新規分子標的薬時代における真菌症マネージメント
近年，分子標的薬，抗体医薬，免疫細胞療法など多種類の新規薬剤の登場により，造血器腫瘍患者の治療成績は向上しつつある。さらに新規治療薬を従来の化学療法や同種移植に組み込んだ新たなプラットフォームの構築が進んでいるが，多くの薬剤を同時に使用するため，薬物間相互作用に留意する必要がある。特に抗真菌薬トリアゾールはCYP阻害作用があるため，CYPの基質である免疫抑制剤，抗がん剤，新規薬剤等と併用した場合にはそれらの薬理作用を増強し，強い毒性が生じる。併用する各薬剤の薬理動態，CYP阻害強度を把握して，投与量の調節や併用開始時期・中止時期を決定することが重要である。...
Saved in:
| Published in | 日本造血・免疫細胞療法学会雑誌 Vol. 14; no. 2; pp. 48 - 56 |
|---|---|
| Main Authors | , |
| Format | Journal Article |
| Language | Japanese |
| Published |
一般社団法人 日本造血・免疫細胞療法学会
2025
|
| Subjects | |
| Online Access | Get full text |
| ISSN | 2436-455X |
| DOI | 10.7889/tct-24-020 |
Cover
| Abstract | 近年，分子標的薬，抗体医薬，免疫細胞療法など多種類の新規薬剤の登場により，造血器腫瘍患者の治療成績は向上しつつある。さらに新規治療薬を従来の化学療法や同種移植に組み込んだ新たなプラットフォームの構築が進んでいるが，多くの薬剤を同時に使用するため，薬物間相互作用に留意する必要がある。特に抗真菌薬トリアゾールはCYP阻害作用があるため，CYPの基質である免疫抑制剤，抗がん剤，新規薬剤等と併用した場合にはそれらの薬理作用を増強し，強い毒性が生じる。併用する各薬剤の薬理動態，CYP阻害強度を把握して，投与量の調節や併用開始時期・中止時期を決定することが重要である。 |
|---|---|
| AbstractList | 近年，分子標的薬，抗体医薬，免疫細胞療法など多種類の新規薬剤の登場により，造血器腫瘍患者の治療成績は向上しつつある。さらに新規治療薬を従来の化学療法や同種移植に組み込んだ新たなプラットフォームの構築が進んでいるが，多くの薬剤を同時に使用するため，薬物間相互作用に留意する必要がある。特に抗真菌薬トリアゾールはCYP阻害作用があるため，CYPの基質である免疫抑制剤，抗がん剤，新規薬剤等と併用した場合にはそれらの薬理作用を増強し，強い毒性が生じる。併用する各薬剤の薬理動態，CYP阻害強度を把握して，投与量の調節や併用開始時期・中止時期を決定することが重要である。 |
| Author | 宮本, 敏浩 森, 康雄 |
| Author_xml | – sequence: 1 fullname: 宮本, 敏浩 organization: 金沢大学医薬保健研究域医学系血液内科学 – sequence: 1 fullname: 森, 康雄 organization: 九州大学病院血液・腫瘍・心血管内科 |
| BookMark | eNo9j8tKw0AARQdRsNZu_I_oZDKPzE4p9QEFNwruhslkoim1SpKNyzSipSrVTaUiiggiqCC4EfRvxqb5DIuKm3MXBy6cGTDZ2mtpAOZsOM9cly8kKrEQtiCCE6CEsEMtTMjWNKjEcehBTBFHNiIlUMv7r8VDb9g5Gr6c54-D0dVh0X_OB-2vj3uTPpm0a9IL0z4ZXd8WvdPR5bHJbkx2ZrJP03432Z3J3kzWmQVTgWzGuvK3ZbC5XNuorlr19ZW16lLdatgulJZGUDkSc-RRpRlmLCA-9bkOONIUEmUznzKlKLMxDAgNGOeKIuqRwCGQSeSUweLvbyNO5LYW-1G4K6MDIaMkVE0txtXCxgL9AItx_b9SOzISDel8A3FQba0 |
| ContentType | Journal Article |
| Copyright | 2025 一般社団法人日本造血・免疫細胞療法学会 |
| Copyright_xml | – notice: 2025 一般社団法人日本造血・免疫細胞療法学会 |
| DOI | 10.7889/tct-24-020 |
| DatabaseTitleList | |
| DeliveryMethod | fulltext_linktorsrc |
| EISSN | 2436-455X |
| EndPage | 56 |
| ExternalDocumentID | article_tct_14_2_14_24_020_article_char_ja |
| GroupedDBID | JSF RJT |
| ID | FETCH-LOGICAL-j180a-e20c3a492b6ce7477f5d6d9ef92e605c17d67cc67140f56f799c626b5f3507a23 |
| IngestDate | Wed Sep 03 06:30:36 EDT 2025 |
| IsDoiOpenAccess | true |
| IsOpenAccess | true |
| IsPeerReviewed | false |
| IsScholarly | false |
| Issue | 2 |
| Language | Japanese |
| LinkModel | OpenURL |
| MergedId | FETCHMERGED-LOGICAL-j180a-e20c3a492b6ce7477f5d6d9ef92e605c17d67cc67140f56f799c626b5f3507a23 |
| OpenAccessLink | https://www.jstage.jst.go.jp/article/tct/14/2/14_24-020/_article/-char/ja |
| PageCount | 9 |
| ParticipantIDs | jstage_primary_article_tct_14_2_14_24_020_article_char_ja |
| PublicationCentury | 2000 |
| PublicationDate | 2025 |
| PublicationDateYYYYMMDD | 2025-01-01 |
| PublicationDate_xml | – year: 2025 text: 2025 |
| PublicationDecade | 2020 |
| PublicationTitle | 日本造血・免疫細胞療法学会雑誌 |
| PublicationTitleAlternate | にほんぞうけつ・めんえきさいぼうりょうほうがっかいざっし |
| PublicationYear | 2025 |
| Publisher | 一般社団法人 日本造血・免疫細胞療法学会 |
| Publisher_xml | – name: 一般社団法人 日本造血・免疫細胞療法学会 |
| References | 24. Little JS, Weiss ZF, Hammond SP. Invasive fungal infections and targeted therapies in hematological malignancies. J Fungi (Basel). 2021; 7: 1058. 20. Kang D, Ludwig E, Jaworowicz D, et al. Concentration-QTc analysis of quizartinib in patients with relapsed/refractory acute myeloid leukemia. Cancer Chemother Pharmacol. 2021; 87: 513-523. 11. Roboz GJ, Canaani J. How I use maintenance therapy in acute myeloid leukemia. Blood. 2024 Oct 7: blood.2024024010. Online ahead of print. 22. DiNardo CD, Jonas BA, Pullarkat V, et al. Azacitidine and venetoclax in previous untreated acute myeloid leukemia. N Engl J Med. 2020; 383: 617-629. 26. Donnelly JP, Chen SC, Kauffman CA, et al. Revision and update of the consensus definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer and the Mycoses Study Group education and research consortium. Clin Infect Dis. 2020; 71: 1367-1376. 19. Erba HP, Montesinos P, Kim HJ, et al. Quizartinib plus chemotherapy in newly diagnosed patients with FLT3-internal-tendem-duplication-positive acute myeloid leukaemia (QuANTUM-First): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2023; 401: 1571-1583. 23. Wei AH, Loo S, Daver NG. How I treat patients with AML using azacitidine and venetoclax. Blood. 2024: blood.2024024009. Online ahead of print. 27. Gerner B, Aghai-Trommeschlaeger F, Kraus S, et al. A physiologically-based pharmacokinetic model of ruxolitinib and posaconazole to predict CYP3A4-mediated drug-drug interaction frequently observed in graft versus host disease patients. Pharmaceutics. 2022; 14: 2556. 4. Sugimoto M, Yonezawa A, Kanda J, et al. Population pharmacokinetic modeling of posaconazole in Japanese patients receiving fungal prophylaxis. Ther Drug Monit. 2024; 46: 611-618. 3. Yamada T, Belabbas T, Suetsugu K, et al. Factors influencing serum posaconazole concentrations in patients with hematologic malignancies receiving delayed-release tablets. Ther Drug Monit. 2024; 46: 603-610. 15. Garrison DA, Jin Y, Talebi Z, et al. Itraconazole-induced increases in gilteritinib exposure are mediated by CYP3A and OATP1B. Molecules. 2022; 27: 6815. 16. DiNardo CD and Wei AH. How I treat acute myeloid leukemia in the era of new drugs. Blood. 2020; 135: 85-96. 5. Marshall WL, McCrea JB, Macha S, et al. Pharmacokinetics and tolerability of letermovir coadministered with azole antifungals (posaconazole or voriconazole) in healthy subjects. J Clin Pharmacol.2018; 58: 897-904. 18. Terao T, Matsuoka K-I, Ueda H, et al. Early initiation of low-dose gilteritinib maintenance improves posttransplant outcomes in patients with R/R FLT3mut AML. Blood Adv.2023; 7: 681-686. 25. Sayabovorn N, Chongtrakool P, Chayakulkeeree M. Cryptococcal fungemia and mycobacterium haemophilum cellulitis in a patient receiving ruxolitinib: a case report and literature review. BMC Infect Dis. 2021; 21: 27. 1. 造血細胞移植ガイドライン真菌感染症の予防と治療 (第3版) 2024年9月, 一般社団法人日本造血・免疫細胞療法学会. (https://www.jstct.or.jp/uploads/files/guideline/01_04_shinkin03n.pdf) 7. Hikasa S, Shimabukuro S, Osugi Y, et al. Decrease in voriconazole concentration-to-dose ratio after letermovir initiation: a retrospective, observational study. Bone Marrow Transplant. 2021; 56: 949-951. 10. DeFilipp Z, Ciurea SO, Cutler C, et al. Hematopoietic cell transplantation in the management of myelodysplastic syndrome: An evidence-based review from the American Society for Transplantation and Cellular Therapy committee on practice guidelines. Transplant Cell Ther. 2023; 29: 71-81. 13. Perl A, Martinelli G, Cortes JE, et al. Gilteritinib or chemotherapy for relapsed or refractory FLT3-mutated AML. N Engl J Med. 2019; 381: 1728-1740. 2. ECIL-6 Triazole Antifungal Therapeutic Drug Monitoring. (https://www.ecil-leukaemia.com/images/resources/2015/5_ECIL6-Triazole-TDM-07-12-2015-Lewis-R-et-al.pdf) 8. Nakashima T, Inamoto Y, Fukushi Y, et al. Drug interaction between letermovir and voriconazole after allogeneic hematopoietic cell transplantation. Int J Hematol. 2021; 113: 872-876. 12. Saini N, Marin D, Ledesma C, et al. Impact of TKIs post-allogeneic hematopoietic cell transplantation in Philadelphia chromosome-positive ALL. Blood. 2020; 136: 1786-1789. 6. Suetsugu K, Muraki S, Fukumoto J, et al. Effects of letermovir and/or methylprednisolone coadministration on voriconazole pharmacokinetics in hematopoietic stem cell transplantation: A population pharmacokinetic study. Drugs R D. 2021; 21: 419-429. 17. Levis MJ, Hamadani M, Logan B, et al. Gilteritinib as post-transplant maintenance for AML with internal tandem duplication of FLT3. J Clin Oncol. 2024; 42: 1766-1775. 9. Terrier J, Zanella MC, Masouridi-Levrat S, et al. Clinical and pharmacological considerations for concomitant administration of posaconazole and isavuconazole with letermovir. Antimicrob Agents Chemother. 2021; 65: e00274-21. 21. Mellinghoff SC, Bassetti M, Dörfel D, et al. Isavuconazole shortens the QTc interval. Mycoses. 2018; 61: 256-260. 14. Aleissa MM, Alshehri BS, Gonzalez-Bocco IH, et al. Triazole antifungal use for prophylaxis and treatment of invasive fungal diseases for patients receiving gilteritinib. Leuk Res. 2021; 108. |
| References_xml | – reference: 27. Gerner B, Aghai-Trommeschlaeger F, Kraus S, et al. A physiologically-based pharmacokinetic model of ruxolitinib and posaconazole to predict CYP3A4-mediated drug-drug interaction frequently observed in graft versus host disease patients. Pharmaceutics. 2022; 14: 2556. – reference: 26. Donnelly JP, Chen SC, Kauffman CA, et al. Revision and update of the consensus definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer and the Mycoses Study Group education and research consortium. Clin Infect Dis. 2020; 71: 1367-1376. – reference: 19. Erba HP, Montesinos P, Kim HJ, et al. Quizartinib plus chemotherapy in newly diagnosed patients with FLT3-internal-tendem-duplication-positive acute myeloid leukaemia (QuANTUM-First): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2023; 401: 1571-1583. – reference: 8. Nakashima T, Inamoto Y, Fukushi Y, et al. Drug interaction between letermovir and voriconazole after allogeneic hematopoietic cell transplantation. Int J Hematol. 2021; 113: 872-876. – reference: 4. Sugimoto M, Yonezawa A, Kanda J, et al. Population pharmacokinetic modeling of posaconazole in Japanese patients receiving fungal prophylaxis. Ther Drug Monit. 2024; 46: 611-618. – reference: 18. Terao T, Matsuoka K-I, Ueda H, et al. Early initiation of low-dose gilteritinib maintenance improves posttransplant outcomes in patients with R/R FLT3mut AML. Blood Adv.2023; 7: 681-686. – reference: 21. Mellinghoff SC, Bassetti M, Dörfel D, et al. Isavuconazole shortens the QTc interval. Mycoses. 2018; 61: 256-260. – reference: 22. DiNardo CD, Jonas BA, Pullarkat V, et al. Azacitidine and venetoclax in previous untreated acute myeloid leukemia. N Engl J Med. 2020; 383: 617-629. – reference: 7. Hikasa S, Shimabukuro S, Osugi Y, et al. Decrease in voriconazole concentration-to-dose ratio after letermovir initiation: a retrospective, observational study. Bone Marrow Transplant. 2021; 56: 949-951. – reference: 17. Levis MJ, Hamadani M, Logan B, et al. Gilteritinib as post-transplant maintenance for AML with internal tandem duplication of FLT3. J Clin Oncol. 2024; 42: 1766-1775. – reference: 10. DeFilipp Z, Ciurea SO, Cutler C, et al. Hematopoietic cell transplantation in the management of myelodysplastic syndrome: An evidence-based review from the American Society for Transplantation and Cellular Therapy committee on practice guidelines. Transplant Cell Ther. 2023; 29: 71-81. – reference: 9. Terrier J, Zanella MC, Masouridi-Levrat S, et al. Clinical and pharmacological considerations for concomitant administration of posaconazole and isavuconazole with letermovir. Antimicrob Agents Chemother. 2021; 65: e00274-21. – reference: 25. Sayabovorn N, Chongtrakool P, Chayakulkeeree M. Cryptococcal fungemia and mycobacterium haemophilum cellulitis in a patient receiving ruxolitinib: a case report and literature review. BMC Infect Dis. 2021; 21: 27. – reference: 20. Kang D, Ludwig E, Jaworowicz D, et al. Concentration-QTc analysis of quizartinib in patients with relapsed/refractory acute myeloid leukemia. Cancer Chemother Pharmacol. 2021; 87: 513-523. – reference: 11. Roboz GJ, Canaani J. How I use maintenance therapy in acute myeloid leukemia. Blood. 2024 Oct 7: blood.2024024010. Online ahead of print. – reference: 24. Little JS, Weiss ZF, Hammond SP. Invasive fungal infections and targeted therapies in hematological malignancies. J Fungi (Basel). 2021; 7: 1058. – reference: 13. Perl A, Martinelli G, Cortes JE, et al. Gilteritinib or chemotherapy for relapsed or refractory FLT3-mutated AML. N Engl J Med. 2019; 381: 1728-1740. – reference: 6. Suetsugu K, Muraki S, Fukumoto J, et al. Effects of letermovir and/or methylprednisolone coadministration on voriconazole pharmacokinetics in hematopoietic stem cell transplantation: A population pharmacokinetic study. Drugs R D. 2021; 21: 419-429. – reference: 3. Yamada T, Belabbas T, Suetsugu K, et al. Factors influencing serum posaconazole concentrations in patients with hematologic malignancies receiving delayed-release tablets. Ther Drug Monit. 2024; 46: 603-610. – reference: 23. Wei AH, Loo S, Daver NG. How I treat patients with AML using azacitidine and venetoclax. Blood. 2024: blood.2024024009. Online ahead of print. – reference: 12. Saini N, Marin D, Ledesma C, et al. Impact of TKIs post-allogeneic hematopoietic cell transplantation in Philadelphia chromosome-positive ALL. Blood. 2020; 136: 1786-1789. – reference: 5. Marshall WL, McCrea JB, Macha S, et al. Pharmacokinetics and tolerability of letermovir coadministered with azole antifungals (posaconazole or voriconazole) in healthy subjects. J Clin Pharmacol.2018; 58: 897-904. – reference: 15. Garrison DA, Jin Y, Talebi Z, et al. Itraconazole-induced increases in gilteritinib exposure are mediated by CYP3A and OATP1B. Molecules. 2022; 27: 6815. – reference: 14. Aleissa MM, Alshehri BS, Gonzalez-Bocco IH, et al. Triazole antifungal use for prophylaxis and treatment of invasive fungal diseases for patients receiving gilteritinib. Leuk Res. 2021; 108. – reference: 16. DiNardo CD and Wei AH. How I treat acute myeloid leukemia in the era of new drugs. Blood. 2020; 135: 85-96. – reference: 1. 造血細胞移植ガイドライン真菌感染症の予防と治療 (第3版) 2024年9月, 一般社団法人日本造血・免疫細胞療法学会. (https://www.jstct.or.jp/uploads/files/guideline/01_04_shinkin03n.pdf) – reference: 2. ECIL-6 Triazole Antifungal Therapeutic Drug Monitoring. (https://www.ecil-leukaemia.com/images/resources/2015/5_ECIL6-Triazole-TDM-07-12-2015-Lewis-R-et-al.pdf) |
| SSID | ssib046292125 ssib050736134 ssj0003322003 |
| Score | 2.002544 |
| Snippet | 近年，分子標的薬，抗体医薬，免疫細胞療法など多種類の新規薬剤の登場により，造血器腫瘍患者の治療成績は向上しつつある。さらに新規治療薬を従来の化学療法や同種移植に... |
| SourceID | jstage |
| SourceType | Publisher |
| StartPage | 48 |
| SubjectTerms | CYP3A4 inhibitor drug-drug interactions hematological malignancy novel targeted agent triazole |
| Title | 新規分子標的薬時代における真菌症マネージメント |
| URI | https://www.jstage.jst.go.jp/article/tct/14/2/14_24-020/_article/-char/ja |
| Volume | 14 |
| hasFullText | 1 |
| inHoldings | 1 |
| isFullTextHit | |
| isPrint | |
| ispartofPNX | 日本造血・免疫細胞療法学会雑誌, 2025, Vol.14(2), pp.48-56 |
| journalDatabaseRights | – providerCode: PRVHPJ databaseName: ROAD: Directory of Open Access Scholarly Resources databaseCode: M~E dateStart: 20210101 customDbUrl: isFulltext: true eissn: 2436-455X dateEnd: 99991231 titleUrlDefault: https://road.issn.org omitProxy: true ssIdentifier: ssib050736134 providerName: ISSN International Centre |
| link | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwxR3LahRBcIjx4kUUFd_kYJ9kdKbffeyZTAiCnhLIbZjnYQ9RZHPxIGxWNPggeolERBFBBBUEL4L-zZjHD3i3uqdnsoqHqAdhaWp6q6vrsb1V1XTXeN6Fog5EJknmF_D351MRVL6s8xIes7oKyyzD0lxwvnqNzy_SK0tsaerA94lTSyvD_FJx67f3Sv7GqtAHdjW3ZP_Asj1R6AAY7AstWBjafdkYJRwpjqIAJRJpjuQcShiSEkluAD2LVGBwtERKoUQgpZGkBhlG6dgOV0hilFAURUgTlBAILZGOHCC1A1RoAYxkZOnESM0ZOjCjjG2PQFJYHIJU4gA564AodsMj6Xp02H1FOmQ5GShb3gTSzAKx5VaZYxm6FTY0sKMQWamZnU5Y0SyTEXWacSyJTlhuJlXMqQj0ZsSPjXJgChVZYWEK0FW_hWxxE_Pp2YHfpn1gVu1AEzDUHj436tRJi8ZQpFEkHP32bXXdXkt7I9uuC8uItJJJY0ZtVauhMzE0VGuinn1qqeqL_0VXrWe3LgRTwn3K2NJP_o5OrGs84bzakqcuDGrLvf_qYIWUpj7tsBj6mPoBDvbCiP5wp1sOKSBBYpli29AUkNPuK3OjMB1AWnMQm200c-L2dtK5AcqxgoCqdzOQsRAIOmm_dUrACUHbFhs2HF3e4wcCyQGkVd2RTBslLhzxDrv0bka3HBz1pgbZMS_Z3vi4-2Z9a-3u1ofH2283d57d2d14v725-u3L62b0rhndb0ZPmtUHO89f7q4_3Hl6rxm_aMaPmvHXZvVzM37VjD8147Xj3uJcshDP--71Jf4glEHmVzgoSEYVznlRQdYualbyUlW1whUPWBGKkoui4KZkZs14LZQqOOY5qwmInGFywptevr5cnfRmBK3DOg_rQpSMcpVnMsM5JTgkuCyDIjzlqVbq9EZboybdvxFO_8PYM94hs0zaLcmz3vTw5kp1DoL0YX7emvQHLsO1bA |
| linkProvider | ISSN International Centre |
| openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=%E6%96%B0%E8%A6%8F%E5%88%86%E5%AD%90%E6%A8%99%E7%9A%84%E8%96%AC%E6%99%82%E4%BB%A3%E3%81%AB%E3%81%8A%E3%81%91%E3%82%8B%E7%9C%9F%E8%8F%8C%E7%97%87%E3%83%9E%E3%83%8D%E3%83%BC%E3%82%B8%E3%83%A1%E3%83%B3%E3%83%88&rft.jtitle=%E6%97%A5%E6%9C%AC%E9%80%A0%E8%A1%80%E3%83%BB%E5%85%8D%E7%96%AB%E7%B4%B0%E8%83%9E%E7%99%82%E6%B3%95%E5%AD%A6%E4%BC%9A%E9%9B%91%E8%AA%8C&rft.au=%E5%AE%AE%E6%9C%AC%2C+%E6%95%8F%E6%B5%A9&rft.au=%E6%A3%AE%2C+%E5%BA%B7%E9%9B%84&rft.date=2025&rft.pub=%E4%B8%80%E8%88%AC%E7%A4%BE%E5%9B%A3%E6%B3%95%E4%BA%BA+%E6%97%A5%E6%9C%AC%E9%80%A0%E8%A1%80%E3%83%BB%E5%85%8D%E7%96%AB%E7%B4%B0%E8%83%9E%E7%99%82%E6%B3%95%E5%AD%A6%E4%BC%9A&rft.eissn=2436-455X&rft.volume=14&rft.issue=2&rft.spage=48&rft.epage=56&rft_id=info:doi/10.7889%2Ftct-24-020&rft.externalDocID=article_tct_14_2_14_24_020_article_char_ja |