{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T09:25:11Z","timestamp":1790673911585,"version":"4.1.0"},"reference-count":32,"publisher":"American Society of Hematology","issue":"5","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,2,1]]},"abstract":"<jats:sec>\n                  <jats:title>Abstract<\/jats:title>\n                  <jats:p>Extranodal marginal zone lymphoma (EMZL) has a very indolent course, and the validation of surrogate markers could accelerate novel therapies. Although prognostic markers do exist, no surrogate markers have been validated in EMZL. We hypothesized that time to complete response within 24 months (TTCR24) and complete response (CR) at 24 months (CR24) could be valid surrogate markers of progression-free survival (PFS). The International Extranodal Lymphoma Study Group 19 phase 3 trial showed the advantage of double therapy (rituximab\u00a0+ chlorambucil) over single therapy (rituximab or chlorambucil) on PFS. We used 2 recently published single-trial approaches to assess whether TTCR24 and CR24 were good surrogate markers of 8-year PFS (8y-PFS). Among the 401 patients, 264 (66%) reached a CR in the first 24 months, of which 222 (84%) remained in CR at month 24. The cumulative incidence of CR over time was significantly higher in patients under double therapy (hazard ratio, 1.75; P\u00a0&amp;lt; .001). The double therapy arm was associated with a higher CR24 rate, a shorter TTCR24, and a longer 8y-PFS. The estimated proportion of treatment effect on 8y-PFS explained by TTCR24 was 95% (95% confidence interval [CI], 0.27-1.87). CR24 was also a strong surrogate marker because it mediated 90% (95% CI, 0.51-2.22) of the treatment effect on PFS and its natural indirect effect was significant throughout the follow-up. We found that TTCR24 predicted 95% and that CR24 mediated 90% of the treatment effect on long-term PFS. Therefore, TTCR24 and CR24 could be used in clinical trials as informative and valid early indicators of treatment effect on PFS. This trial was registered at www.clinicaltrials.gov as #NCT00210353.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1182\/blood.2023020984","type":"journal-article","created":{"date-parts":[[2023,10,6]],"date-time":"2023-10-06T21:00:58Z","timestamp":1696626058000},"page":"422-428","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":14,"title":["Early complete response as a validated surrogate marker in extranodal marginal zone lymphoma systemic therapy"],"prefix":"10.1182","volume":"143","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5695-911X","authenticated-orcid":false,"given":"C\u00f4me","family":"Bommier","sequence":"first","affiliation":[{"name":"1INSERM U1153, Epidemiology and Clinical Statistics for Trials & Real-world Evidence Research Team, Saint-Louis Hospital, Paris, France"},{"name":"2Universit\u00e9 Paris Cit\u00e9, Paris, France"},{"name":"3Department of Hemato-Oncology, Saint-Louis Hospital, Assistance Publique\u2013H\u00f4pitaux de Paris, D\u00e9partement M\u00e9dico Universitaire H\u00e9matologie et Immunologie, Paris, France"},{"name":"4Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5522-6109","authenticated-orcid":false,"given":"Emanuele","family":"Zucca","sequence":"additional","affiliation":[{"name":"5Oncology Institute of Southern Switzerland, Ente Ospedaliero Cantonale, Bellinzona, Switzerland"},{"name":"6Institute of Oncology Research, Bellinzona, Switzerland"},{"name":"7Faculty of Biomedical Sciences, Universit\u00e0 della Svizzera Italiana, Lugano, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvie","family":"Chevret","sequence":"additional","affiliation":[{"name":"1INSERM U1153, Epidemiology and Clinical Statistics for Trials & Real-world Evidence Research Team, Saint-Louis Hospital, Paris, France"},{"name":"8Biostatistics and Medical Information Department, Saint-Louis Hospital, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annarita","family":"Conconi","sequence":"additional","affiliation":[{"name":"9Struttura Semplice a Valenza Dipartimentale di Ematologia, Ospedale degli Infermi, Azienda Sanitaria Locale di Biella, Ponderano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grzegorz","family":"Nowakowski","sequence":"additional","affiliation":[{"name":"10Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1867-0526","authenticated-orcid":false,"given":"Matthew J.","family":"Maurer","sequence":"additional","affiliation":[{"name":"4Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7482-178X","authenticated-orcid":false,"given":"James R.","family":"Cerhan","sequence":"additional","affiliation":[{"name":"4Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Thieblemont","sequence":"additional","affiliation":[{"name":"2Universit\u00e9 Paris Cit\u00e9, Paris, France"},{"name":"3Department of Hemato-Oncology, Saint-Louis Hospital, Assistance Publique\u2013H\u00f4pitaux de Paris, D\u00e9partement M\u00e9dico Universitaire H\u00e9matologie et Immunologie, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00e9r\u00f4me","family":"Lambert","sequence":"additional","affiliation":[{"name":"1INSERM U1153, Epidemiology and Clinical Statistics for Trials & Real-world Evidence Research Team, Saint-Louis Hospital, Paris, 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