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Six-week oral prednisolone therapy for immune-related pneumonitis: a single-arm phase II study

BACKGROUND: There has been no prospective trial for treatment of immune-related pneumonitis (irP) occurred after immune checkpoint inhibitors (ICIs). METHODS: In this single-arm phase II study, patients with cancer with grade ≥2 irP received oral prednisolone (1 mg/kg/day), tapered over 6 weeks. The...

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Autores principales: Karayama, Masato, Inui, Naoki, Inoue, Yusuke, Yasui, Hideki, Hozumi, Hironao, Suzuki, Yuzo, Furuhashi, Kazuki, Fujisawa, Tomoyuki, Enomoto, Noriyuki, Asada, Kazuhiro, Uto, Tomohiro, Fujii, Masato, Matsui, Takashi, Matsuura, Shun, Hashimoto, Dai, Toyoshima, Mikio, Ikeda, Masaki, Matsuda, Hiroyuki, Inami, Nao, Kaida, Yusuke, Funayama, Satoshi, Ichikawa, Shintaro, Goshima, Satoshi, Suda, Takafumi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10387737/
https://www.ncbi.nlm.nih.gov/pubmed/37500182
http://dx.doi.org/10.1136/jitc-2023-007056
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author Karayama, Masato
Inui, Naoki
Inoue, Yusuke
Yasui, Hideki
Hozumi, Hironao
Suzuki, Yuzo
Furuhashi, Kazuki
Fujisawa, Tomoyuki
Enomoto, Noriyuki
Asada, Kazuhiro
Uto, Tomohiro
Fujii, Masato
Matsui, Takashi
Matsuura, Shun
Hashimoto, Dai
Toyoshima, Mikio
Ikeda, Masaki
Matsuda, Hiroyuki
Inami, Nao
Kaida, Yusuke
Funayama, Satoshi
Ichikawa, Shintaro
Goshima, Satoshi
Suda, Takafumi
author_facet Karayama, Masato
Inui, Naoki
Inoue, Yusuke
Yasui, Hideki
Hozumi, Hironao
Suzuki, Yuzo
Furuhashi, Kazuki
Fujisawa, Tomoyuki
Enomoto, Noriyuki
Asada, Kazuhiro
Uto, Tomohiro
Fujii, Masato
Matsui, Takashi
Matsuura, Shun
Hashimoto, Dai
Toyoshima, Mikio
Ikeda, Masaki
Matsuda, Hiroyuki
Inami, Nao
Kaida, Yusuke
Funayama, Satoshi
Ichikawa, Shintaro
Goshima, Satoshi
Suda, Takafumi
author_sort Karayama, Masato
collection PubMed
description BACKGROUND: There has been no prospective trial for treatment of immune-related pneumonitis (irP) occurred after immune checkpoint inhibitors (ICIs). METHODS: In this single-arm phase II study, patients with cancer with grade ≥2 irP received oral prednisolone (1 mg/kg/day), tapered over 6 weeks. The primary endpoint was a pneumonitis control rate at 6 weeks from the start of the study treatment, defined as complete disappearance or partial improvement of irP in high-resolution CT of the chest. RESULTS: Among 57 patients enrolled, 56 were included in the final analysis. The most frequent cause of irP was single ICI therapy (51.8%), followed by combination with chemotherapy plus ICI (39.3%). Thirty-five (62.5%) patients had grade 2 irP and 21 (37.5%) had grade ≥3. Fifty-one (91.1%) patients completed the study treatment while 5 discontinued the study treatment because of relapse of irP (n=1), death from cancer (n=1), occurrence of immune-related hepatitis (n=1), extension of the treatment duration more than 6 weeks (n=1), and attending physician’s decision (n=1). Six weeks after the start of the study treatment, 16 (28.5%) patients demonstrated complete recovery from irP, 35 (62.5%) had a partial improvement in irP, 1 (1.8%) had a relapse of irP, and 4 (7.1%) were not evaluable. The pneumonitis control rate at 6 weeks was 91.1% (95% CI, 80.7% to 96.1%). Twelve weeks after the start of the study treatment, 5 (8.9%), 27 (48.2%), and 15 (26.8%) patients demonstrated complete recovery, partial improvement, and relapse, respectively, and 9 (16.1%) were not evaluable. The pneumonitis control rate at 12 weeks was 57.1% (95% CI, 44.1% to 69.2%). During the observation period, 18 (32.1%) patients experienced a relapse of irP, and of those, 17 received re-treatment with corticosteroids. Grade ≥3 adverse events occurred in 10 (17.9%) patients, in which hyperglycemia was most frequent (n=6). There was no treatment-related death. CONCLUSIONS: In this first prospective study for irP, prednisolone at 1 mg/kg/day, tapered over 6 weeks, demonstrated a promising clinical benefit and manageable toxicity, suggesting a potential treatment option for irP. TRIAL REGISTRATION NUMBER: jRCT: 1041190029.
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spelling pubmed-103877372023-08-01 Six-week oral prednisolone therapy for immune-related pneumonitis: a single-arm phase II study Karayama, Masato Inui, Naoki Inoue, Yusuke Yasui, Hideki Hozumi, Hironao Suzuki, Yuzo Furuhashi, Kazuki Fujisawa, Tomoyuki Enomoto, Noriyuki Asada, Kazuhiro Uto, Tomohiro Fujii, Masato Matsui, Takashi Matsuura, Shun Hashimoto, Dai Toyoshima, Mikio Ikeda, Masaki Matsuda, Hiroyuki Inami, Nao Kaida, Yusuke Funayama, Satoshi Ichikawa, Shintaro Goshima, Satoshi Suda, Takafumi J Immunother Cancer Clinical/Translational Cancer Immunotherapy BACKGROUND: There has been no prospective trial for treatment of immune-related pneumonitis (irP) occurred after immune checkpoint inhibitors (ICIs). METHODS: In this single-arm phase II study, patients with cancer with grade ≥2 irP received oral prednisolone (1 mg/kg/day), tapered over 6 weeks. The primary endpoint was a pneumonitis control rate at 6 weeks from the start of the study treatment, defined as complete disappearance or partial improvement of irP in high-resolution CT of the chest. RESULTS: Among 57 patients enrolled, 56 were included in the final analysis. The most frequent cause of irP was single ICI therapy (51.8%), followed by combination with chemotherapy plus ICI (39.3%). Thirty-five (62.5%) patients had grade 2 irP and 21 (37.5%) had grade ≥3. Fifty-one (91.1%) patients completed the study treatment while 5 discontinued the study treatment because of relapse of irP (n=1), death from cancer (n=1), occurrence of immune-related hepatitis (n=1), extension of the treatment duration more than 6 weeks (n=1), and attending physician’s decision (n=1). Six weeks after the start of the study treatment, 16 (28.5%) patients demonstrated complete recovery from irP, 35 (62.5%) had a partial improvement in irP, 1 (1.8%) had a relapse of irP, and 4 (7.1%) were not evaluable. The pneumonitis control rate at 6 weeks was 91.1% (95% CI, 80.7% to 96.1%). Twelve weeks after the start of the study treatment, 5 (8.9%), 27 (48.2%), and 15 (26.8%) patients demonstrated complete recovery, partial improvement, and relapse, respectively, and 9 (16.1%) were not evaluable. The pneumonitis control rate at 12 weeks was 57.1% (95% CI, 44.1% to 69.2%). During the observation period, 18 (32.1%) patients experienced a relapse of irP, and of those, 17 received re-treatment with corticosteroids. Grade ≥3 adverse events occurred in 10 (17.9%) patients, in which hyperglycemia was most frequent (n=6). There was no treatment-related death. CONCLUSIONS: In this first prospective study for irP, prednisolone at 1 mg/kg/day, tapered over 6 weeks, demonstrated a promising clinical benefit and manageable toxicity, suggesting a potential treatment option for irP. TRIAL REGISTRATION NUMBER: jRCT: 1041190029. BMJ Publishing Group 2023-07-27 /pmc/articles/PMC10387737/ /pubmed/37500182 http://dx.doi.org/10.1136/jitc-2023-007056 Text en © Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) .
spellingShingle Clinical/Translational Cancer Immunotherapy
Karayama, Masato
Inui, Naoki
Inoue, Yusuke
Yasui, Hideki
Hozumi, Hironao
Suzuki, Yuzo
Furuhashi, Kazuki
Fujisawa, Tomoyuki
Enomoto, Noriyuki
Asada, Kazuhiro
Uto, Tomohiro
Fujii, Masato
Matsui, Takashi
Matsuura, Shun
Hashimoto, Dai
Toyoshima, Mikio
Ikeda, Masaki
Matsuda, Hiroyuki
Inami, Nao
Kaida, Yusuke
Funayama, Satoshi
Ichikawa, Shintaro
Goshima, Satoshi
Suda, Takafumi
Six-week oral prednisolone therapy for immune-related pneumonitis: a single-arm phase II study
title Six-week oral prednisolone therapy for immune-related pneumonitis: a single-arm phase II study
title_full Six-week oral prednisolone therapy for immune-related pneumonitis: a single-arm phase II study
title_fullStr Six-week oral prednisolone therapy for immune-related pneumonitis: a single-arm phase II study
title_full_unstemmed Six-week oral prednisolone therapy for immune-related pneumonitis: a single-arm phase II study
title_short Six-week oral prednisolone therapy for immune-related pneumonitis: a single-arm phase II study
title_sort six-week oral prednisolone therapy for immune-related pneumonitis: a single-arm phase ii study
topic Clinical/Translational Cancer Immunotherapy
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10387737/
https://www.ncbi.nlm.nih.gov/pubmed/37500182
http://dx.doi.org/10.1136/jitc-2023-007056
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