移植後維持療法の現在と将来展望
造血細胞移植後の再発は，現代の移植医療が解決すべき最重要課題のひとつである。この10年間，ゲノミクスの進歩を背景として新しい抗腫瘍薬開発が着実に進捗している。これまでの移植では，高強度前処置と同種免疫反応によって残存腫瘍の根絶が目指されたが，最近では新規薬剤を移植の前後に組み込み，①移植前の残存腫瘍量を最小化するとともに（移植ブリッジング），②移植後治療で再発を抑制する（移植後維持療法），という新たな戦略が模索されている。特に標的を有する病型における移植後維持療法は，その安全性と有効性が明らかにされ，移植医療のシェーマそのものを書き換えつつある。今後のゲノムスクリーニングと高感度MRD測定の臨...
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| Published in | 日本造血・免疫細胞療法学会雑誌 Vol. 13; no. 1; pp. 1 - 13 |
|---|---|
| Main Author | |
| Format | Journal Article |
| Language | Japanese |
| Published |
一般社団法人 日本造血・免疫細胞療法学会
2024
|
| Subjects | |
| Online Access | Get full text |
| ISSN | 2436-455X |
| DOI | 10.7889/tct-23-025 |
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| Abstract | 造血細胞移植後の再発は，現代の移植医療が解決すべき最重要課題のひとつである。この10年間，ゲノミクスの進歩を背景として新しい抗腫瘍薬開発が着実に進捗している。これまでの移植では，高強度前処置と同種免疫反応によって残存腫瘍の根絶が目指されたが，最近では新規薬剤を移植の前後に組み込み，①移植前の残存腫瘍量を最小化するとともに（移植ブリッジング），②移植後治療で再発を抑制する（移植後維持療法），という新たな戦略が模索されている。特に標的を有する病型における移植後維持療法は，その安全性と有効性が明らかにされ，移植医療のシェーマそのものを書き換えつつある。今後のゲノムスクリーニングと高感度MRD測定の臨床実装は，必要十分な移植後治療を適切に実施する基盤となろう。客観的情報に基づくアプローチが確立できれば，移植後治療においても個別化医療の流れが大きく加速し，より安全で効果的な移植後マネジメントが実現される。 |
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| AbstractList | 造血細胞移植後の再発は，現代の移植医療が解決すべき最重要課題のひとつである。この10年間，ゲノミクスの進歩を背景として新しい抗腫瘍薬開発が着実に進捗している。これまでの移植では，高強度前処置と同種免疫反応によって残存腫瘍の根絶が目指されたが，最近では新規薬剤を移植の前後に組み込み，①移植前の残存腫瘍量を最小化するとともに（移植ブリッジング），②移植後治療で再発を抑制する（移植後維持療法），という新たな戦略が模索されている。特に標的を有する病型における移植後維持療法は，その安全性と有効性が明らかにされ，移植医療のシェーマそのものを書き換えつつある。今後のゲノムスクリーニングと高感度MRD測定の臨床実装は，必要十分な移植後治療を適切に実施する基盤となろう。客観的情報に基づくアプローチが確立できれば，移植後治療においても個別化医療の流れが大きく加速し，より安全で効果的な移植後マネジメントが実現される。 |
| Author | 松岡, 賢市 |
| Author_xml | – sequence: 1 fullname: 松岡, 賢市 organization: 岡山大学学術研究院医歯薬学域 血液・腫瘍・呼吸器内科学 |
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| Copyright | 2024 一般社団法人日本造血・免疫細胞療法学会 |
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| References_xml | – reference: 15. Burchert A, Bug G, Fritz LV, et al. Sorafenib maintenance after allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia with FLT3-internal tandem duplication mutation (SORMAIN). J Clin Oncol. 2020; 38: 2993-3002. – reference: 11. Levis MJ, Perl AE, Altman JK, et al. A next-generation sequencing-based assay for minimal residual disease assessment in AML patients with FLT3-ITD mutations. Blood Adv. 2018; 2: 825-831. – reference: 23. D Gary Gilliland 1, James D Griffin. The roles of FLT3 in hematopoiesis and leukemia. Blood. 2002; 100: 1532-1542. – reference: 32. Goodyear OC, Dennis M, Jilani NY, et al. Azacitidine augments expansion of regulatory T cells after allogeneic stem cell transplantation in patients with acute myeloid leukemia (AML). Blood. 2012; 119: 3361-3369. – reference: 16. Xuan L, Wang Y, Huang F, et al. Sorafenib maintenance in patients with FLT3-ITD acute myeloid leukaemia undergoing allogeneic haematopoietic stem-cell transplantation: an open-label, multicentre, randomized phase 3 trial. Lancet Oncol. 2020; 21: 1201-1212. – reference: 8. Salut B, Myriam L, Jordi E, et al. Impact of FLT3 internal tandem duplication on the outcome of related and unrelated hematopoietic transplantation for adult acute myeloid leukemia in first remission: a retrospective analysis. J Clin Oncol. 2012; 30: 735-741. – reference: 26. Carpenter PA, Snyder DS, Flowers ME, et al. Prophylactic administration of imatinib after hematopoietic cell transplantation for high-risk Philadelphia chromosome-positive leukemia. Blood. 2007; 109: 2791-2793. – reference: 29. 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: 24. Milne P, Wilhelm-Benartzi C, Grunwald MR, et al. Serum Flt3 ligand is a biomarker of progenitor cell mass and prognosis in acute myeloid leukemia. Blood Adv. 2019; 3: 3052-3061. – reference: 3. Robert Zeiser, Luca Vago. Mechanisms of immune escape after allogeneic hematopoietic cell transplantation. Blood. 2019; 133: 1290-1297. – reference: 28. Ribera JM, Oriol A, Gonzalez M, et al. Grupo Espanol de Trasplante Hemopoyetico Groups. Concurrent intensive chemotherapy and imatinib before and after stem cell transplan-tation in newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia. Final results of the CSTIBES02 trial. Haematologica. 2010; 95: 87-95. – reference: 44. Wei AH, Ribera JM, Larson RA, et al. Biomarkers associated with blinatumomab outcomes in acute lymphoblastic leukemia. Leukemia. 2021; 35: 2220-2231. – reference: 6. Penter L, Zhang Y, Savell A, et al. Molecular and cellular features of CTLA-4 blockade for relapsed myeloid malignancies after transplantation. Blood. 2021; 137: 3212-3217. – reference: 18. Perl AE, Larson RA, Podoltsev NA, et al. Follow-up of patients with R/R FLT3-mutation-positive AML treated with gilteritinib in the phase 3 ADMIRAL trial. Blood. 2022; 139: 3366-3375. – reference: 13. Grob T, Sanders MA, Vonk CM, et al. Prognostic Value of FLT3-Internal Tandem Duplication Residual Disease in Acute Myeloid Leukemia. J Clin Oncol. 2023; 41: 756-765. – reference: 1. Senapati J, Kadia TM, Ravandi F. Maintenance therapy in acute myeloid leukemia: advances and controversies. Haematologica. 2023; 108: 2289-2304. – reference: 12. Loo S, Dillon R, Ivey A, et al. Pretransplant FLT3-ITD MRD assessed by high-sensitivity PCR-NGS determines posttransplant clinical outcome. Blood. 2022; 140: 2407-2411. – reference: 39. Lindsley RC, Saber W, Mar BG, et al. Prognostic Mutations in Myelodysplastic Syndrome after Stem-Cell Transplantation. N Engl J Med 2017; 376: 536-547. – reference: 20. Cortes JE, Khaled S, Martinelli G, et al. Quizartinib versus salvage chemotherapy in relapsed or refractory FLT3-ITD acute myeloid leukaemia (QuANTUM-R): a multicentre, randomised, controlled, open-label, phase 3 trial. Lancet Oncol. 2019; 20: 984-997. – reference: 27. Olavarria E, Siddique S, Griffiths MJ, et al. Posttransplantation imatinib as a strategy to postpone the requirement for immuno-therapy in patients undergoing reduced-intensity allografts for chronic myeloid leukemia. Blood. 2007; 110: 4614-4617. – reference: 47. Cerchione C, Romano A, Daver N, et al. IDH1/IDH2 inhibition in acute myeloid leukemia. Front Oncol. 2021; 11: 639387. – reference: 48. Fathi AT, Li S, Soiffer RJ, et al. A phase I study of the IDH2 inhibitor enasidenib as maintenance therapy for IDH2-mutant myeloid neoplasms following hematopoietic cell transplantation. Blood. 2020; 136: 4-5. – reference: 46. Chauvet P, Paviglianiti A, Labopin M, et al. Combining blinatumomab and donor lymphocyte infusion in B-ALL patients relapsing after allogeneic hematopoietic cell transplantation: a study of the SFGM-TC. Bone Marrow Transplant. 2023; 58: 72-79. – reference: 19. Perl AE, Larson RA, Podoltsev NA, et al. Outcomes in Patients with FLT3-Mutated Relapsed/Refractory Acute Myelogenous Leukemia Who Underwent Transplantation in the Phase 3 ADMIRAL Trial of Gilteritinib versus Salvage Chemotherapy. Transplant Cell Ther. 2023; 29: 265-265. – reference: 34. Oran B, de Lima M, Garcia-Manero G, et al. A phase 3 randomized study of 5-azacitidine maintenance vs observation after transplant in high-risk AML and MDS patients. Blood Adv. 2020; 4: 5580-5588. – reference: 17. Maziarz RT, Levis M, Patnaik MM, et al. Midostaurin after allogeneic stem cell transplant in patients with FLT3-internal tandem duplication-positive acute myeloid leukemia. Bone Marrow Transplantation. 2021; 56: 1180-1189. – reference: 42. Wei Y, Xiong X, Li X, et al. Low-dose decitabine plus venetoclax is safe and effective as post-transplant maintenance therapy for high-risk acute myeloid leukemia and myelodysplastic syndrome. Cancer Sci. 2021; 112: 3636-3644. – reference: 30. Pfeifer H, Wassmann B, Bethge W, et al. GMALL Study Group. Randomized comparison of prophylactic and minimal residual disease-triggered imatinib after allogeneic stem cell transplantation for BCR- ABL1-positive acute lymphoblastic leukemia. Leukemia. 2013; 27: 1254-1262. – reference: 33. Jabbour E, Giralt S, Kantarjian H, et al. Low-dose azacitidine after allogeneic stem cell transplantation for acute leukemia. Cancer. 2009; 115: 1899-1905. – reference: 41. de Lima M, Oran B, Champlin RE, et al. CC-486 Maintenance after Stem Cell Transplantation in Patients with Acute Myeloid Leukemia or Myelodysplastic Syndromes. Biol Blood Marrow Transplant. 2018; 24: 2017-2024. – reference: 45. Zhao Y, Aldoss I, Qu C, et al. Tumor-intrinsic and-extrinsic determinants of response to blinatumomab in adults with B-ALL. Blood. 2021; 137: 471-484. – reference: 10. Helbig G, Koclęga A, Wieczorkiewicz-Kabut A, et al. Pre-transplant FLT3/ITD status predicts outcome in FLT3-mutated acute myeloid leukemia following allogeneic stem cell transplantation. Ann Hematol. 2020; 99: 1845-1853. – reference: 43. Gaballa MR, Banerjee P, Milton DR, et al. Blinatumomab maintenance after allogeneic hematopoietic cell transplantation for B-lineage acute lymphoblastic leukemia. Blood. 2022; 139: 1908-1919. – reference: 31. Warraich Z, Tenneti P, Thai T, et al. Relapse Prevention with Tyrosine Kinase Inhibitors after Allogeneic Transplantation for Philadelphia Chromosome-Positive Acute Lymphoblast Leukemia: A Systematic Review. Biol Blood Marrow Transplant. 2020; 26: e55-e64. – reference: 14. Brunner AM, Li S, Fathi AT, et al. 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| Snippet | 造血細胞移植後の再発は，現代の移植医療が解決すべき最重要課題のひとつである。この10年間，ゲノミクスの進歩を背景として新しい抗腫瘍薬開発が着実に進... |
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| SubjectTerms | allogeneic hematopoietic stem cell transplantation minimal residual disease post-transplant relapse posttransplant maintenance therapy |
| Title | 移植後維持療法の現在と将来展望 |
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