{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T02:45:39Z","timestamp":1771987539972,"version":"3.50.1"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,6,18]],"date-time":"2021-06-18T00:00:00Z","timestamp":1623974400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p><jats:bold>Introduction:<\/jats:bold> Current combined intensive chemotherapy and radiation regimens yield excellent survival rates in advanced classic Hodgkin\u2019s lymphoma (cHL). However, acute toxicity in elderly, comorbid patients can be challenging and long-term survival in refractory patients remains poor.<\/jats:p><jats:p><jats:bold>Patients and Methods:<\/jats:bold> We report on six patients with r\/r HL, three patients with long-term follow-up, three newly treated, after biomodulatory therapy. All patients received MEPED (treosulfan 250\u00a0mg p.o. daily, everolimus 15\u00a0mg p.o. daily to achieve serum trough levels of 15\u00a0ng\/ml, pioglitazone 45\u00a0mg p.o. daily, etoricoxib 60\u00a0mg p.o. daily and dexamethasone 0.5\u00a0mg p.o. daily). Patients had either received every at that time approved systemic treatment or were ineligible for standard treatment, including immune checkpoint inhibition (ICPi) due to prior demyelinating autoimmune polyneuropathy, myasthenia gravis and previous allogeneic hematopoietic-stem-cell transplant (alloHSCT). Medication was administered continuously from day 1. One patient with relapse after alloHSCT received trofosfamide 50\u00a0mg daily instead of treosulfan to avoid risk of increased myelotoxicity. The patients were treated in individual healing attempts outside a clinical trial after institutional review board approval. <jats:sup>18<\/jats:sup>F-fluoro-2-deoxy-<jats:sc>d<\/jats:sc>-glucose positron emission tomography combined with computed tomography scan (FDG-PET\/CT) was performed to monitor treatment and follow-up.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> In the three newly treated patients, CT scans showed partial remissions after 2\u20135 months on MEPED treatment. Two patients had achieved PET Deauville score 2 and 3, while the third remained positive at Deauville score 5. One patient achieving PR became eligible for alloHSCT, while the other two patients continued treatment with MEPED. All patients eventually achieved continuous complete remission (cCR), one after consecutive alloHSCT, one after discontinuing MEPED consolidation for &amp;gt;1 year and one on on-going MEPED consolidation, respectively. Only one patient experienced Grade 3 toxicity (bacterial pneumonia) requiring temporary discontinuation of MEPED for 10\u00a0days. All three previously published patients received allo HSCT for consolidation and have achieved cCR.<\/jats:p><jats:p><jats:bold>Conclusions:<\/jats:bold> MEPED is well tolerated with low toxicity and highly efficacious in relapsed\/refractory cHL, including severely comorbid patients. Due to its immunomodulatory components, MEPED might also have a synergistic potential when combined with ICPi but requires further evaluation within a clinical trial.<\/jats:p>","DOI":"10.3389\/fphar.2021.599561","type":"journal-article","created":{"date-parts":[[2021,6,18]],"date-time":"2021-06-18T04:45:46Z","timestamp":1623991546000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":15,"title":["Biomodulatory Treatment Regimen, MEPED, Rescues Relapsed and Refractory Classic Hodgkin\u2019s Disease"],"prefix":"10.3389","volume":"12","author":[{"given":"Florian","family":"L\u00fcke","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dennis C.","family":"Harrer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karin","family":"Menhart","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Wolff","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ernst","family":"Holler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dirk","family":"Hellwig","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wolfgang","family":"Herr","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthias","family":"Grube","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Vogelhuber","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Albrecht","family":"Reichle","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Heudobler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,6,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"3431","DOI":"10.1200\/JCO.2003.07.131","article-title":"Long-Term Cause-specific Mortality of Patients Treated for Hodgkin's Disease","volume":"21","author":"Aleman","year":"2003","journal-title":"J Clin Oncol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"665","DOI":"10.1023\/a:1008396525292","article-title":"High-dose BEAM Chemotherapy with Autologous Peripheral Blood Progenitor-Cell Transplantation for Unselected Patients with Primary Refractory or Relapsed Hodgkin's Disease","volume":"11","author":"Argiris","year":"2000","journal-title":"Ann. 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