{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T02:45:29Z","timestamp":1771987529686,"version":"3.50.1"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,2,20]],"date-time":"2024-02-20T00:00:00Z","timestamp":1708387200000},"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>Targeted chemotherapy and immune checkpoint inhibitors (ICPi) have expanded the spectrum of therapies for patients with relapsed\/refractory (r\/r) Hodgkin\u2019s disease and significantly improved the proportion of patients with long-term disease control. However, there is no standardized therapeutic option in case of further progression. Recently, we demonstrated that therapy with MEPED (metronomic chemotherapy, everolimus, pioglitazone, etoricoxib, dexamethasone) is highly effective in patients with r\/r Hodgkin\u2019s disease. The benefit after pre-treatment with ICPi has not been studied, yet. Here, we report a patient with progressive Hodgkin\u2019s disease on Pembrolizumab for the first time who achieved sustained complete remission (CR) after initiation of MEPED therapy. A 57-year-old patient was pre-treated with brentuximab vedotin for relapsed advanced Hodgkin\u2019s disease and had received Pembrolizumab for progression from November 2020 to July 2022. Due to further progression, MEPED therapy was started in August 2022 and continued until May 2023. It consisted of a strictly oral daily (28-day cycle) application of low-dose treosulfan 250\u00a0mg, everolimus 15\u00a0mg, pioglitazone 45\u00a0mg, etoricoxib 60\u00a0mg, and dexamethasone 0.5\u00a0mg. Treatment response was evaluated by F-18 FDG-PET\/CT (PET\/CT). CR was defined by a negative Deauville score (DS) of 1-3. Already 3\u00a0months after starting MEPED, a CR (DS: 3) was confirmed by PET\/CT in November 2022. The next follow-up in May 2023 continued to show CR (DS: 3). The therapy was very well tolerated. No hematological or other organ toxicity was observed. However, in May 2023 the patient presented with leg edema and weight gain, most likely due to pioglitazone and the PET\/CT revealed suspected everolimus-induced pneumonitis, so MEPED was discontinued and diuretic therapy and treatment with prednisolone was started with gradual dose reduction. This resulted in a rapid complete resolution of the symptoms. The next PET-CT in July 2023 continued to show CR (DS: 3) without evidence of pneumonitis. Currently, therapy with MEPED has not been resumed. In conclusion, we demonstrate for the first time that MEPED therapy is highly effective in a patient with Hodgkin\u2019s disease who has been refractory to ICPi. Sustained CR was achieved over 11\u00a0months after initiation of MEPED therapy. Further studies on a larger patient cohort should be performed.<\/jats:p>","DOI":"10.3389\/fphar.2024.1334233","type":"journal-article","created":{"date-parts":[[2024,2,20]],"date-time":"2024-02-20T05:58:23Z","timestamp":1708408703000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Case report: Sustained complete remission with all-oral MEPED therapy in a patient with Hodgkin\u2019s disease developing resistance to pembrolizumab"],"prefix":"10.3389","volume":"15","author":[{"given":"K.","family":"Reuthner","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P.","family":"Aubele","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K.","family":"Menhart","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P.","family":"Rath","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D. 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