IL6-receptor antibody tocilizumab as salvage therapy in severe chronic graft-versus-host disease after allogeneic hematopoietic stem cell transplantation: a retrospective analysis
Identifieur interne : 000350 ( Main/Exploration ); précédent : 000349; suivant : 000351IL6-receptor antibody tocilizumab as salvage therapy in severe chronic graft-versus-host disease after allogeneic hematopoietic stem cell transplantation: a retrospective analysis
Auteurs : Anna-Sophia Kattner ; Ernst Holler ; Barbara Holler ; Sebastian Klobuch ; Daniela Weber ; Danilo Martinovic ; Matthias Edinger ; Wolfgang Herr ; Daniel WolffSource :
- Annals of Hematology [ 0939-5555 ] ; 2020.
Descripteurs français
- KwdFr :
- Adulte, Adulte d'âge moyen, Anticorps monoclonaux humanisés (usage thérapeutique), Femelle, Humains, Immunosuppresseurs (usage thérapeutique), Interleukine-6 (antagonistes et inhibiteurs), Maladie chronique, Maladie du greffon contre l'hôte (traitement médicamenteux), Maladie du greffon contre l'hôte (étiologie), Mâle, Récidive, Résultat thérapeutique, Sepsie (étiologie), Thérapie de rattrapage (), Transplantation de cellules souches hématopoïétiques (effets indésirables), Transplantation homologue, Études de suivi, Études rétrospectives.
- MESH :
- antagonistes et inhibiteurs : Interleukine-6.
- effets indésirables : Transplantation de cellules souches hématopoïétiques.
- traitement médicamenteux : Maladie du greffon contre l'hôte.
- usage thérapeutique : Anticorps monoclonaux humanisés, Immunosuppresseurs.
- étiologie : Maladie du greffon contre l'hôte, Sepsie.
- Adulte, Adulte d'âge moyen, Femelle, Humains, Maladie chronique, Mâle, Récidive, Résultat thérapeutique, Thérapie de rattrapage, Transplantation homologue, Études de suivi, Études rétrospectives.
English descriptors
- KwdEn :
- Adult, Antibodies, Monoclonal, Humanized (therapeutic use), Chronic Disease, Female, Follow-Up Studies, Graft vs Host Disease (drug therapy), Graft vs Host Disease (etiology), Hematopoietic Stem Cell Transplantation (adverse effects), Humans, Immunosuppressive Agents (therapeutic use), Interleukin-6 (antagonists & inhibitors), Male, Middle Aged, Recurrence, Retrospective Studies, Salvage Therapy (methods), Sepsis (etiology), Transplantation, Homologous, Treatment Outcome.
- MESH :
- chemical , antagonists & inhibitors : Interleukin-6.
- chemical , therapeutic use : Antibodies, Monoclonal, Humanized, Immunosuppressive Agents.
- adverse effects : Hematopoietic Stem Cell Transplantation.
- drug therapy : Graft vs Host Disease.
- etiology : Graft vs Host Disease, Sepsis.
- methods : Salvage Therapy.
- Adult, Chronic Disease, Female, Follow-Up Studies, Humans, Male, Middle Aged, Recurrence, Retrospective Studies, Transplantation, Homologous, Treatment Outcome.
Abstract
Chronic graft-versus-host disease (cGvHD) remains the most relevant factor affecting survival after allogeneic hematopoietic stem cell transplantation (alloHSCT). Besides corticosteroids (and ibrutinib in the USA), there is no established therapy for cGvHD. Tocilizumab, a humanized IgG1 IL6-receptor antibody, has shown efficacy in acute GvHD and cGvHD. We retrospectively analyzed the efficacy and safety of tocilizumab for the treatment of advanced cGvHD. Eleven patients with severe steroid refractory cGvHD (median age 49; range 21–62 years) that received at least two prior lines of therapy for cGvHD (range 2–8 regimens) were treated with tocilizumab (q4w, dosage 8 mg/kg IV) with a median number of 15 cycles (range 2–31). NIH consensus criteria grading for cGvHD were recorded prior to tocilizumab administration and after 3, 6, and 12 months of therapy. All patients received additional concomitant immunosuppression (IS) but no new IS within the last 4 weeks before start of tocilizumab and response assessment was terminated before start of any new IS. The median number of days between alloHSCT and initiation of tocilizumab therapy was 1033 days. Organs involved at initiation of tocilizumab therapy were skin (100%, all grade 3), eyes (82%), fascia (82%), mouth (64%), lungs (55%), and genitals (18%). Overall, 7/10 patients (70%) showed partial remission, 2/10 patients (20%) showed progressive cGvHD, 1/10 patient (10%) showed mixed response, and 1 patient died due to sepsis before first response assessment 1.5 months after initiation of treatment. Four patients required subsequent new immunosuppressive treatment. Two patients developed bacterial sepsis, one of whom died. The overall survival and relapse-free survival were 82% with an average follow-up of 22 months (range 1.5–52 months). Tocilizumab seems a promising treatment option in advanced cGvHD but further evaluation within a phase II trial is required.
Url:
DOI: 10.1007/s00277-020-03968-w
PubMed: 32086584
PubMed Central: 7069928
Affiliations:
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analysis</title><author><name sortKey="Kattner, Anna Sophia" sort="Kattner, Anna Sophia" uniqKey="Kattner A" first="Anna-Sophia" last="Kattner">Anna-Sophia Kattner</name><affiliation><nlm:aff id="Aff1"></nlm:aff></affiliation></author><author><name sortKey="Holler, Ernst" sort="Holler, Ernst" uniqKey="Holler E" first="Ernst" last="Holler">Ernst Holler</name><affiliation><nlm:aff id="Aff1"></nlm:aff></affiliation></author><author><name sortKey="Holler, Barbara" sort="Holler, Barbara" uniqKey="Holler B" first="Barbara" last="Holler">Barbara Holler</name><affiliation><nlm:aff id="Aff1"></nlm:aff></affiliation></author><author><name sortKey="Klobuch, Sebastian" sort="Klobuch, Sebastian" uniqKey="Klobuch S" first="Sebastian" last="Klobuch">Sebastian Klobuch</name><affiliation><nlm:aff id="Aff1"></nlm:aff></affiliation></author><author><name sortKey="Weber, Daniela" sort="Weber, Daniela" uniqKey="Weber D" first="Daniela" last="Weber">Daniela Weber</name><affiliation><nlm:aff id="Aff1"></nlm:aff></affiliation></author><author><name sortKey="Martinovic, Danilo" sort="Martinovic, Danilo" uniqKey="Martinovic D" first="Danilo" last="Martinovic">Danilo Martinovic</name><affiliation><nlm:aff id="Aff1"></nlm:aff></affiliation></author><author><name sortKey="Edinger, Matthias" sort="Edinger, Matthias" uniqKey="Edinger M" first="Matthias" last="Edinger">Matthias Edinger</name><affiliation><nlm:aff id="Aff1"></nlm:aff></affiliation></author><author><name sortKey="Herr, Wolfgang" sort="Herr, Wolfgang" uniqKey="Herr W" first="Wolfgang" last="Herr">Wolfgang Herr</name><affiliation><nlm:aff id="Aff1"></nlm:aff></affiliation></author><author><name sortKey="Wolff, Daniel" sort="Wolff, Daniel" uniqKey="Wolff D" first="Daniel" last="Wolff">Daniel Wolff</name><affiliation><nlm:aff id="Aff1"></nlm:aff></affiliation></author></analytic><series><title level="j">Annals of Hematology</title><idno type="ISSN">0939-5555</idno><idno type="eISSN">1432-0584</idno><imprint><date when="2020">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adult</term><term>Antibodies, Monoclonal, Humanized (therapeutic use)</term><term>Chronic Disease</term><term>Female</term><term>Follow-Up Studies</term><term>Graft vs Host Disease (drug therapy)</term><term>Graft vs Host Disease (etiology)</term><term>Hematopoietic Stem Cell Transplantation (adverse effects)</term><term>Humans</term><term>Immunosuppressive Agents (therapeutic use)</term><term>Interleukin-6 (antagonists & inhibitors)</term><term>Male</term><term>Middle Aged</term><term>Recurrence</term><term>Retrospective Studies</term><term>Salvage Therapy (methods)</term><term>Sepsis (etiology)</term><term>Transplantation, Homologous</term><term>Treatment Outcome</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Adulte</term><term>Adulte d'âge moyen</term><term>Anticorps monoclonaux humanisés (usage thérapeutique)</term><term>Femelle</term><term>Humains</term><term>Immunosuppresseurs (usage thérapeutique)</term><term>Interleukine-6 (antagonistes et inhibiteurs)</term><term>Maladie chronique</term><term>Maladie du greffon contre l'hôte (traitement médicamenteux)</term><term>Maladie du greffon contre l'hôte (étiologie)</term><term>Mâle</term><term>Récidive</term><term>Résultat thérapeutique</term><term>Sepsie (étiologie)</term><term>Thérapie de rattrapage ()</term><term>Transplantation de cellules souches hématopoïétiques (effets indésirables)</term><term>Transplantation homologue</term><term>Études de suivi</term><term>Études rétrospectives</term></keywords><keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en"><term>Interleukin-6</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Antibodies, Monoclonal, Humanized</term><term>Immunosuppressive Agents</term></keywords><keywords scheme="MESH" qualifier="adverse effects" xml:lang="en"><term>Hematopoietic Stem Cell Transplantation</term></keywords><keywords scheme="MESH" qualifier="antagonistes et inhibiteurs" xml:lang="fr"><term>Interleukine-6</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Graft vs Host Disease</term></keywords><keywords scheme="MESH" qualifier="effets indésirables" xml:lang="fr"><term>Transplantation de cellules souches hématopoïétiques</term></keywords><keywords scheme="MESH" qualifier="etiology" xml:lang="en"><term>Graft vs Host Disease</term><term>Sepsis</term></keywords><keywords scheme="MESH" qualifier="methods" xml:lang="en"><term>Salvage Therapy</term></keywords><keywords scheme="MESH" qualifier="traitement médicamenteux" xml:lang="fr"><term>Maladie du greffon contre l'hôte</term></keywords><keywords scheme="MESH" qualifier="usage thérapeutique" xml:lang="fr"><term>Anticorps monoclonaux humanisés</term><term>Immunosuppresseurs</term></keywords><keywords scheme="MESH" qualifier="étiologie" xml:lang="fr"><term>Maladie du greffon contre l'hôte</term><term>Sepsie</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Adult</term><term>Chronic Disease</term><term>Female</term><term>Follow-Up Studies</term><term>Humans</term><term>Male</term><term>Middle Aged</term><term>Recurrence</term><term>Retrospective Studies</term><term>Transplantation, Homologous</term><term>Treatment Outcome</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Adulte</term><term>Adulte d'âge moyen</term><term>Femelle</term><term>Humains</term><term>Maladie chronique</term><term>Mâle</term><term>Récidive</term><term>Résultat thérapeutique</term><term>Thérapie de rattrapage</term><term>Transplantation homologue</term><term>Études de suivi</term><term>Études rétrospectives</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="Par1">Chronic graft-versus-host disease (cGvHD) remains the most relevant factor affecting survival after allogeneic hematopoietic stem cell transplantation (alloHSCT). Besides corticosteroids (and ibrutinib in the USA), there is no established therapy for cGvHD. Tocilizumab, a humanized IgG1 IL6-receptor antibody, has shown efficacy in acute GvHD and cGvHD. We retrospectively analyzed the efficacy and safety of tocilizumab for the treatment of advanced cGvHD. Eleven patients with severe steroid refractory cGvHD (median age 49; range 21–62 years) that received at least two prior lines of therapy for cGvHD (range 2–8 regimens) were treated with tocilizumab (q4w, dosage 8 mg/kg IV) with a median number of 15 cycles (range 2–31). NIH consensus criteria grading for cGvHD were recorded prior to tocilizumab administration and after 3, 6, and 12 months of therapy. All patients received additional concomitant immunosuppression (IS) but no new IS within the last 4 weeks before start of tocilizumab and response assessment was terminated before start of any new IS. The median number of days between alloHSCT and initiation of tocilizumab therapy was 1033 days. Organs involved at initiation of tocilizumab therapy were skin (100%, all grade 3), eyes (82%), fascia (82%), mouth (64%), lungs (55%), and genitals (18%). Overall, 7/10 patients (70%) showed partial remission, 2/10 patients (20%) showed progressive cGvHD, 1/10 patient (10%) showed mixed response, and 1 patient died due to sepsis before first response assessment 1.5 months after initiation of treatment. Four patients required subsequent new immunosuppressive treatment. Two patients developed bacterial sepsis, one of whom died. The overall survival and relapse-free survival were 82% with an average follow-up of 22 months (range 1.5–52 months). Tocilizumab seems a promising treatment option in advanced cGvHD but further evaluation within a phase II trial is required.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Socie, G" uniqKey="Socie G">G Socie</name></author><author><name sortKey="Ritz, J" uniqKey="Ritz J">J Ritz</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wolff, D" uniqKey="Wolff D">D Wolff</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Miklos, D" uniqKey="Miklos D">D Miklos</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Martin, Pj" uniqKey="Martin P">PJ Martin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jordan, Sc" uniqKey="Jordan S">SC Jordan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tawara, I" uniqKey="Tawara I">I Tawara</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sheppard, M" uniqKey="Sheppard M">M Sheppard</name></author><author><name sortKey="Laskou, F" uniqKey="Laskou F">F Laskou</name></author><author><name sortKey="Stapleton, Pp" uniqKey="Stapleton P">PP Stapleton</name></author><author><name sortKey="Hadavi, S" uniqKey="Hadavi S">S Hadavi</name></author><author><name sortKey="Dasgupta, B" uniqKey="Dasgupta B">B Dasgupta</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Fleischmann, Rm" uniqKey="Fleischmann R">RM Fleischmann</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="De Benedetti, F" uniqKey="De Benedetti F">F De Benedetti</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Stone, Jh" uniqKey="Stone J">JH Stone</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Le, Rq" uniqKey="Le R">RQ Le</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kennedy, Ga" uniqKey="Kennedy G">GA Kennedy</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jin, H" uniqKey="Jin H">H Jin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Srinivasan, M" uniqKey="Srinivasan M">M Srinivasan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Nakagiri, T" uniqKey="Nakagiri T">T Nakagiri</name></author><author><name sortKey="Inoue, M" uniqKey="Inoue M">M Inoue</name></author><author><name sortKey="Minami, M" uniqKey="Minami M">M Minami</name></author><author><name sortKey="Shintani, Y" uniqKey="Shintani Y">Y Shintani</name></author><author><name sortKey="Okumura, M" uniqKey="Okumura M">M Okumura</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Vo, Aa" uniqKey="Vo A">AA Vo</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Drobyski, Wr" uniqKey="Drobyski W">WR Drobyski</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Beebe, Kl" uniqKey="Beebe K">KL Beebe</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lee, Sj" uniqKey="Lee S">SJ Lee</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Schoemans, Hm" uniqKey="Schoemans H">HM Schoemans</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cooke, Kr" uniqKey="Cooke K">KR Cooke</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Heinrich, Pc" uniqKey="Heinrich P">PC Heinrich</name></author><author><name sortKey="Behrmann, I" uniqKey="Behrmann I">I Behrmann</name></author><author><name sortKey="Haan, S" uniqKey="Haan S">S Haan</name></author><author><name sortKey="Hermanns, Hm" uniqKey="Hermanns H">HM Hermanns</name></author><author><name sortKey="Muller Newen, G" uniqKey="Muller Newen G">G Müller-Newen</name></author><author><name sortKey="Schaper, F" uniqKey="Schaper F">F Schaper</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Schaeffer, M" uniqKey="Schaeffer M">M Schaeffer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gaensbauer, Jt" uniqKey="Gaensbauer J">JT Gaensbauer</name></author><author><name sortKey="Press, Ca" uniqKey="Press C">CA Press</name></author><author><name sortKey="Hollister, Jr" uniqKey="Hollister J">JR Hollister</name></author><author><name sortKey="Asturias, Ej" uniqKey="Asturias E">EJ Asturias</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list></list><tree><noCountry><name sortKey="Edinger, Matthias" sort="Edinger, Matthias" uniqKey="Edinger M" first="Matthias" last="Edinger">Matthias Edinger</name><name sortKey="Herr, Wolfgang" sort="Herr, Wolfgang" uniqKey="Herr W" first="Wolfgang" last="Herr">Wolfgang Herr</name><name sortKey="Holler, Barbara" sort="Holler, Barbara" uniqKey="Holler B" first="Barbara" last="Holler">Barbara Holler</name><name sortKey="Holler, Ernst" sort="Holler, Ernst" uniqKey="Holler E" first="Ernst" last="Holler">Ernst Holler</name><name sortKey="Kattner, Anna Sophia" sort="Kattner, Anna Sophia" uniqKey="Kattner A" first="Anna-Sophia" last="Kattner">Anna-Sophia Kattner</name><name sortKey="Klobuch, Sebastian" sort="Klobuch, Sebastian" uniqKey="Klobuch S" first="Sebastian" last="Klobuch">Sebastian Klobuch</name><name sortKey="Martinovic, Danilo" sort="Martinovic, Danilo" uniqKey="Martinovic D" first="Danilo" last="Martinovic">Danilo Martinovic</name><name sortKey="Weber, Daniela" sort="Weber, Daniela" uniqKey="Weber D" first="Daniela" last="Weber">Daniela Weber</name><name sortKey="Wolff, Daniel" sort="Wolff, Daniel" uniqKey="Wolff D" first="Daniel" last="Wolff">Daniel 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