{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T06:19:08Z","timestamp":1782973148676,"version":"3.54.5"},"reference-count":40,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2023,9,2]],"date-time":"2023-09-02T00:00:00Z","timestamp":1693612800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>This real-world analysis investigated patients with follicular lymphoma in Italy receiving three or more treatment lines (\u22653L), focusing on therapeutic pathways with their rebounds on healthcare resource consumptions and costs. Data were retrieved from administrative databases from healthcare entities covering about 13.3 million residents. Adults diagnosed with follicular lymphoma were identified between January 2015 and June 2020, and among them 2434 patients with \u22653L of treatment during the data availability interval (January 2009 to June 2021) were included. Of them, 1318 were in 3L, 494 in 4L and 622 in \u22655L. A relevant proportion of patients (12\u201332%) switched to a later line within the same calendar year. At 3-year follow-up (median), 34% patients died. Total mean annual expenses were euro 14,508 in the year preceding inclusion and rose to euro 21,081 at 1-year follow-up (on average euro 22,230\/patient\/year for the whole follow-up), with hospitalization and drug expenses as weightiest cost items. In conclusion, the clinical and economic burden of follicular lymphoma increases along with later treatment lines. The high mortality rates indicate that further efforts are needed to optimize disease management.<\/jats:p>","DOI":"10.3390\/cancers15174403","type":"journal-article","created":{"date-parts":[[2023,9,4]],"date-time":"2023-09-04T02:43:20Z","timestamp":1693795400000},"page":"4403","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Burden of Illness in Follicular Lymphoma with Multiple Lines of Treatment, Italian RWE Analysis"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9606-6124","authenticated-orcid":false,"given":"Andr\u00e9s J. M.","family":"Ferreri","sequence":"first","affiliation":[{"name":"Unit\u00e0 Linfomi, IRCCS Ospedale San Raffaele, 20132 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2112-2651","authenticated-orcid":false,"given":"Pier Luigi","family":"Zinzani","sequence":"additional","affiliation":[{"name":"Istituto di Ematologia \u201cSer\u00e0gnoli\u201d, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy"},{"name":"Dipartimento di Scienze Mediche e Chirurgiche, Universit\u00e0 di Bologna, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo","family":"Messina","sequence":"additional","affiliation":[{"name":"Novartis Farma S.p.A., 20154 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diletta","family":"Valsecchi","sequence":"additional","affiliation":[{"name":"Novartis Farma S.p.A., 20154 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Chiara","family":"Rendace","sequence":"additional","affiliation":[{"name":"Novartis Farma S.p.A., 20154 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleonora","family":"Premoli","sequence":"additional","affiliation":[{"name":"Novartis Farma S.p.A., 20154 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Giacomini","sequence":"additional","affiliation":[{"name":"CliCon S.r.l. Societ\u00e0 Benefit, Health, Economics & Outcomes Research, Via Murri, 40137 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2852-2022","authenticated-orcid":false,"given":"Chiara","family":"Veronesi","sequence":"additional","affiliation":[{"name":"CliCon S.r.l. Societ\u00e0 Benefit, Health, Economics & Outcomes Research, Via Murri, 40137 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7020-6659","authenticated-orcid":false,"given":"Luca","family":"Degli Esposti","sequence":"additional","affiliation":[{"name":"CliCon S.r.l. Societ\u00e0 Benefit, Health, Economics & Outcomes Research, Via Murri, 40137 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-4613-1500","authenticated-orcid":false,"given":"Paola","family":"Di Matteo","sequence":"additional","affiliation":[{"name":"Novartis Farma S.p.A., 20154 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,2]]},"reference":[{"key":"ref_1","unstructured":"Kaseb, H., Ali, M.A., and Koshy, N.V. (2023, April 14). Follicular Lymphoma, StatPearls, Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK538206\/."},{"key":"ref_2","unstructured":"Sapkota, S., and Shaikh, H. (2023, May 15). Non-Hodgkin Lymphoma, StatPearls, Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK559328\/."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1080\/10428194.2021.1975188","article-title":"Epidemiology of diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) in the United States and Western Europe: Population-level projections for 2020\u20132025","volume":"63","author":"Kanas","year":"2022","journal-title":"Leuk. Lymphoma"},{"key":"ref_4","first-page":"539","article-title":"Epidemiology of malignant lymphomas in Italy","volume":"5","author":"Piccaluga","year":"2021","journal-title":"Open Access J. Oncol. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e481","DOI":"10.1016\/S2352-3026(15)00155-6","article-title":"Changes in dynamics of excess mortality rates and net survival after diagnosis of follicular lymphoma or diffuse large B-cell lymphoma: Comparison between European population-based data (EUROCARE-5)","volume":"2","author":"Mounier","year":"2015","journal-title":"Lancet Haematol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"19","DOI":"10.3324\/haematol.2021.278717","article-title":"Prospects in the management of patients with follicular lymphoma beyond first-line therapy","volume":"107","author":"Qualls","year":"2022","journal-title":"Haematologica"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1016\/S1470-2045(14)70027-0","article-title":"Rituximab versus a watch-and-wait approach in patients with advanced-stage, asymptomatic, non-bulky follicular lymphoma: An open-label randomised phase 3 trial","volume":"15","author":"Ardeshna","year":"2014","journal-title":"Lancet Oncol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"v83","DOI":"10.1093\/annonc\/mdw400","article-title":"Newly diagnosed and relapsed follicular lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up","volume":"27","author":"Dreyling","year":"2016","journal-title":"Ann. Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1080\/14737140.2023.2171994","article-title":"A 24-month updated analysis of the comparative effectiveness of ZUMA-5 (axi-cel) vs. SCHOLAR-5 external control in relapsed\/refractory follicular lymphoma","volume":"23","author":"Palomba","year":"2023","journal-title":"Expert Rev. Anticancer. Ther."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"100992","DOI":"10.1016\/j.blre.2022.100992","article-title":"Follicular lymphoma: The long and winding road leading to your cure?","volume":"57","author":"Gordon","year":"2023","journal-title":"Blood Rev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1001\/jamainternmed.2023.0190","article-title":"Clinical Trials Portfolio and Regulatory History of Idelalisib in Indolent Non-Hodgkin Lymphoma: A Systematic Review and Meta-analysis","volume":"183","author":"Banerjee","year":"2023","journal-title":"JAMA Intern. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"99","DOI":"10.2147\/BLCTT.S282247","article-title":"A Promising Future for Precision Epigenetic Therapy for Follicular and Diffuse Large B-Cell Lymphoma?","volume":"12","author":"Chung","year":"2022","journal-title":"Blood Lymphat. Cancer Targets Ther."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e836","DOI":"10.1097\/HS9.0000000000000836","article-title":"Lenalidomide Consolidation Added to Rituximab Maintenance Therapy in Patients Remaining PET Positive After Treatment for Relapsed Follicular Lymphoma: A Phase 2 Australasian Leukaemia & Lymphoma Group NHL26 Study","volume":"7","author":"Trotman","year":"2023","journal-title":"HemaSphere"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3239","DOI":"10.1200\/JCO.22.00843","article-title":"Six-Year Results from RELEVANCE: Lenalidomide Plus Rituximab (R2) Versus Rituximab-Chemotherapy Followed by Rituximab Maintenance in Untreated Advanced Follicular Lymphoma","volume":"40","author":"Morschhauser","year":"2022","journal-title":"J. Clin. Oncol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"122","DOI":"10.56875\/2589-0646.1047","article-title":"Understanding the etiology of pancytopenias in the CAR T-cell therapy setting: What we know and what we don\u2019t?","volume":"15","author":"Yassine","year":"2022","journal-title":"Hematol.\/Oncol. Stem Cell Ther."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Rodgers, T.D., and Barr, P.M. (2023, May 15). Management of relapsed follicular lymphoma. Annals of Lymphoma, North America, 5 April 2021. Available online: https:\/\/aol.amegroups.com\/article\/view\/7195.","DOI":"10.21037\/aol-21-1"},{"key":"ref_17","unstructured":"(2023, May 15). Obinutuzumab. Available online: https:\/\/www.gazzettaufficiale.it\/eli\/gu\/2019\/03\/18\/65\/sg\/pdf."},{"key":"ref_18","unstructured":"(2023, May 15). Idelalisib. Available online: https:\/\/www.gazzettaufficiale.it\/eli\/gu\/2015\/01\/02\/1\/sg\/pdf."},{"key":"ref_19","unstructured":"(2023, May 15). Lenalidomide. Available online: https:\/\/www.gazzettaufficiale.it\/eli\/gu\/2021\/02\/20\/43\/sg\/pdf."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1007\/s40273-021-01052-3","article-title":"Lifetime Costs for Treated Follicular Lymphoma Patients in the US","volume":"39","author":"Eichten","year":"2021","journal-title":"PharmacoEconomics"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1176","DOI":"10.1016\/j.jval.2018.03.007","article-title":"A Generic Model for Follicular Lymphoma: Predicting Cost, Life Expectancy, and Quality-Adjusted-Life-Year Using UK Population\u2013Based Observational Data","volume":"21","author":"Wang","year":"2018","journal-title":"Value Health"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1016\/j.clinthera.2012.02.019","article-title":"Economic Evaluation of Sequential Treatments for Follicular Non-Hodgkin Lymphoma","volume":"34","author":"Soini","year":"2012","journal-title":"Clin. Ther."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Breccia, M., Chiodi, F., Nardozza, A.P., Valsecchi, D., Perrone, V., Sangiorgi, D., Giacomini, E., Rendace, M.C., Coco, P., and Premoli, E. (2022). Real-World Analysis of the Therapeutic Management and Disease Burden in Chronic Myeloid Leukemia Patients with Later Lines in Italy. J. Clin. Med., 11.","DOI":"10.3390\/jcm11133597"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/0021-9681(87)90171-8","article-title":"A new method of classifying prognostic comorbidity in longitudinal studies: Development and validation","volume":"40","author":"Charlson","year":"1987","journal-title":"J. Chronic Dis."},{"key":"ref_25","unstructured":"(2023, March 03). Istituto Nazionale di Statistica (ISTAT). Available online: https:\/\/www.istat.it."},{"key":"ref_26","unstructured":"GLOBOCAN (2023, March 03). Cancer Today. Available online: https:\/\/gco.iarc.fr\/today\/home."},{"key":"ref_27","unstructured":"SEER (2023, March 03). Cancer Stat Facts, Available online: https:\/\/seer.cancer.gov\/statfacts\/index.html."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1007\/s10552-019-01155-5","article-title":"Global patterns and trends in the incidence of non-Hodgkin lymphoma","volume":"30","author":"Znaor","year":"2019","journal-title":"Cancer Causes Control."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1038\/s41408-020-00340-z","article-title":"Follicular lymphoma in the modern era: Survival, treatment outcomes, and identification of high-risk subgroups","volume":"10","author":"Batlevi","year":"2020","journal-title":"Blood Cancer J."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e289","DOI":"10.1016\/S2352-3026(22)00033-3","article-title":"Treatment patterns and outcomes of patients with relapsed or refractory follicular lymphoma receiving three or more lines of systemic therapy (LEO CReWE): A multicentre cohort study","volume":"9","author":"Casulo","year":"2022","journal-title":"Lancet Haematol."},{"key":"ref_31","first-page":"148","article-title":"Treatment Patterns and Health Care Costs in Commercially Insured Patients with Follicular Lymphoma","volume":"7","author":"Fowler","year":"2020","journal-title":"J. Health Econ. Outcomes Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1038\/s41408-020-0299-0","article-title":"Patterns of change in treatment, response, and outcome in patients with follicular lymphoma over the last four decades: A single-center experience","volume":"10","author":"Mozas","year":"2020","journal-title":"Blood Cancer J."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e19557","DOI":"10.1200\/jco.2014.32.15_suppl.e19557","article-title":"Treatment patterns, mortality, and health care utilization and costs in indolent non-Hodgkin lymphoma patients with relapsed or refractory disease","volume":"32","author":"Meyer","year":"2014","journal-title":"J. Clin. Oncol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Kanters, S., Ball, G., Kahl, B., Wiesinger, A., Limbrick-Oldfield, E.H., Sudhindra, A., Snider, J.T., and Patel, A.R. (2023). Clinical outcomes in patients relapsed\/refractory after \u22652 prior lines of therapy for follicular lymphoma: A systematic literature review and meta-analysis. BMC Cancer, 23.","DOI":"10.1186\/s12885-023-10546-6"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1111\/bjh.18640","article-title":"Long-term follow-up demonstrates curative potential of autologous stem cell transplantation for relapsed follicular lymphoma","volume":"201","author":"Puckrin","year":"2023","journal-title":"Br. J. Haematol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"393","DOI":"10.2217\/cer-2018-0094","article-title":"Economic burden and treatment patterns for patients with diffuse large B-cell lymphoma and follicular lymphoma in the USA","volume":"8","author":"Ren","year":"2019","journal-title":"J. Comp. Eff. Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"657","DOI":"10.2165\/11314820-000000000-00000","article-title":"Economic Burden of Follicular Non-Hodgkin\u2019s Lymphoma","volume":"27","author":"Foster","year":"2009","journal-title":"PharmacoEconomics"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"41","DOI":"10.3310\/hta13suppl2-06","article-title":"Rituximab for the treatment of relapsed or refractory stage III or IV follicular non-Hodgkin\u2019s lymphoma","volume":"13","author":"Boland","year":"2009","journal-title":"Health Technol. Assess."},{"key":"ref_39","unstructured":"(2023, March 03). Available online: https:\/\/www.aiom.it\/wp-content\/uploads\/2018\/11\/2018_LG_AIOM_Linfomi.pdf."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1080\/13696998.2019.1702990","article-title":"Real-world costs of illness of Hodgkin and the main B-Cell Non-Hodgkin lymphomas in France","volume":"23","author":"Costa","year":"2020","journal-title":"J. Med. Econ."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/15\/17\/4403\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:45:34Z","timestamp":1760129134000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/15\/17\/4403"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,2]]},"references-count":40,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2023,9]]}},"alternative-id":["cancers15174403"],"URL":"https:\/\/doi.org\/10.3390\/cancers15174403","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,2]]}}}