Biomodulatory Treatment Regimen, MEPED, Rescues Relapsed and Refractory Classic Hodgkin’s Disease

Introduction: Current combined intensive chemotherapy and radiation regimens yield excellent survival rates in advanced classic Hodgkin’s lymphoma (cHL). However, acute toxicity in elderly, comorbid patients can be challenging and long-term survival in refractory patients remains poor. Patients and...

Descripción completa

Detalles Bibliográficos
Autores principales: Lüke, Florian, Harrer, Dennis C., Menhart, Karin, Wolff, Daniel, Holler, Ernst, Hellwig, Dirk, Herr, Wolfgang, Grube, Matthias, Vogelhuber, Martin, Reichle, Albrecht, Heudobler, Daniel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8249731/
https://www.ncbi.nlm.nih.gov/pubmed/34220492
http://dx.doi.org/10.3389/fphar.2021.599561
_version_ 1783716957397188608
author Lüke, Florian
Harrer, Dennis C.
Menhart, Karin
Wolff, Daniel
Holler, Ernst
Hellwig, Dirk
Herr, Wolfgang
Grube, Matthias
Vogelhuber, Martin
Reichle, Albrecht
Heudobler, Daniel
author_facet Lüke, Florian
Harrer, Dennis C.
Menhart, Karin
Wolff, Daniel
Holler, Ernst
Hellwig, Dirk
Herr, Wolfgang
Grube, Matthias
Vogelhuber, Martin
Reichle, Albrecht
Heudobler, Daniel
author_sort Lüke, Florian
collection PubMed
description Introduction: Current combined intensive chemotherapy and radiation regimens yield excellent survival rates in advanced classic Hodgkin’s lymphoma (cHL). However, acute toxicity in elderly, comorbid patients can be challenging and long-term survival in refractory patients remains poor. Patients and Methods: 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 mg p.o. daily, everolimus 15 mg p.o. daily to achieve serum trough levels of 15 ng/ml, pioglitazone 45 mg p.o. daily, etoricoxib 60 mg p.o. daily and dexamethasone 0.5 mg 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 mg 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. (18)F-fluoro-2-deoxy-d-glucose positron emission tomography combined with computed tomography scan (FDG-PET/CT) was performed to monitor treatment and follow-up. Results: In the three newly treated patients, CT scans showed partial remissions after 2–5 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 >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 days. All three previously published patients received allo HSCT for consolidation and have achieved cCR. Conclusions: 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.
format Online
Article
Text
id pubmed-8249731
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-82497312021-07-03 Biomodulatory Treatment Regimen, MEPED, Rescues Relapsed and Refractory Classic Hodgkin’s Disease Lüke, Florian Harrer, Dennis C. Menhart, Karin Wolff, Daniel Holler, Ernst Hellwig, Dirk Herr, Wolfgang Grube, Matthias Vogelhuber, Martin Reichle, Albrecht Heudobler, Daniel Front Pharmacol Pharmacology Introduction: Current combined intensive chemotherapy and radiation regimens yield excellent survival rates in advanced classic Hodgkin’s lymphoma (cHL). However, acute toxicity in elderly, comorbid patients can be challenging and long-term survival in refractory patients remains poor. Patients and Methods: 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 mg p.o. daily, everolimus 15 mg p.o. daily to achieve serum trough levels of 15 ng/ml, pioglitazone 45 mg p.o. daily, etoricoxib 60 mg p.o. daily and dexamethasone 0.5 mg 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 mg 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. (18)F-fluoro-2-deoxy-d-glucose positron emission tomography combined with computed tomography scan (FDG-PET/CT) was performed to monitor treatment and follow-up. Results: In the three newly treated patients, CT scans showed partial remissions after 2–5 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 >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 days. All three previously published patients received allo HSCT for consolidation and have achieved cCR. Conclusions: 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. Frontiers Media S.A. 2021-06-18 /pmc/articles/PMC8249731/ /pubmed/34220492 http://dx.doi.org/10.3389/fphar.2021.599561 Text en Copyright © 2021 Lüke, Harrer, Menhart, Wolff, Holler, Hellwig, Herr, Grube, Vogelhuber, Reichle and Heudobler. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Lüke, Florian
Harrer, Dennis C.
Menhart, Karin
Wolff, Daniel
Holler, Ernst
Hellwig, Dirk
Herr, Wolfgang
Grube, Matthias
Vogelhuber, Martin
Reichle, Albrecht
Heudobler, Daniel
Biomodulatory Treatment Regimen, MEPED, Rescues Relapsed and Refractory Classic Hodgkin’s Disease
title Biomodulatory Treatment Regimen, MEPED, Rescues Relapsed and Refractory Classic Hodgkin’s Disease
title_full Biomodulatory Treatment Regimen, MEPED, Rescues Relapsed and Refractory Classic Hodgkin’s Disease
title_fullStr Biomodulatory Treatment Regimen, MEPED, Rescues Relapsed and Refractory Classic Hodgkin’s Disease
title_full_unstemmed Biomodulatory Treatment Regimen, MEPED, Rescues Relapsed and Refractory Classic Hodgkin’s Disease
title_short Biomodulatory Treatment Regimen, MEPED, Rescues Relapsed and Refractory Classic Hodgkin’s Disease
title_sort biomodulatory treatment regimen, meped, rescues relapsed and refractory classic hodgkin’s disease
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8249731/
https://www.ncbi.nlm.nih.gov/pubmed/34220492
http://dx.doi.org/10.3389/fphar.2021.599561
work_keys_str_mv AT lukeflorian biomodulatorytreatmentregimenmepedrescuesrelapsedandrefractoryclassichodgkinsdisease
AT harrerdennisc biomodulatorytreatmentregimenmepedrescuesrelapsedandrefractoryclassichodgkinsdisease
AT menhartkarin biomodulatorytreatmentregimenmepedrescuesrelapsedandrefractoryclassichodgkinsdisease
AT wolffdaniel biomodulatorytreatmentregimenmepedrescuesrelapsedandrefractoryclassichodgkinsdisease
AT hollerernst biomodulatorytreatmentregimenmepedrescuesrelapsedandrefractoryclassichodgkinsdisease
AT hellwigdirk biomodulatorytreatmentregimenmepedrescuesrelapsedandrefractoryclassichodgkinsdisease
AT herrwolfgang biomodulatorytreatmentregimenmepedrescuesrelapsedandrefractoryclassichodgkinsdisease
AT grubematthias biomodulatorytreatmentregimenmepedrescuesrelapsedandrefractoryclassichodgkinsdisease
AT vogelhubermartin biomodulatorytreatmentregimenmepedrescuesrelapsedandrefractoryclassichodgkinsdisease
AT reichlealbrecht biomodulatorytreatmentregimenmepedrescuesrelapsedandrefractoryclassichodgkinsdisease
AT heudoblerdaniel biomodulatorytreatmentregimenmepedrescuesrelapsedandrefractoryclassichodgkinsdisease