{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T02:13:05Z","timestamp":1791252785128,"version":"4.1.0"},"reference-count":27,"publisher":"Springer Science and Business Media LLC","issue":"10","license":[{"start":{"date-parts":[[2024,7,17]],"date-time":"2024-07-17T00:00:00Z","timestamp":1721174400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,7,17]],"date-time":"2024-07-17T00:00:00Z","timestamp":1721174400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100006447","name":"University of Zurich","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100006447","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Ann Hematol"],"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Further line treatment of patients with advanced stage AL amyloidosis with cardiac involvement is challenging. Venetoclax is a promising option, especially in t(11;14) and BCL2 expression.<\/jats:p><jats:p>In our multicentre observational study, we report the 3-year follow-up of Venetoclax treatment in 9 patients with advanced, relapsed or refractory AL amyloidosis with t(11;14) and BCL-2 expression in\u2009&gt;\u200950% of plasma cells. At baseline, all patients had been previously treated with daratumumab, all had cardiac involvement with revised Mayo stage III or IV\/ European modification of Mayo 2004 IIIA or IIIB (1\/9 unclassified due to missing troponin T), 5\/9 patients had renal involvement.<\/jats:p><jats:p>After a median of 35\u00a0months (range 25\u201349) since the start of Venetoclax, 8\/9 patients were still alive (OS 89%). First and best hematological responses were observed after a median of 26\u00a0days (11\u2013125) and 106\u00a0days (35\u2013659), overall response rate was 100% (7\/9 CR, 2\/9 VGPR). Where observed, organ response was documented within the first 6\u00a0months of therapy, including cardiac (6\/9) and renal (3\/5) improvements. Venetoclax was discontinued in 6\/9 patients after a median of 15\u00a0months (11\u201348) due to toxicity (2\/9), disease progression (2\/9), fixed treatment duration (1\/9), or safety concerns (1\/9).<\/jats:p><jats:p>In conclusion, Venetoclax induces a rapid and deep hematologic response with consistent improvement in organ function with an acceptable safety profile in patients with pretreated, advanced stage AL amyloidosis with cardiac involvement and BCL2 expression with and potentially without detected t(11:14), which warrants further investigation.<\/jats:p>","DOI":"10.1007\/s00277-024-05901-x","type":"journal-article","created":{"date-parts":[[2024,7,17]],"date-time":"2024-07-17T16:02:09Z","timestamp":1721232129000},"page":"4163-4170","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Three years follow-up of Venetoclax in advanced-stage, relapsed or refractory AL amyloidosis with cardiac involvement and t(11;14) with BCL2 expression"],"prefix":"10.1007","volume":"103","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8441-4547","authenticated-orcid":false,"given":"Max J.","family":"Rieger","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Pabst","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Jeker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamella","family":"Paul","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio","family":"Bergamini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco M.","family":"B\u00fchler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adalgisa","family":"Condoluci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas J.","family":"Flammer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davide","family":"Rossi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georg","family":"Stussi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernhard","family":"Gerber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rahel","family":"Schwotzer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,7,17]]},"reference":[{"key":"5901_CR1","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1016\/j.ijcard.2021.04.023","volume":"335","author":"M Zampieri","year":"2021","unstructured":"Zampieri M, Nardi G, Del Monaco G, Allinovi M, Gabriele M, Zocchi C, Casagrande S, Fumagalli C, Di Mario C, Olivotto I, Perfetto F, Cappelli F (2021) Changes in the perceived epidemiology of amyloidosis: 20 year-experience from a Tertiary Referral Centre in Tuscany. Int J Cardiol. 335:123\u2013127. https:\/\/doi.org\/10.1016\/j.ijcard.2021.04.023","journal-title":"Int J Cardiol."},{"key":"5901_CR2","doi-asserted-by":"publisher","first-page":"No. 2","DOI":"10.57187\/s.3485","volume":"vol. 154","author":"S Brouwers","year":"2024","unstructured":"Brouwers S et al (2024) \u201cHistoric characteristics and mortality of patients in the Swiss Amyloidosis Registry,.\u201d Swiss Med. Wkly. 154:No. 2","journal-title":"Swiss Med. Wkly."},{"key":"5901_CR3","doi-asserted-by":"publisher","first-page":"no. 4","DOI":"10.1159\/000508287","volume":"vol. 143","author":"T Dittrich","year":"2020","unstructured":"Dittrich T, Kimmich C, Hegenbart U, Sch\u00f6nland SO (2020) \u201cPrognosis and staging of AL amyloidosis,.\u201d Acta Haematologica 143:no. 4","journal-title":"Acta Haematologica"},{"issue":"9","key":"5901_CR4","doi-asserted-by":"publisher","first-page":"989","DOI":"10.1200\/JCO.2011.38.5724","volume":"30","author":"S Kumar","year":"2012","unstructured":"Kumar S, Dispenzieri A, Lacy MQ, Hayman SR, Buadi FK, Colby C, Laumann K, Zeldenrust SR, Leung N, Dingli D, Greipp PR, Lust JA, Russell SJ, Kyle RA, Rajkumar SV, Gertz MA (2012) Revised prognostic staging system for light chain amyloidosis incorporating cardiac biomarkers and serum free light chain measurements. J Clin Oncol. 30(9):989\u201395. https:\/\/doi.org\/10.1200\/JCO.2011.38.5724","journal-title":"J Clin Oncol."},{"key":"5901_CR5","doi-asserted-by":"publisher","first-page":"no. 1","DOI":"10.1056\/NEJMoa2028631","volume":"vol. 385","author":"E Kastritis","year":"2021","unstructured":"Kastritis E et al (2021) \u201cDaratumumab-Based Treatment for Immunoglobulin Light-Chain Amyloidosis,.\u201d N. Engl. J. Med. 385:no. 1","journal-title":"N. Engl. J. Med."},{"issue":"15_suppl","key":"5901_CR6","doi-asserted-by":"publisher","first-page":"8003","DOI":"10.1200\/JCO.2021.39.15_suppl.8003","volume":"39","author":"E Kastritis","year":"2021","unstructured":"Kastritis E, Sanchorawala V, Merlini G, on behalf of the ANDROMEDA study group (2021) Subcutaneous daratumumab + bortezomib, cyclophosphamide, and dexamethasone (VCd) in patients with newly diagnosed light chain (AL) amyloidosis: Updated results from the phase 3 ANDROMEDA study. J Clin Oncol 39(15_suppl):8003\u20138003. https:\/\/doi.org\/10.1200\/JCO.2021.39.15_suppl.8003","journal-title":"J Clin Oncol"},{"key":"5901_CR7","doi-asserted-by":"publisher","first-page":"no. 1","DOI":"10.1080\/13506129.2022.2093635","volume":"vol. 30","author":"AD Wechalekar","year":"2023","unstructured":"Wechalekar AD et al (2023) \u201cGuidelines for non-transplant chemotherapy for treatment of systemic AL amyloidosis: EHA-ISA working group,.\u201d Amyloid 30:no. 1","journal-title":"Amyloid"},{"issue":"4","key":"5901_CR8","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1080\/13506129.2018.1540410","volume":"25","author":"E Kastritis","year":"2018","unstructured":"Kastritis E, Gavriatopoulou M, Roussou M, Bagratuni T, Migkou M, Fotiou D, Ziogas DC, Kanellias N, Eleutherakis-Papaiakovou E, Dialoupi I, Ntanasis-Stathopoulos I, Spyropoulou-Vlachou M, Psimenou E, Gakiopoulou H, Marinaki S, Papadopoulou E, Ntalianis A, Terpos E, Dimopoulos MA (2018) Efficacy of lenalidomide as salvage therapy for patients with AL amyloidosis. Amyloid 25(4):234\u2013241. https:\/\/doi.org\/10.1080\/13506129.2018.1540410","journal-title":"Amyloid"},{"key":"5901_CR9","first-page":"no.Suppl 1","volume":"vol. 130","author":"C Kimmich","year":"2017","unstructured":"Kimmich C et al (2017) \u201cDaratumumab Monotherapy in Thirty-Two Heavily Pre-Treated Patients with Advanced Systemic Light-Chain Amyloidosis,.\u201d Blood 130:no.Suppl 1","journal-title":"Blood"},{"issue":"3","key":"5901_CR10","doi-asserted-by":"publisher","first-page":"881","DOI":"10.1093\/ndt\/gfq482","volume":"26","author":"R Specter","year":"2011","unstructured":"Specter R, Sanchorawala V, Seldin DC, Shelton A, Fennessey S, Finn KT, Zeldis JB, Dember LM (2011) Kidney dysfunction during lenalidomide treatment for AL amyloidosis. Nephrol Dial Transplant. 26(3):881\u20136. https:\/\/doi.org\/10.1093\/ndt\/gfq482","journal-title":"Nephrol Dial Transplant."},{"key":"5901_CR11","doi-asserted-by":"publisher","first-page":"no. 7","DOI":"10.1002\/cam4.5621","volume":"vol. 12","author":"H Fishov","year":"2023","unstructured":"Fishov H et al (2023) \u201cAL amyloidosis clonal plasma cells are regulated by microRNAs and dependent on anti-apoptotic BCL2 family members,.\u201d Cancer Med 12:no. 7","journal-title":"Cancer Med"},{"key":"5901_CR12","doi-asserted-by":"publisher","first-page":"no. 1","DOI":"10.1038\/s41467-022-33461-z","volume":"vol. 13","author":"CS Fraser","year":"2022","unstructured":"Fraser CS et al (2022) \u201cExploiting endogenous and therapy-induced apoptotic vulnerabilities in immunoglobulin light chain amyloidosis with BH3 mimetics,.\u201d Nat. Commun 13:no. 1","journal-title":"Nat. Commun"},{"issue":"12","key":"5901_CR13","doi-asserted-by":"publisher","first-page":"1371","DOI":"10.1200\/JCO.2014.57.4947","volume":"33","author":"T Bochtler","year":"2015","unstructured":"Bochtler T, Hegenbart U, Kunz C, Granzow M, Benner A, Seckinger A, Kimmich C, Goldschmidt H, Ho AD, Hose D, Jauch A, Sch\u00f6nland SO (2015) Translocation t(11;14) is associated with adverse outcome in patients with newly diagnosed AL amyloidosis when treated with bortezomib-based regimens. J Clin Oncol. 33(12):1371\u20138. https:\/\/doi.org\/10.1200\/JCO.2014.57.4947","journal-title":"J Clin Oncol."},{"key":"5901_CR14","doi-asserted-by":"publisher","first-page":"no. 3","DOI":"10.3324\/haematol.2017.183749","volume":"vol. 103","author":"N Leung","year":"2018","unstructured":"Leung N, Thom\u00e9 SD, Dispenzieri A (2018) \u201cVenetoclax induced a complete response in a patient with immunoglobulin light chain amyloidosis plateaued on cyclophosphamide, bortezomib and dexamethasone,.\u201d Haematologica 103:no. 3","journal-title":"Haematologica"},{"key":"5901_CR15","doi-asserted-by":"publisher","first-page":"no. 3","DOI":"10.1080\/13506129.2019.1615428","volume":"vol. 26","author":"G Ghilardi","year":"2019","unstructured":"Ghilardi G, Stussi G, Mazzucchelli L, R\u00f6cken C, Rossi D, Gerber B (2019) \u201cVenetoclax plus daratumumab induce hematological CR and organ response in an AL amyloidosis patient with t(11;14),.\u201d Amyloid 26:no. 3","journal-title":"Amyloid"},{"key":"5901_CR16","doi-asserted-by":"publisher","first-page":"no. 5","DOI":"10.1038\/s41408-020-0321-6","volume":"vol. 10","author":"MH Sidiqi","year":"2020","unstructured":"Sidiqi MH et al (2020) \u201cVenetoclax for the treatment of translocation (11;14) AL amyloidosis,.\u201d Blood Cancer Journal 10:no. 5","journal-title":"Blood Cancer Journal"},{"key":"5901_CR17","doi-asserted-by":"publisher","first-page":"no. 3","DOI":"10.1111\/bjh.17380","volume":"vol. 193","author":"H Pasquer","year":"2021","unstructured":"Pasquer H et al (2021) \u201cVenetoclax induces profound and sustained responses in patients with relapsed\/refractory light-chain amyloidosis,.\u201d British Journal of Haematology 193:no. 3","journal-title":"British Journal of Haematology"},{"key":"5901_CR18","first-page":"vol. 11","volume":"no. 1","author":"VJ Premkumar","year":"2021","unstructured":"Premkumar VJ et al (vol.11) \u201cVenetoclax induces deep hematologic remissions in t(11;14) relapsed\/refractory AL amyloidosis,.\u201d Blood Cancer J. no. 1:2021","journal-title":"Blood Cancer J."},{"issue":"36","key":"5901_CR19","doi-asserted-by":"publisher","first-page":"4541","DOI":"10.1200\/JCO.2011.37.7614","volume":"30","author":"G Palladini","year":"2012","unstructured":"Palladini G, Dispenzieri A, Gertz MA, Kumar S, Wechalekar A, Hawkins PN, Sch\u00f6nland S, Hegenbart U, Comenzo R, Kastritis E, Dimopoulos MA, Jaccard A, Klersy C, Merlini G (2012) New criteria for response to treatment in immunoglobulin light chain amyloidosis based on free light chain measurement and cardiac biomarkers: impact on survival outcomes. J Clin Oncol. 30(36):4541\u20139. https:\/\/doi.org\/10.1200\/JCO.2011.37.7614","journal-title":"J Clin Oncol."},{"key":"5901_CR20","doi-asserted-by":"publisher","first-page":"no. 6","DOI":"10.3390\/cancers15061710","volume":"vol. 15","author":"E Lebel","year":"2023","unstructured":"Lebel E et al (2023) \u201cVenetoclax in Relapse\/Refractory AL Amyloidosis\u2014A Multicenter International Retrospective Real-World Study,.\u201d Cancers (Basel) 15:no. 6","journal-title":"Cancers (Basel)"},{"key":"5901_CR21","doi-asserted-by":"crossref","first-page":"no. 12","DOI":"10.1016\/S1470-2045(19)30805-8","volume":"vol. 21","author":"SK Kumar","year":"2020","unstructured":"Kumar SK (2020) \u201cVenetoclax or placebo in combination with bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma (BELLINI): a randomised, double-blind, multicentre, phase 3 trial,.\u201d Lancet Oncol 21:no. 12","journal-title":"Lancet Oncol"},{"issue":"4","key":"5901_CR22","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1002\/ajh.20381","volume":"79","author":"MA Gertz","year":"2005","unstructured":"Gertz MA, Comenzo R, Falk RH, Fermand JP, Hazenberg BP, Hawkins PN, Merlini G, Moreau P, Ronco P, Sanchorawala V, Sezer O, Solomon A, Grateau G (2005) Definition of organ involvement and treatment response in immunoglobulin light chain amyloidosis (AL): a consensus opinion from the 10th International Symposium on Amyloid and Amyloidosis, Tours, France, 18\u201322 April 2004. Am J Hematol. 79(4):319\u201328. https:\/\/doi.org\/10.1002\/ajh.20381","journal-title":"Am J Hematol."},{"issue":"10","key":"5901_CR23","doi-asserted-by":"publisher","first-page":"2240","DOI":"10.1038\/s41375-018-0060-x","volume":"32","author":"E Muchtar","year":"2018","unstructured":"Muchtar E, Dispenzieri A, Leung N, Lacy MQ, Buadi FK, Dingli D, Grogan M, Hayman SR, Kapoor P, Hwa YL, Fonder A, Hobbs M, Chakraborty R, Gonsalves W, Kourelis TV, Warsame R, Russell S, Lust JA, Lin Y, Go RS, Zeldenrust S, Kyle RA, Rajkumar SV, Kumar SK, Gertz MA (2018) Depth of organ response in AL amyloidosis is associated with improved survival: grading the organ response criteria. Leukemia. 32(10):2240\u20132249. https:\/\/doi.org\/10.1038\/s41375-018-0060-x","journal-title":"Leukemia."},{"key":"5901_CR24","doi-asserted-by":"publisher","first-page":"no. 6","DOI":"10.1002\/ajh.26569","volume":"vol. 97","author":"MA Gertz","year":"2022","unstructured":"Gertz MA (2022) \u201cImmunoglobulin light chain amyloidosis: 2022 update on diagnosis, prognosis, and treatment,.\u201d Am. J. Hematol., 97(6)","journal-title":"Am. J. Hematol.,"},{"issue":"17","key":"5901_CR25","doi-asserted-by":"publisher","first-page":"3420","DOI":"10.1182\/blood-2012-12-473066","volume":"121","author":"AD Wechalekar","year":"2013","unstructured":"Wechalekar AD, Schonland SO, Kastritis E, Gillmore JD, Dimopoulos MA, Lane T, Foli A, Foard D, Milani P, Rannigan L, Hegenbart U, Hawkins PN, Merlini G, Palladini G (2013) A European collaborative study of treatment outcomes in 346 patients with cardiac stage III AL amyloidosis. Blood. 121(17):3420\u20137. https:\/\/doi.org\/10.1182\/blood-2012-12-473066","journal-title":"Blood."},{"key":"5901_CR26","first-page":"no. 4","volume":"vol.96","author":"JL Kaufman","year":"2021","unstructured":"Kaufman JL (2021) \u201cTargeting BCL-2 with venetoclax and dexamethasone in patients with relapsed\/refractory t(11;14) multiple myeloma,.\u201d Am. J. Hematol., vol. 96, no. 4, 2021. vol.96:no. 4","journal-title":"Am. J. Hematol., vol. 96, no. 4, 2021."},{"key":"5901_CR27","doi-asserted-by":"publisher","first-page":"no. Supplement_","DOI":"10.1182\/blood-2019-126094","volume":"vol. 134","author":"S Harrison","year":"2019","unstructured":"Harrison S et al (2019) \u201cT(11;14) and High BCL2 Expression Are Predictive Biomarkers of Response to Venetoclax in Combination with Bortezomib and Dexamethasone in Patients with Relapsed\/Refractory Multiple Myeloma: Biomarker Analyses from the Phase 3 Bellini Study,.\u201d Blood 134:no. Supplement_1","journal-title":"Blood"}],"container-title":["Annals of Hematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00277-024-05901-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00277-024-05901-x\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00277-024-05901-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,26]],"date-time":"2024-10-26T09:05:35Z","timestamp":1729933535000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00277-024-05901-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,17]]},"references-count":27,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2024,10]]}},"alternative-id":["5901"],"URL":"https:\/\/doi.org\/10.1007\/s00277-024-05901-x","relation":{},"ISSN":["0939-5555","1432-0584"],"issn-type":[{"value":"0939-5555","type":"print"},{"value":"1432-0584","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,17]]},"assertion":[{"value":"10 June 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 July 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 July 2024","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 local ethics committee (\u201ccomitato etico cantonale\u201d) granted ethical approval for the substudy (Req-2022\u201302088) in accordance with the principles of the Declaration of Helsinki.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics Approval"}},{"value":"MR, RS, BG, TP, IR, PP, FB, MB, AC, DR, and GS report no competing financial interests related to this article. AJF declares fees from Alnylam, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Fresenius, Imedos Systems, Medtronic, MSD, Mundipharma, Novartis, Pierre Fabre, Pfizer, Roche, Schwabe Pharma, Vifor, and Zoll, as well as grant support by Novartis, AstraZeneca and Berlin Heart unrelated to this article.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of Interest"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"All patients gave informed consent according to local practice.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Patient consent statement"}},{"value":"N\/a.","order":6,"name":"Ethics","group":{"name":"EthicsHeading","label":"Permission to reproduce material from other sources"}},{"value":"N\/a.","order":7,"name":"Ethics","group":{"name":"EthicsHeading","label":"Clinical trial registration"}}]}}