{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T18:32:34Z","timestamp":1761849154201,"version":"build-2065373602"},"reference-count":18,"publisher":"Springer Science and Business Media LLC","issue":"11","license":[{"start":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T00:00:00Z","timestamp":1756771200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T00:00:00Z","timestamp":1756771200000},"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":["Int J Clin Oncol"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Patients with relapsed\/refractory (R\/R) mantle cell lymphoma (MCL) face a poor prognosis in the absence of effective treatment options. Ibrutinib plus venetoclax demonstrated high response rates and a tolerable safety profile in the primary analysis of the Phase 2, M20-075 study (NCT04477486) in Japanese patients with R\/R MCL. We report updated efficacy and safety from this study with longer follow-up.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Patients received 560\u00a0mg ibrutinib and 400\u00a0mg venetoclax (5-week ramp-up to 400\u00a0mg) once daily for up to 104\u00a0weeks followed by ibrutinib monotherapy. Primary endpoint was Independent Review Committee-assessed complete response (CR) rate. Secondary endpoints included overall response rate (ORR), duration of response (DOR), undetectable minimal residual disease (uMRD) in patients achieving CR, progression-free survival (PFS), overall survival (OS), and safety.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>After a median follow-up of 37.2\u00a0months, 13 patients had received ibrutinib plus venetoclax, 8 (62%) remained on ibrutinib monotherapy, and 9 (69%) completed 24\u00a0months of venetoclax. ORR was 83% (10\/12 [per-protocol population]; all CR); median DOR was not reached. All 6 patients positive for MRD at baseline who achieved CR had uMRD. Median PFS and OS were not reached. Most frequent Grade\u2009\u2265\u20093 treatment-emergent adverse events (TEAEs) were neutropenia (46%) and leukopenia (23%); one TEAE leading to treatment discontinuation was squamous cell carcinoma unrelated to treatment. There were no cases of tumor lysis syndrome or TEAEs leading to death.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Long-term follow-up of ibrutinib plus venetoclax showed prolonged efficacy and a well-tolerated safety profile in Japanese patients with R\/R MCL.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s10147-025-02865-4","type":"journal-article","created":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T16:57:44Z","timestamp":1756832264000},"page":"2352-2361","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Long-term outcomes of venetoclax and ibrutinib in Japanese patients with relapsed\/refractory mantle cell lymphoma"],"prefix":"10.1007","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8361-9973","authenticated-orcid":false,"given":"Hideki","family":"Goto","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Satoshi","family":"Ito","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masahiro","family":"Kizaki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masaki","family":"Yamaguchi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noriko","family":"Fukuhara","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Koji","family":"Kato","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toko","family":"Saito","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasuhito","family":"Terui","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomomi","family":"Soshin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natsuko","family":"Satomi-Tsushita","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hideyuki","family":"Honda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chen","family":"Qian","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Koji","family":"Izutsu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,9,2]]},"reference":[{"issue":"3","key":"2865_CR1","doi-asserted-by":"publisher","first-page":"135","DOI":"10.3960\/jslrt.20056","volume":"61","author":"K Izutsu","year":"2021","unstructured":"Izutsu K, Suzumiya J, Takizawa J et al (2021) Real world treatment practices for mantle cell lymphoma in Japan: an observational database research study (CLIMBER-DBR). J Clin Exp Hematop 61(3):135\u2013144. https:\/\/doi.org\/10.3960\/jslrt.20056","journal-title":"J Clin Exp Hematop"},{"issue":"5","key":"2865_CR2","doi-asserted-by":"publisher","first-page":"666","DOI":"10.1182\/blood.2021013326","volume":"139","author":"TA Eyre","year":"2022","unstructured":"Eyre TA, Cheah CY, Wang ML (2022) Therapeutic options for relapsed\/refractory mantle cell lymphoma. Blood 139(5):666\u2013677. https:\/\/doi.org\/10.1182\/blood.2021013326","journal-title":"Blood"},{"issue":"2","key":"2865_CR3","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1007\/s10147-023-02443-6","volume":"29","author":"H Goto","year":"2024","unstructured":"Goto H, Ito S, Kizaki M et al (2024) Phase 2 study of ibrutinib plus venetoclax in Japanese patients with relapsed\/refractory mantle cell lymphoma. Int J Clin Oncol 29(2):232\u2013240. https:\/\/doi.org\/10.1007\/s10147-023-02443-6","journal-title":"Int J Clin Oncol"},{"issue":"14","key":"2865_CR4","doi-asserted-by":"publisher","first-page":"4122","DOI":"10.1182\/bloodadvances.2022007247","volume":"6","author":"M Narkhede","year":"2022","unstructured":"Narkhede M, Goyal G, Shea L et al (2022) Evaluating real-world treatment patterns and outcomes of mantle cell lymphoma. Blood Adv 6(14):4122\u20134131. https:\/\/doi.org\/10.1182\/bloodadvances.2022007247","journal-title":"Blood Adv"},{"issue":"23","key":"2865_CR5","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1182\/blood.V126.23.254.254","volume":"126","author":"JF Gerecitano","year":"2015","unstructured":"Gerecitano JF, Roberts AW, Seymour JF et al (2015) A phase 1 study of Venetoclax (ABT-199 \/ GDC-0199) monotherapy in patients with relapsed\/refractory non-Hodgkin lymphoma. Blood 126(23):254","journal-title":"Blood"},{"issue":"13","key":"2865_CR6","doi-asserted-by":"publisher","first-page":"2983","DOI":"10.1182\/bloodadvances.2022008916","volume":"7","author":"Y Sawalha","year":"2023","unstructured":"Sawalha Y, Goyal S, Switchenko JM et al (2023) A multicenter analysis of the outcomes with venetoclax in patients with relapsed mantle cell lymphoma. Blood Adv 7(13):2983\u20132993. https:\/\/doi.org\/10.1182\/bloodadvances.2022008916","journal-title":"Blood Adv"},{"issue":"2","key":"2865_CR7","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1038\/leu.2013.249","volume":"28","author":"M Axelrod","year":"2014","unstructured":"Axelrod M, Ou Z, Brett LK et al (2014) Combinatorial drug screening identifies synergistic co-targeting of Bruton\u2019s tyrosine kinase and the proteasome in mantle cell lymphoma. Leukemia 28(2):407\u2013410. https:\/\/doi.org\/10.1038\/leu.2013.249","journal-title":"Leukemia"},{"issue":"13","key":"2865_CR8","doi-asserted-by":"publisher","first-page":"1211","DOI":"10.1056\/NEJMoa1715519","volume":"378","author":"CS Tam","year":"2018","unstructured":"Tam CS, Anderson MA, Pott C et al (2018) Ibrutinib plus venetoclax for the treatment of mantle-cell lymphoma. N Engl J Med 378(13):1211\u20131223. https:\/\/doi.org\/10.1056\/NEJMoa1715519","journal-title":"N Engl J Med"},{"key":"2865_CR9","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1016\/S1470-2045(24)00682-X","volume":"26","author":"MJW Wang","year":"2025","unstructured":"Wang MJW, Trneny M, Belada D et al (2025) Ibrutinib plus venetoclax in relapsed or refractory mantle cell lymphoma (SYMPATICO): a multicentre, randomised, double-blind, placebo-controlled, phase 3 study. Lancet Oncol 26:200\u2013213","journal-title":"Lancet Oncol"},{"key":"2865_CR10","unstructured":"VENCLEXTA (venetoclax). Prescribing information. AbbVie Inc.; 2024."},{"issue":"19","key":"2865_CR11","doi-asserted-by":"publisher","first-page":"1844","DOI":"10.1056\/NEJMra0904569","volume":"364","author":"SC Howard","year":"2011","unstructured":"Howard SC, Jones DP, Pui CH (2011) The tumor lysis syndrome. N Engl J Med 364(19):1844\u20131854. https:\/\/doi.org\/10.1056\/NEJMra0904569","journal-title":"N Engl J Med"},{"issue":"12","key":"2865_CR12","doi-asserted-by":"publisher","first-page":"1785","DOI":"10.1111\/cas.13076","volume":"107","author":"D Maruyama","year":"2016","unstructured":"Maruyama D, Nagai H, Fukuhara N et al (2016) Efficacy and safety of ibrutinib in Japanese patients with relapsed or refractory mantle cell lymphoma. Cancer Sci 107(12):1785\u20131790. https:\/\/doi.org\/10.1111\/cas.13076","journal-title":"Cancer Sci"},{"issue":"8","key":"2865_CR13","doi-asserted-by":"publisher","first-page":"1799","DOI":"10.1038\/s41375-018-0023-2","volume":"32","author":"S Rule","year":"2018","unstructured":"Rule S, Jurczak W, Jerkeman M et al (2018) Ibrutinib versus temsirolimus: 3-year follow-up of patients with previously treated mantle cell lymphoma from the phase 3, international, randomized, open-label RAY study. Leukemia 32(8):1799\u20131803. https:\/\/doi.org\/10.1038\/s41375-018-0023-2","journal-title":"Leukemia"},{"issue":"2","key":"2865_CR14","doi-asserted-by":"publisher","first-page":"98","DOI":"10.3960\/jslrt.19006","volume":"59","author":"D Maruyama","year":"2019","unstructured":"Maruyama D, Nagai H, Fukuhara N et al (2019) Final analysis of a phase II study of ibrutinib in Japanese patients with relapsed\/refractory mantle cell lymphoma. J Clin Exp Hematop 59(2):98\u2013100. https:\/\/doi.org\/10.3960\/jslrt.19006","journal-title":"J Clin Exp Hematop"},{"key":"2865_CR15","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1016\/S1470-2045(24)00682-X","volume":"26","author":"M Wang","year":"2025","unstructured":"Wang M, Jurczak W, Trneny M et al (2025) Ibrutinib plus venetoclax in relapsed or refractory mantle cell lymphoma (SYMPATICO): a multicentre, randomised, double-blind, placebo-controlled, phase 3 study. Lancet Oncol 26:200\u2013213","journal-title":"Lancet Oncol"},{"issue":"4","key":"2865_CR16","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1080\/17474086.2022.2067526","volume":"15","author":"BW Christensen","year":"2022","unstructured":"Christensen BW, Zaha VG, Awan FT (2022) Cardiotoxicity of BTK inhibitors: ibrutinib and beyond. Expert Rev Hematol 15(4):321\u2013331. https:\/\/doi.org\/10.1080\/17474086.2022.2067526","journal-title":"Expert Rev Hematol"},{"key":"2865_CR17","doi-asserted-by":"publisher","first-page":"3225","DOI":"10.2147\/dddt.S377697","volume":"16","author":"R Dong","year":"2022","unstructured":"Dong R, Yan Y, Zeng X et al (2022) Ibrutinib-associated cardiotoxicity: from the pharmaceutical to the clinical. Drug Des Devel Ther 16:3225\u20133239. https:\/\/doi.org\/10.2147\/dddt.S377697","journal-title":"Drug Des Devel Ther"},{"issue":"8","key":"2865_CR18","doi-asserted-by":"publisher","first-page":"867","DOI":"10.1182\/blood.2023023388","volume":"144","author":"SM Handunnetti","year":"2024","unstructured":"Handunnetti SM, Anderson MA, Burbury K et al (2024) Seven-year outcomes of venetoclax-ibrutinib therapy in mantle cell lymphoma: durable responses and treatment-free remissions. Blood 144(8):867\u2013872. https:\/\/doi.org\/10.1182\/blood.2023023388","journal-title":"Blood"}],"container-title":["International Journal of Clinical Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10147-025-02865-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10147-025-02865-4\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10147-025-02865-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T18:11:54Z","timestamp":1761847914000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10147-025-02865-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,2]]},"references-count":18,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2025,11]]}},"alternative-id":["2865"],"URL":"https:\/\/doi.org\/10.1007\/s10147-025-02865-4","relation":{},"ISSN":["1341-9625","1437-7772"],"issn-type":[{"type":"print","value":"1341-9625"},{"type":"electronic","value":"1437-7772"}],"subject":[],"published":{"date-parts":[[2025,9,2]]},"assertion":[{"value":"3 April 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 August 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 September 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"H. Goto reports lecture fees earned from Kyowa Kirin, Vie, Chugai, Novartis, Bristol Myers Squibb, Gilead and research funding from Kyowa Kirin, Gilead and Bristol Myers Squibb. S. Ito reports research funding from IQVIA, Meiji Seika Pharma, MSD, AstraZeneca, Abbvie, Amgen, Incyte, Otsuka, Gilead, Syneos Health Japan, Sanofi, Novartis, Zenyaku, Mitsubishi Tanabe, Chugai, Eli Lilly, Novartis, Bayer, Parexel, Pfizer, Bristol and Janssen. M. Kizaki has nothing to disclose. M. Yamaguchi has nothing to disclose. N. Fukuhara reports research funding from AbbVie, Bayer, Celgene, Chordia Therapeutics, Chugai, Genmab, Incyte, Kyowa-Kirin, LOXO Oncology, and Takeda. K. Kato reports research funding from AbbVie, Bristol Myers Squibb, Chugai, Daiichi Sankyo, Eisai, Janssen, Kyowa Kirin, Novartis, and Takeda. T. Saito reports research funding from AbbVie and Meiji Seika Pharma Co. Y. Terui reports lecture fees earned from AbbVie, Celgene, Chugai, Eisai, Janssen, Ono, and Symbio and contribution from Eisai. T. Soshin reports her and her husband\u2019s employment with AbbVie and may hold stock options or other ownership in AbbVie. N. Satomi reports employment with AbbVie and may hold stock options or other ownership in AbbVie. H. Honda reports employment with AbbVie and may hold stock options or other ownership in AbbVie. C. Qian reports employment with AbbVie and may hold stock options or other ownership in AbbVie. K. Izutsu reports consulting, research funding, and honoraria fees from AbbVie; honoraria and research funding from Janssen, Chugai, AstraZeneca, and Bristol Myers Squibb; and honoraria from Eli Lilly and Zenyaku.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}