{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T15:14:08Z","timestamp":1778253248858,"version":"3.51.4"},"reference-count":30,"publisher":"BMJ","issue":"5","license":[{"start":{"date-parts":[[2022,5,11]],"date-time":"2022-05-11T00:00:00Z","timestamp":1652227200000},"content-version":"unspecified","delay-in-days":10,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"U.S. Department of Health and Human Services > National Institutes of Health > National Cancer Institute","award":["R21 CA259236-01"],"award-info":[{"award-number":["R21 CA259236-01"]}]},{"DOI":"10.13039\/100000871","name":"Mayo Clinic","doi-asserted-by":"publisher","award":["Lawrence W. and Marilyn W. Matteson Award"],"award-info":[{"award-number":["Lawrence W. and Marilyn W. Matteson Award"]}],"id":[{"id":"10.13039\/100000871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2022,4,24]]},"published-print":{"date-parts":[[2022,5]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Patients with metastatic melanoma rely on PD-(L)1 immunotherapy, but only one-third of patients experience treatment response and all initial responders eventually develop resistance. Tumour-derived extracellular vesicles expressing Programmed death ligand 1 (evPD-L1) and soluble Programmed death ligand 1 (sPD-L1) in peripheral blood of patients with melanoma limit PD-(L)1 immunotherapy and correlate with poor survival. Therapeutic plasma exchange (TPE) removes immunosuppressive evPD-L1 and sPD-L1. We hypothesise that TPE may rescue and restore antimelanoma immunity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this two-arm study, 60 patients with metastatic melanoma progressing on checkpoint inhibition will be accrued. All patients will undergo radiotherapy on days 1\u20135 (at least one measurable lesion will not be irradiated) and ongoing checkpoint inhibition on day 8 and every 2\u20133 weeks per standard of care. Patients with baseline sPD-L1 level of \u22651.7\u2009ng\/mL and adequate clinical capacity will be enrolled in the TPE intervention arm and will undergo TPE on days 5\u20137, in addition to standard of care radiotherapy and immunotherapy. Other patients will remain in the standard of care arm.<\/jats:p>\n                    <jats:p>\n                      The primary endpoint of the study is to evaluate safety. Secondary endpoints include kinetics of sPD-L1 and evPD-L1 and clinical response by RECIST (Response Evaluation Criteria in Solid Tumors) criteria. Study registered at ClinicalTrials.gov (\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT04581382\">NCT04581382<\/jats:ext-link>\n                      ).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>This trial has been approved by the Mayo Clinic Institutional Review Board. It will assess the safety and feasibility of TPE in improving outcomes for PD-(L)1 inhibitor immunotherapy in melanoma. Data will be maintained on a secure database with deidentified patient information. Data will be shared on publication in a peer-reviewed journal without the aid of professional writers. If successful, this trial will lay the ground for phase II studies that will include cancer treated with PD-(L)1 inhibitors which may benefit from TPE such as renal, bladder and lung cancers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT04581382\">NCT04581382<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2021-050112","type":"journal-article","created":{"date-parts":[[2022,5,17]],"date-time":"2022-05-17T06:49:50Z","timestamp":1652770190000},"page":"e050112","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":11,"title":["Rescuing Cancer Immunity by Plasma Exchange in Metastatic Melanoma (ReCIPE-M1): protocol for a single-institution, open-label safety trial of plasma exchange to clear sPD-L1 for immunotherapy"],"prefix":"10.1136","volume":"12","clinical-trial-number":[{"clinical-trial-number":"nct04581382","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct04581382","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Tara M","family":"Davidson","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nathan","family":"Foster","sequence":"additional","affiliation":[{"name":"Department of Quantitative Health Sciences, Mayo Clinic, Rochester, Minnesota, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabrice","family":"Lucien","sequence":"additional","affiliation":[{"name":"Department of Urology, Mayo Clinic, Rochester, Minnesota, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Svetomir","family":"Markovic","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Mayo Clinic, Rochester, Minnesota, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haidong","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Urology, Mayo Clinic, Rochester, Minnesota, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey L","family":"Winters","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Mayo Clinic, Rochester, Minnesota, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sean S","family":"Park","sequence":"additional","affiliation":[{"name":"Radiation Oncology, Mayo Clinic, Rochester, Minnesota, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0319-0239","authenticated-orcid":false,"given":"Jacob J","family":"Orme","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Mayo Clinic, Rochester, Minnesota, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2022,5,12]]},"reference":[{"key":"2025121422220789000_12.5.e050112.1","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1200\/JCO.1986.4.6.900","article-title":"Alpha-2 interferon therapy of hairy-cell leukemia: a multicenter study of 64 patients","volume":"4","author":"Golomb","year":"1986","journal-title":"J Clin Oncol"},{"key":"2025121422220789000_12.5.e050112.2","unstructured":"Dighe S . 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