{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T21:53:06Z","timestamp":1787003586048,"version":"build-2736575974"},"reference-count":39,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,7,27]],"date-time":"2024-07-27T00:00:00Z","timestamp":1722038400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,7,27]],"date-time":"2024-07-27T00:00:00Z","timestamp":1722038400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Genome Canada and Genome British Columbia","award":["G05CHS"],"award-info":[{"award-number":["G05CHS"]}]},{"name":"Genome Canada and Genome British Columbia","award":["271LYM"],"award-info":[{"award-number":["271LYM"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Costly targeted cancer treatments challenge publicly-funded healthcare systems seeking to align expected benefit with value for money. In 2021, The Canadian Agency for Drugs and Technologies in Health (CADTH) published a provisional funding algorithm for risk-based treatment of chronic lymphocytic leukemia (CLL). We estimate the cost-effectiveness of this algorithm against current standard of care. We constructed a probabilistic Markov model comparing next generation sequencing (NGS) assay-guided front-line treatment of acalabrutinib versus venetoclax with obinutuzumab to a comparator wherein patients initiate acalabrutinib. The primary outcome was the incremental cost-effectiveness ratio (ICER) per quality-adjusted life-year (QALY) gained. Analyses were conducted from the British Columbia healthcare system perspective, with outcomes discounted at 1.5%. Assay informed treatment for patients with CLL resulted in an incremental cost effectiveness ratio of $18,040 (95% CI $16,491\u2013$19,501) per quality adjusted life-year (QALY) gained. The probability of the NGS guided treatment algorithm being cost effective was 80% at a willingness to pay threshold of $50,000 and a corresponding ICER of $18,040. Assay-guided treatment sequencing adds additional costs to healthcare but may be a cost-effective intervention for adult patients with CLL. Integration of real-world evidence would improve the validity and reliability of model estimated for decision-makers.<\/jats:p>","DOI":"10.1038\/s41598-024-68431-6","type":"journal-article","created":{"date-parts":[[2024,7,27]],"date-time":"2024-07-27T08:02:01Z","timestamp":1722067321000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Assay-guided treatment sequencing in chronic lymphocytic leukemia (CLL): a cost-effectiveness analysis"],"prefix":"10.1038","volume":"14","author":[{"given":"Samantha","family":"Pollard","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brandon","family":"Chan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alina S.","family":"Gerrie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam J. N.","family":"Raymakers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dean A.","family":"Regier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,7,27]]},"reference":[{"key":"68431_CR1","doi-asserted-by":"publisher","first-page":"7","DOI":"10.3322\/caac.21708","volume":"72","author":"RL Siegel","year":"2022","unstructured":"Siegel, R. L., Miller, K. D., Fuchs, H. E. & Jemal, A. Cancer statistics, 2022. CA Cancer J. Clin. 72, 7\u201333. https:\/\/doi.org\/10.3322\/caac.21708 (2022).","journal-title":"CA Cancer J. Clin."},{"key":"68431_CR2","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/j.canep.2014.12.001","volume":"39","author":"Y Li","year":"2015","unstructured":"Li, Y., Wang, Y., Wang, Z., Yi, D. & Ma, S. Racial differences in three major NHL subtypes: Descriptive epidemiology. Cancer Epidemiol. 39, 8\u201313 (2015).","journal-title":"Cancer Epidemiol."},{"key":"68431_CR3","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1016\/j.critrevonc.2016.06.003","volume":"104","author":"L Scarf\u00f2","year":"2016","unstructured":"Scarf\u00f2, L., Ferreri, A. J. & Ghia, P. Chronic lymphocytic leukaemia. Crit. Rev. Oncol. Hematol. 104, 169\u2013182 (2016).","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"68431_CR4","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41408-021-00556-7","volume":"11","author":"H Kaj\u00fcter","year":"2021","unstructured":"Kaj\u00fcter, H. et al. Survival of patients with chronic lymphocytic leukemia before and after the introduction of chemoimmunotherapy in Germany. Blood Cancer J. 11, 1\u20134. https:\/\/doi.org\/10.1038\/s41408-021-00556-7 (2021).","journal-title":"Blood Cancer J."},{"key":"68431_CR5","doi-asserted-by":"publisher","first-page":"1946","DOI":"10.1182\/bloodadvances.2017015461","volume":"2","author":"JI Barnes","year":"2018","unstructured":"Barnes, J. I. et al. Cost-effectiveness of ibrutinib as first-line therapy for chronic lymphocytic leukemia in older adults without deletion 17p. Blood Adv. 2, 1946\u20131956 (2018).","journal-title":"Blood Adv."},{"key":"68431_CR6","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1200\/JOP.2014.002469","volume":"11","author":"TD Shanafelt","year":"2015","unstructured":"Shanafelt, T. D. et al. Impact of ibrutinib and idelalisib on the pharmaceutical cost of treating chronic lymphocytic leukemia at the individual and societal levels. J. Oncol. Pract. 11, 252\u2013258 (2015).","journal-title":"J. Oncol. Pract."},{"key":"68431_CR7","unstructured":"CADTH Reimbursement Review Provisional Funding Algorithm for Chronic Lymphocytic Leukemia. (2021)."},{"key":"68431_CR8","doi-asserted-by":"publisher","first-page":"460","DOI":"10.1056\/NEJMra1908213","volume":"383","author":"JA Burger","year":"2020","unstructured":"Burger, J. A. Treatment of chronic lymphocytic leukemia. N. Engl. J. Med. 383, 460\u2013473. https:\/\/doi.org\/10.1056\/NEJMra1908213 (2020).","journal-title":"N. Engl. J. Med."},{"key":"68431_CR9","doi-asserted-by":"publisher","first-page":"4042","DOI":"10.1200\/JCO.20.00948","volume":"38","author":"AP Kater","year":"2020","unstructured":"Kater, A. P. et al. Venetoclax plus rituximab in relapsed chronic lymphocytic leukemia: 4-year results and evaluation of impact of genomic complexity and gene mutations from the MURANO phase III study. J. Clin. Oncol. 38, 4042\u20134054. https:\/\/doi.org\/10.1200\/JCO.20.00948 (2020).","journal-title":"J. Clin. Oncol."},{"key":"68431_CR10","doi-asserted-by":"publisher","first-page":"1188","DOI":"10.1016\/S1470-2045(20)30443-5","volume":"21","author":"O Al-Sawaf","year":"2020","unstructured":"Al-Sawaf, O. et al. Venetoclax plus obinutuzumab versus chlorambucil plus obinutuzumab for previously untreated chronic lymphocytic leukaemia (CLL14): Follow-up results from a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 21, 1188\u20131200. https:\/\/doi.org\/10.1016\/S1470-2045(20)30443-5 (2020).","journal-title":"Lancet Oncol."},{"key":"68431_CR11","doi-asserted-by":"publisher","first-page":"2849","DOI":"10.1200\/JCO.19.03355","volume":"38","author":"P Ghia","year":"2020","unstructured":"Ghia, P. et al. ASCEND: Phase III, randomized trial of acalabrutinib versus idelalisib plus rituximab or bendamustine plus rituximab in relapsed or refractory chronic lymphocytic leukemia. J. Clin. Oncol. 38, 2849\u20132861. https:\/\/doi.org\/10.1200\/JCO.19.03355 (2020).","journal-title":"J. Clin. Oncol."},{"key":"68431_CR12","doi-asserted-by":"publisher","first-page":"1278","DOI":"10.1016\/S0140-6736(20)30262-2","volume":"395","author":"JP Sharman","year":"2020","unstructured":"Sharman, J. P. et al. Acalabrutinib with or without obinutuzumab versus chlorambucil and obinutuzumab for treatment-naive chronic lymphocytic leukaemia (ELEVATE-TN): A randomised, controlled, phase 3 trial. Lancet 395, 1278\u20131291. https:\/\/doi.org\/10.1016\/S0140-6736(20)30262-2 (2020).","journal-title":"Lancet"},{"key":"68431_CR13","doi-asserted-by":"publisher","first-page":"1391","DOI":"10.1016\/S1470-2045(21)00455-1","volume":"22","author":"MS Davids","year":"2021","unstructured":"Davids, M. S. et al. Acalabrutinib, venetoclax, and obinutuzumab as frontline treatment for chronic lymphocytic leukaemia: A single-arm, open-label, phase 2 study. Lancet Oncol. 22, 1391\u20131402 (2021).","journal-title":"Lancet Oncol."},{"key":"68431_CR14","doi-asserted-by":"publisher","first-page":"2849","DOI":"10.1200\/JCO.19.03355","volume":"38","author":"P Ghia","year":"2020","unstructured":"Ghia, P. et al. ASCEND: Phase III, randomized trial of acalabrutinib versus idelalisib plus rituximab or bendamustine plus rituximab in relapsed or refractory chronic lymphocytic leukemia. J. Clin. Oncol. 38, 2849\u20132861 (2020).","journal-title":"J. Clin. Oncol."},{"key":"68431_CR15","doi-asserted-by":"publisher","first-page":"3432","DOI":"10.1080\/10428194.2020.1811271","volume":"61","author":"Z Sheng","year":"2020","unstructured":"Sheng, Z. et al. Comparison of acalabrutinib plus obinutuzumab, ibrutinib plus obinutuzumab and venetoclax plus obinutuzumab for untreated CLL: A network meta-analysis. Leukemia Lymphoma 61, 3432\u20133439 (2020).","journal-title":"Leukemia Lymphoma"},{"key":"68431_CR16","unstructured":"Final Recommendation for Acalabrutinib (Calquence) for Previously Untreated Chronic Lymphocytic Leukemia. (Canadian Agency for Drugs and Technologies in Health, 2021)."},{"key":"68431_CR17","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1182\/blood-2020-137688","volume":"136","author":"T Munir","year":"2020","unstructured":"Munir, T., Gaitonde, P. & Waweru, C. Cost-effectiveness of acalabrutinib monotherapy compared with chlorambucil plus obinutuzumab for previously untreated chronic lymphocytic leukemia. Blood 136, 13\u201314 (2020).","journal-title":"Blood"},{"key":"68431_CR18","doi-asserted-by":"publisher","first-page":"1685","DOI":"10.1016\/j.jval.2022.04.001","volume":"25","author":"N Alrawashdh","year":"2022","unstructured":"Alrawashdh, N. et al. Cost-effectiveness and economic burden analyses on all first-line treatments of chronic lymphocytic leukemia. Value Health 25, 1685\u20131695 (2022).","journal-title":"Value Health"},{"key":"68431_CR19","doi-asserted-by":"crossref","unstructured":"Gribben, J. G. The molecular biology of chronic lymphocytic leukemia. In Molecular Hematology, 111\u2013120 (2019).","DOI":"10.1002\/9781119252863.ch9"},{"key":"68431_CR20","doi-asserted-by":"publisher","first-page":"1679","DOI":"10.1002\/ajh.26367","volume":"96","author":"M Hallek","year":"2021","unstructured":"Hallek, M. & Al-Sawaf, O. Chronic lymphocytic leukemia: 2022 update on diagnostic and therapeutic procedures. Am. J. Hematol. 96, 1679\u20131705 (2021).","journal-title":"Am. J. Hematol."},{"key":"68431_CR21","doi-asserted-by":"publisher","first-page":"779","DOI":"10.1016\/S1470-2045(16)30029-8","volume":"17","author":"Group, I. C.-I. W.","year":"2016","unstructured":"Group, I. C.-I. W. An international prognostic index for patients with chronic lymphocytic leukaemia (CLL-IPI): A meta-analysis of individual patient data. Lancet Oncol. 17, 779\u2013790 (2016).","journal-title":"Lancet Oncol."},{"key":"68431_CR22","doi-asserted-by":"publisher","first-page":"787","DOI":"10.1038\/s41375-019-0602-x","volume":"34","author":"JA Burger","year":"2020","unstructured":"Burger, J. A. et al. Long-term efficacy and safety of first-line ibrutinib treatment for patients with CLL\/SLL: 5 years of follow-up from the phase 3 RESONATE-2 study. Leukemia 34, 787\u2013798. https:\/\/doi.org\/10.1038\/s41375-019-0602-x (2020).","journal-title":"Leukemia"},{"key":"68431_CR23","doi-asserted-by":"publisher","first-page":"410","DOI":"10.1182\/blood-2017-02-734541","volume":"130","author":"J Taylor","year":"2017","unstructured":"Taylor, J., Xiao, W. & Abdel-Wahab, O. Diagnosis and classification of hematologic malignancies on the basis of genetics. Blood 130, 410\u2013423. https:\/\/doi.org\/10.1182\/blood-2017-02-734541 (2017).","journal-title":"Blood"},{"key":"68431_CR24","doi-asserted-by":"publisher","first-page":"1664","DOI":"10.1038\/s41588-022-01140-w","volume":"54","author":"BA Knisbacher","year":"2022","unstructured":"Knisbacher, B. A. et al. Molecular map of chronic lymphocytic leukemia and its impact on outcome. Nat. Genet. 54, 1664\u20131674 (2022).","journal-title":"Nat. Genet."},{"key":"68431_CR25","unstructured":"Guidelines for the Economic Evaluation of Health Technologies in Canada. (Canadian Agency for Drugs and Technologies in Health, 2017)."},{"key":"68431_CR26","unstructured":"Chan, B. Edamame. Version 1.0.0. , https:\/\/github.com\/BrandonCChan\/edamame (2022)."},{"key":"68431_CR27","doi-asserted-by":"publisher","first-page":"4305","DOI":"10.1182\/blood-2019-126542","volume":"134","author":"O Al-Sawaf","year":"2019","unstructured":"Al-Sawaf, O. et al. Rapid improvement of patient-reported outcomes with venetoclax plus obinutuzumab in patients with previously untreated CLL and coexisting conditions: A prospective analysis from the CLL14 trial. Blood 134, 4305\u20134305. https:\/\/doi.org\/10.1182\/blood-2019-126542 (2019).","journal-title":"Blood"},{"key":"68431_CR28","doi-asserted-by":"publisher","first-page":"1391","DOI":"10.1200\/JCO.18.01460","volume":"37","author":"JP Sharman","year":"2019","unstructured":"Sharman, J. P. et al. Final results of a randomized, phase III study of rituximab with or without idelalisib followed by open-label idelalisib in patients with relapsed chronic lymphocytic leukemia. J. Clin. Oncol. 37, 1391\u20131402. https:\/\/doi.org\/10.1200\/JCO.18.01460 (2019).","journal-title":"J. Clin. Oncol."},{"key":"68431_CR29","doi-asserted-by":"publisher","first-page":"1107","DOI":"10.1056\/NEJMoa1713976","volume":"378","author":"JF Seymour","year":"2018","unstructured":"Seymour, J. F. et al. Venetoclax-rituximab in relapsed or refractory chronic lymphocytic leukemia. N. Engl. J. Med. 378, 1107\u20131120. https:\/\/doi.org\/10.1056\/NEJMoa1713976 (2018).","journal-title":"N. Engl. J. Med."},{"key":"68431_CR30","doi-asserted-by":"crossref","unstructured":"Beusterien, K. M. et al. RPeoseaprcuh lation preference values for treatment outcomes in chronic lymphocytic leukaemia: A cross-sectional utility study. 9 (2010).","DOI":"10.1186\/1477-7525-8-50"},{"key":"68431_CR31","first-page":"E191","volume":"8","author":"N Mittmann","year":"2020","unstructured":"Mittmann, N. et al. Health system costs for cancer medications and radiation treatment in Ontario for the 4 most common cancers: A retrospective cohort study. Can. Med. Assoc. Open Access J. 8, E191\u2013E198 (2020).","journal-title":"Can. Med. Assoc. Open Access J."},{"key":"68431_CR32","doi-asserted-by":"publisher","first-page":"1285","DOI":"10.1200\/JCO.18.02403","volume":"37","author":"A Younes","year":"2019","unstructured":"Younes, A. et al. Randomized phase III trial of ibrutinib and rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone in non-germinal center B-cell diffuse large B-cell lymphoma. J. Clin. Oncol. 37, 1285\u20131295. https:\/\/doi.org\/10.1200\/JCO.18.02403 (2019).","journal-title":"J. Clin. Oncol."},{"key":"68431_CR33","doi-asserted-by":"publisher","first-page":"908","DOI":"10.3390\/cancers14040908","volume":"14","author":"DA Regier","year":"2022","unstructured":"Regier, D. A. et al. Cost-effectiveness of molecularly guided treatment in diffuse large B-cell lymphoma (DLBCL) in patients under 60. Cancers 14, 908 (2022).","journal-title":"Cancers"},{"key":"68431_CR34","doi-asserted-by":"publisher","first-page":"864","DOI":"10.1111\/bjh.16777","volume":"190","author":"L Calvente","year":"2020","unstructured":"Calvente, L. et al. Validation of the RHL30 digital gene expression assay as a prognostic biomarker for relapsed Hodgkin lymphoma. Br. J. Haematol. 190, 864\u2013868. https:\/\/doi.org\/10.1111\/bjh.16777 (2020).","journal-title":"Br. J. Haematol."},{"key":"68431_CR35","doi-asserted-by":"publisher","first-page":"2155","DOI":"10.1182\/blood-2022-156948","volume":"140","author":"N Alrawashdh","year":"2022","unstructured":"Alrawashdh, N., McBride, A. & Abraham, I. Cost-effectiveness analyses of first line ibrutinib versus acalabrutinib versus zanubrutinib followed by second line venetoclax plus rituximab in previously untreated chronic lymphocytic leukemia (CLL) patients. Blood 140, 2155\u20132156 (2022).","journal-title":"Blood"},{"key":"68431_CR36","doi-asserted-by":"crossref","unstructured":"Chatterjee, A. et al. A Probabilistic cost-effectiveness analysis of venetoclax and obinutuzumab as a first-line therapy in chronic lymphocytic leukemia in Canada. PharmacoEconomics-Open, 1\u201318 (2022).","DOI":"10.1007\/s41669-022-00375-x"},{"issue":"4","key":"68431_CR37","doi-asserted-by":"publisher","first-page":"560","DOI":"10.1002\/ajh.26864","volume":"98","author":"MS Kim","year":"2023","unstructured":"Kim, M. S. & Prasad, V. Front-line CLL: The role of chemoimmunotherapy. Am. J. Hematol. 98(4), 560\u2013561 (2023).","journal-title":"Am. J. Hematol."},{"key":"68431_CR38","doi-asserted-by":"publisher","first-page":"1171","DOI":"10.1038\/s41375-021-01485-x","volume":"36","author":"JP Sharman","year":"2022","unstructured":"Sharman, J. P. et al. Efficacy and safety in a 4-year follow-up of the ELEVATE-TN study comparing acalabrutinib with or without obinutuzumab versus obinutuzumab plus chlorambucil in treatment-na\u00efve chronic lymphocytic leukemia. Leukemia 36, 1171\u20131175 (2022).","journal-title":"Leukemia"},{"key":"68431_CR39","doi-asserted-by":"publisher","first-page":"833","DOI":"10.1080\/17474086.2022.2125376","volume":"15","author":"L Gao","year":"2022","unstructured":"Gao, L., Nguyen, D. & Lee, P. A systematic review of economic evaluations for the pharmaceutical treatment of chronic lymphocytic leukemia and acute myeloid leukemia. Expert Rev. Hematol. 15, 833\u2013847 (2022).","journal-title":"Expert Rev. Hematol."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-68431-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-68431-6","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-68431-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,27]],"date-time":"2024-07-27T08:07:10Z","timestamp":1722067630000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-68431-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,27]]},"references-count":39,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["68431"],"URL":"https:\/\/doi.org\/10.1038\/s41598-024-68431-6","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,27]]},"assertion":[{"value":"2 June 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 July 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 July 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Samantha Pollard has received personal fees from Roche Canada, Bitota Economics Group, and AstraZeneca Canada, as co-director at IMPRINT Research Consulting Ltd outside the submitted work.\u00a0Adam Raymakers reports currently serving as a member of the pan-Canadian Oncology Drug Review Expert Review Committee (pERC) within the Canadian Agency for Drugs and Technologies in Health (CADTH). Alina S Gerrie has received institutional research funding from Janssen, AstraZeneca, Abbvie, and Roche Canada, honoraria from Janssen, Astrazeneca, Abbvie, and Beigene, and has served as a clinical expert for CADTH. Dean A Regier has received travel funding from Illumina; his institution has received research funding for a project from Roche Canada. Brandon Chan has no competing interests to declare.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"17294"}}