","volume":"20","author":"PD Garcia","year":"2014","unstructured":"Garcia PD, Langowski JL, Wang Y, Chen M, Castillo J, Fanton C, et al. Pan-PIM kinase inhibition provides a novel therapy for treating hematologic cancers. Clin Cancer Res. 2014;20:1834\u201345.","journal-title":"Clin Cancer Res"},{"key":"3096_CR20","doi-asserted-by":"publisher","first-page":"1610","DOI":"10.1182\/blood-2013-01-481457","volume":"122","author":"J Lu","year":"2013","unstructured":"Lu J, Zavorotinskaya T, Dai Y, Niu XH, Castillo J, Sim J, et al. Pim2 is required for maintaining multiple myeloma cell growth through modulating TSC2 phosphorylation. Blood. 2013;122:1610\u201320.","journal-title":"Blood"},{"key":"3096_CR21","unstructured":"Pa\u00edno T, San-Segundo L, Hern\u00e1ndez-Garc\u00eda S, Gonz\u00e1lez-M\u00e9ndez L, Algarin EM, Mart\u00edn-S\u00e1nchez M et al. The pan-PIM kinase inhibitor, PIM447, potentially synergizes with pomalidomide plus dexamethasone in preclinical in vitro and in vivo models of multiple myeloma. EHA Library. 2017;(180998):E1222. (Abstract E1222)."}],"container-title":["International Journal of Hematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12185-021-03096-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12185-021-03096-9\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12185-021-03096-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,5,20]],"date-time":"2021-05-20T16:20:20Z","timestamp":1621527620000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12185-021-03096-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,27]]},"references-count":21,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2021,6]]}},"alternative-id":["3096"],"URL":"https:\/\/doi.org\/10.1007\/s12185-021-03096-9","relation":{},"ISSN":["0925-5710","1865-3774"],"issn-type":[{"value":"0925-5710","type":"print"},{"value":"1865-3774","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,27]]},"assertion":[{"value":"3 September 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 January 2021","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 January 2021","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 February 2021","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}]}}