{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T11:37:16Z","timestamp":1787312236002,"version":"build-2736575974"},"reference-count":27,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2023,3,7]],"date-time":"2023-03-07T00:00:00Z","timestamp":1678147200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J Hematol"],"published-print":{"date-parts":[[2023,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Preclinical studies have shown augmented activity when combining Bruton tyrosine kinase inhibitors (BTKi) with inhibitors of mammalian target of rapamycin (mTOR) and immunomodulatory agents (IMiD). We conducted a phase 1, open\u2010label study at five centers in USA to evaluate the safety of triplet BTKi\/mTOR\/IMiD therapy. Eligible patients were adults aged 18\u2009years or older with relapsed\/refractory CLL, B cell NHL, or Hodgkin lymphoma. Our dose escalation study used an accelerated titration design and moved sequentially from single agent BTKi (DTRMWXHS\u201012), doublet (DTRMWXHS\u201012\u2009+\u2009everolimus), and then to triplet therapy (DTRMWXHS\u201012\u2009+\u2009everolimus\u2009+\u2009pomalidomide). All drugs were dosed once daily on days 1\u201321 of each 28\u2010day\u2009cycle. The primary goal was to establish the recommended phase 2 dose of the triplet combination. Between September 27, 2016, and July 24, 2019, a total of 32 patients with a median age of 70\u2009years (range 46 to 94\u2009years) were enrolled. No MTD was identified for monotherapy and the doublet combination. The MTD for the triplet combination was determined to be DTRMWXHS\u201012 200\u2009mg\u2009+\u2009everolimus 5\u00a0mg\u2009+\u2009pomalidomide 2\u00a0mg. Responses across all studied cohorts were seen in 13 of 32 (41.9%). Combining DTRMWXHS\u201012 with everolimus and pomalidomide is tolerable and shows clinical activity. Additional trials could confirm benefit of this all\u2010oral combination therapy for relapsed\/refractory lymphomas.<\/jats:p>","DOI":"10.1002\/ajh.26888","type":"journal-article","created":{"date-parts":[[2023,2,22]],"date-time":"2023-02-22T01:53:32Z","timestamp":1677030812000},"page":"739-749","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["<scp>DTRMWXHS<\/scp>\n                    \u201012, a novel Bruton tyrosine kinase inhibitor, in combination with everolimus and pomalidomide in patients with relapsed\/refractory lymphomas: An open\u2010label, multicenter, phase 1a\/1b study"],"prefix":"10.1002","volume":"98","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7071-6475","authenticated-orcid":false,"given":"Scott F.","family":"Huntington","sequence":"first","affiliation":[{"name":"Section of Hematology Yale University  New Haven Connecticut 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US Patent 9 717 745 granted on August 1 2017 with the priority date of March 19 2015."},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1900574"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2020008727"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3026(21)00307-0"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.21.00807"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.2071"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.31044"},{"key":"e_1_2_8_21_1","volume-title":"Everolimus [package insert]","author":"Novartis","year":"2022"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2010.226"},{"key":"e_1_2_8_23_1","volume-title":"Pomalidamide [package insert]","author":"Bristol\u2010Myers Squibb","year":"2022"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdq626"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djp079"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/89.15.1138"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2013.54.8800"},{"key":"e_1_2_8_28_1","first-page":"5446","article-title":"Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute\u2013Working Group 1996 guidelines","volume":"111","author":"Hallek M","year":"2008","journal-title":"Blood J Am Soc Hematol"}],"container-title":["American Journal of Hematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajh.26888","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ajh.26888","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajh.26888","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,29]],"date-time":"2024-01-29T08:17:13Z","timestamp":1706516233000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajh.26888"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,7]]},"references-count":27,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2023,5]]}},"alternative-id":["10.1002\/ajh.26888"],"URL":"https:\/\/doi.org\/10.1002\/ajh.26888","archive":["Portico"],"relation":{},"ISSN":["0361-8609","1096-8652"],"issn-type":[{"value":"0361-8609","type":"print"},{"value":"1096-8652","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,7]]},"assertion":[{"value":"2022-12-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-02-14","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-03-07","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}