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Treatment of Adult T-Cell Leukemia/Lymphoma: Established Paradigms and Emerging Directions

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Opinion Statement

Adult T-cell leukemia/lymphoma (ATL) is a rare, aggressive subtype of peripheral T-cell lymphoma developing after many years of chronic, asymptomatic infection with the retrovirus human T-cell lymphotropic virus type 1 (HTLV-1). HTLV-1 is endemic to certain geographic areas of the world, and primary infection generally occurs in infancy through mother-to-child transmission via breastfeeding. In less than 5% of infected individuals, a decades-long pathogenic process culminates in the development of ATL. Aggressive subtypes of ATL are life-threatening and challenging to treat, with median overall survival typically less than 1 year in the absence of allogeneic hematopoietic cell transplantation (alloHCT). Owing to the rarity of this illness, prospective large-scale clinical trials have been challenging to perform, and treatment recommendations are largely founded upon limited evidence. Herein, we review the current therapeutic options for ATL, providing a broad literature overview of the foremost clinical trials and reports of this disease. We emphasize our own treatment paradigm, which is broadly based upon disease subtype, patient fitness, and intent to perform alloHCT. Finally, we highlight recent advances in understanding ATL disease biology and important ongoing clinical trials that we foresee as informative and potentially practice-changing.

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References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Gessain A, Cassar O. Epidemiological aspects and world distribution of HTLV-1 Infection. Front Microbiol. 2012;3:388.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Gonçalves DU, Proietti FA, Ribas JGR, et al. Epidemiology, treatment, and prevention of human T-cell leukemia virus type 1-associated diseases. Clin Microbiol Rev. 2010;23(3):577–89.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Cook LB, Rowan AG, Melamed A, Taylor GP, Bangham CRM. HTLV-1–infected T cells contain a single integrated provirus in natural infection. Blood. 2012;120(17):3488–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Schierhout G, McGregor S, Gessain A, et al. Association between HTLV-1 infection and adverse health outcomes: a systematic review and meta-analysis of epidemiological studies. Lancet Infect Dis. 2020;20(1):133–43.

    Article  CAS  PubMed  Google Scholar 

  5. Iwanaga M, Watanabe T, Utsunomiya A, et al. Human T-cell leukemia virus type I (HTLV-1) proviral load and disease progression in asymptomatic HTLV-1 carriers: a nationwide prospective study in Japan. Blood. 2010;116(8):1211–9.

    Article  CAS  PubMed  Google Scholar 

  6. Demontis MA, Hilburn S, Taylor GP. Human T cell lymphotropic virus type 1 viral load variability and long-term trends in asymptomatic carriers and in patients with human T cell lymphotropic virus type 1-related diseases. AIDS Res Hum Retroviruses. 2013;29(2):359–64.

    Article  CAS  PubMed  Google Scholar 

  7. Suzumiya J, Ohshima K, Tamura K, et al. The International Prognostic Index predicts outcome in aggressive adult T-cell leukemia/lymphoma: analysis of 126 patients from the International Peripheral T-Cell Lymphoma Project. Ann Oncol. 2009;20(4):715–21.

    Article  CAS  PubMed  Google Scholar 

  8. Iwanaga M. Epidemiology of HTLV-1 Infection and ATL in Japan: an update. Front Microbiol. 2020;11:1124.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Shah UA, Shah N, Qiao B, et al. Epidemiology and survival trend of adult T-cell leukemia/lymphoma in the United States. Cancer. 2020;126(3):567–74.

    Article  PubMed  Google Scholar 

  10. Rowan AG, Dillon R, Witkover A, et al. Evolution of retrovirus-infected premalignant T-cell clones prior to adult T-cell leukemia/lymphoma diagnosis. Blood. 2020;135(23):2023–32.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Yamagishi M, Kubokawa M, Kuze Y, et al. Chronological genome and single-cell transcriptome integration characterizes the evolutionary process of adult T cell leukemia-lymphoma. Nat Commun. 2021;12(1):1–16.

    Article  Google Scholar 

  12. Shimoyama M. Diagnostic criteria and classification of clinical subtypes of adult T-cell leukaemia-lymphoma. A report from the Lymphoma Study Group (1984-87). Br J Haematol. 1991;79(3):428–37.

    Article  CAS  PubMed  Google Scholar 

  13. Katsuya H, Ishitsuka K, Utsunomiya A, et al. Treatment and survival among 1594 patients with ATL. Blood. 2015;126(24):2570–7.

    Article  CAS  PubMed  Google Scholar 

  14. Bittencourt AL, Vieira MDG, Brites CR, Farre L, Barbosa HS. Adult T-cell leukemia/lymphoma in Bahia, Brazil: analysis of prognostic factors in a group of 70 patients. Am J Clin Pathol. 2007;128(5):875–82.

    Article  PubMed  Google Scholar 

  15. Tsukasaki K, Hermine O, Bazarbachi A, et al. Definition, prognostic factors, treatment, and response criteria of adult T-cell leukemia-lymphoma: a proposal from an international consensus meeting. J Clin Oncol. 2009;27(3):459.

    Article  Google Scholar 

  16. Valcarcel B, Sano H, Katsuya H, et al. Clinical features, treatment patterns, and outcomes among 837 patients with adult T-cell leukemia-lymphoma in the real-world setting: a comparison of endemic regions. Blood. 2022;140(Supplement 1):1072–3.

    Article  Google Scholar 

  17. Tsukasaki K, Tobinai K, Shimoyama M, et al. Deoxycoformycin-containing combination chemotherapy for adult T-cell leukemia-lymphoma: Japan Clinical Oncology Group Study (JCOG9109). Int J Hematol. 2003;77(2):164–70.

    Article  CAS  PubMed  Google Scholar 

  18. Yamada Y, Tomonaga M, Fukuda H, et al. A new G-CSF-supported combination chemotherapy, LSG15, for adult T-cell leukaemia-lymphoma: Japan Clinical Oncology Group Study 9303. Br J Haematol. 2001;113(2):375–82.

    Article  CAS  PubMed  Google Scholar 

  19. Tsukasaki K, Utsunomiya A, Fukuda H, et al. VCAP-AMP-VECP compared with biweekly CHOP for adult T-cell leukemia-lymphoma: Japan Clinical Oncology Group study JCOG9801. J Clin Oncol. 2007;25(34):5458–64.

    Article  CAS  PubMed  Google Scholar 

  20. Alduaij A, Butera JN, Treaba D, Castillo J. Complete remission in two cases of adult T-Cell Leukemia/Lymphoma treated with Hyper-CVAD: a case report and review of the literature. Clin Lymphoma Myeloma Leuk. 2010;10(6):480–3.

    Article  PubMed  Google Scholar 

  21. Ratner L, Rauch D, Abel H, et al. Dose-adjusted EPOCH chemotherapy with bortezomib and raltegravir for human T-cell leukemia virus-associated adult T-cell leukemia lymphoma. Blood Cancer J. 2016;6(3):e408.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Ratner L, Harrington W, Feng X, et al. Human T cell leukemia virus reactivation with progression of adult T-cell leukemia-lymphoma. PLoS One. 2009;4(2):e4420.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Malpica L, Pimentel A, Reis IM, et al. Epidemiology, clinical features, and outcome of HTLV-1–related ATLL in an area of prevalence in the United States. Blood Adv. 2018;2(6):607–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Toriyama E, Imaizumi Y, Taniguchi H, et al. EPOCH regimen as salvage therapy for adult T-cell leukemia-lymphoma. Int J Hematol. 2018;108(2):167–75.

    Article  CAS  PubMed  Google Scholar 

  25. Maeda Y, Nishimori H, Yoshida I, et al. Dose-adjusted EPOCH chemotherapy for untreated peripheral T-cell lymphomas: a multicenter phase II trial of West-JHOG PTCL0707. Haematologica. 2017;102(12):2097–103.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Schmitz N, Trümper L, Ziepert M, et al. Treatment and prognosis of mature T-cell and NK-cell lymphoma: an analysis of patients with T-cell lymphoma treated in studies of the German High-Grade Non-Hodgkin Lymphoma Study Group. Blood. 2010;116(18):3418–25.

    Article  CAS  PubMed  Google Scholar 

  27. Escalón MP, Liu NS, Yang Y, et al. Prognostic factors and treatment of patients with T-cell non-Hodgkin lymphoma: the M. D. Anderson Cancer Center experience. Cancer. 2005;103(10):2091–8.

    Article  PubMed  Google Scholar 

  28. Phillips AA, Shapira I, Willim RD, et al. A critical analysis of prognostic factors in North American patients with human T-cell lymphotropic virus type-1-associated adult T-cell leukemia/lymphoma: a multicenter clinicopathologic experience and new prognostic score. Cancer. 2010;116(14):3438–46.

    Article  PubMed  Google Scholar 

  29. Horwitz S, O’Connor OA, Pro B, et al. Brentuximab vedotin with chemotherapy for CD30-positive peripheral T-cell lymphoma (ECHELON-2): a global, double-blind, randomised, phase 3 trial. Lancet. 2019;393(10168):229–40.

    Article  CAS  PubMed  Google Scholar 

  30. Dittus C, Weinstock MJ, Barnes JA, et al. Interim results of a multicenter pilot study evaluating brentuximab vedotin with cyclophosphamide, doxorubicin, etoposide, and prednisone (BV-CHEP) for the treatment of aggressive adult T-cell leukemia/lymphoma. Blood. 2021;138(Supplement 1):1395–5.

    Article  Google Scholar 

  31. Herrera AF, Zain J, Savage KJ, et al. Brentuximab vedotin plus cyclophosphamide, doxorubicin, etoposide, and prednisone (CHEP-BV) followed by BV consolidation in patients with CD30-Expressing Peripheral T-Cell Lymphomas. Blood. 2021;138(Supplement 1):133–3.

    Article  Google Scholar 

  32. Hodson A, Crichton S, Montoto S, et al. Use of zidovudine and interferon alfa with chemotherapy improves survival in both acute and lymphoma subtypes of adult T-cell leukemia/lymphoma. J Clin Oncol. 2011;29(35):4696–701.

    Article  CAS  PubMed  Google Scholar 

  33. Cook LB, Phillips AA. How I treat adult T-cell leukemia/lymphoma. Blood. 2021;137(4):459–70.

    Article  CAS  PubMed  Google Scholar 

  34. Tanimoto K, Kato K, Aoki T, et al. CHOP plus sequential mogamulizumab as first-line therapy for untreated adult T-cell leukemia-lymphoma. Blood. 2021;138(Supplement 1):1393–3.

    Article  Google Scholar 

  35. Ishida T, Jo T, Takemoto S, et al. Dose-intensified chemotherapy alone or in combination with mogamulizumab in newly diagnosed aggressive adult T-cell leukaemia-lymphoma: A randomized phase II study. Br J Haematol. 2015;169(5):672–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Ishida T, Jo T, Takemoto S, et al. Follow-up of a randomised phase II study of chemotherapy alone or in combination with mogamulizumab in newly diagnosed aggressive adult T-cell leukaemia-lymphoma: impact on allogeneic haematopoietic stem cell transplantation. Br J Haematol. 2019;184(3):479–83.

    Article  PubMed  Google Scholar 

  37. Jo T, Matsuzaka K, Shioya H, et al. Mogamulizumab plus EPOCH therapy for patients with newly diagnosed aggressive adult T-cell leukemia/lymphoma. Anticancer Res. 2020;40(9):5237–43.

    Article  CAS  PubMed  Google Scholar 

  38. Sugio T, Kato K, Aoki T, et al. Mogamulizumab treatment prior to allogeneic hematopoietic stem cell transplantation induces severe acute graft-versus-host disease. Biol Blood Marrow Transplant. 2016;22(9):1608–14.

    Article  CAS  PubMed  Google Scholar 

  39. Fuji S, Inoue Y, Utsunomiya A, et al. Pretransplantation anti-CCR4 antibody mogamulizumab against adult T-cell leukemia/lymphoma is associated with significantly increased risks of severe and corticosteroid-refractory graft-versus-host disease, nonrelapse mortality, and overall mortality. J Clin Oncol. 2016;34(28):3426–33.

    Article  PubMed  Google Scholar 

  40. Inoue Y, Fuji S, Tanosaki R, Fukuda T. Pretransplant mogamulizumab against ATLL might increase the risk of acute GVHD and non-relapse mortality. Bone Marrow Transplant. 2016;51(5):725–7.

    Article  CAS  PubMed  Google Scholar 

  41. Haji S, Kiyasu J, Choi I, et al. Administration of an anti-CC chemokine receptor 4 monoclonal antibody, mogamulizumab, before allogeneic bone marrow transplantation for adult T-cell leukemia/lymphoma. Bone Marrow Transplant. 2016;51(3):432–4.

    Article  CAS  PubMed  Google Scholar 

  42. Bazarbachi A, Plumelle Y, Ramos JC, et al. Meta-analysis on the use of zidovudine and interferon-alfa in adult T-cell leukemia/lymphoma showing improved survival in the leukemic subtypes. J Clin Oncol. 2010;28(27):4177–83.

    Article  CAS  PubMed  Google Scholar 

  43. Sakamoto Y, Ishida T, Masaki A, et al. Clinical significance of TP53 mutations in adult T-cell leukemia/lymphoma. Br J Haematol. 2021;195(4):571–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Sakamoto Y, Ishida T, Masaki A, et al. Clinicopathological significance of CD28 overexpression in adult T-cell leukemia/lymphoma. Cancer Sci. 2022;113(1):349–61.

    Article  CAS  PubMed  Google Scholar 

  45. Sakamoto Y, Ishida T, Masaki A, et al. Clinical significance of CD28 gene-related activating alterations in adult T-cell leukaemia/lymphoma. Br J Haematol. 2021;192(2):281–91.

    Article  CAS  PubMed  Google Scholar 

  46. Nakahata S, Morishita K. The role of CD28 in adult T-cell leukaemia/lymphoma. Br J Haematol. 2021;192(2):235–6.

    Article  CAS  PubMed  Google Scholar 

  47. Horwitz SM, Ansell S, Ai WZ, et al. T-Cell Lymphomas, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2022;20(3):285–308.

    Article  CAS  PubMed  Google Scholar 

  48. Fox CP, Ahearne MJ, Pettengell R, et al. Guidelines for the management of mature T- and natural killer-cell lymphomas (excluding cutaneous T-cell lymphoma): a British Society for Haematology Guideline. Br J Haematol. 2022;196(3):507–22.

    Article  PubMed  Google Scholar 

  49. Cook LB, Fuji S, Hermine O, et al. Revised adult T-cell leukemia-lymphoma international consensus meeting report. J Clin Oncol. 2019;37(8):677–87.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Fuji S, Fujiwara H, Nakano N, et al. Early application of related SCT might improve clinical outcome in adult T-cell leukemia/lymphoma. Bone Marrow Transplant. 2016;51:2. 2015;51(2):205–11.

    Article  Google Scholar 

  51. Bazarbachi A, Cwynarski K, Boumendil A, et al. Outcome of patients with HTLV-1-associated adult T-cell leukemia/lymphoma after SCT: a retrospective study by the EBMT LWP. Bone Marrow Transplant. 2014;49(10):1266–8.

    Article  CAS  PubMed  Google Scholar 

  52. Fuji S, Yamaguchi T, Inoue Y, et al. Development of a modified prognostic index for patients with aggressive adult T-cell leukemia-lymphoma aged 70 years or younger: possible risk-adapted management strategies including allogeneic transplantation. Haematologica. 2017;102(7):1265.

    Article  Google Scholar 

  53. Hishizawa M, Kanda J, Utsunomiya A, et al. Transplantation of allogeneic hematopoietic stem cells for adult T-cell leukemia: a nationwide retrospective study. Blood. 2010;116(8):1369–76.

    Article  CAS  PubMed  Google Scholar 

  54. Fukushima T, Miyazaki Y, Honda S, et al. Allogeneic hematopoietic stem cell transplantation provides sustained long-term survival for patients with adult T-cell leukemia/lymphoma. Leukemia. 2005;19(5):829–34.

    Article  CAS  PubMed  Google Scholar 

  55. Kami M, Hamaki T, Miyakoshi S, et al. Allogeneic haematopoietic stem cell transplantation for the treatment of adult T-cell leukaemia/lymphoma. Br J Haematol. 2003;120(2):304–9.

    Article  PubMed  Google Scholar 

  56. Utsunomiya A, Miyazaki Y, Takatsuka Y, et al. Improved outcome of adult T cell leukemia/lymphoma with allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplantation. 2001;27(1):15–20.

    Article  CAS  PubMed  Google Scholar 

  57. Epstein-Peterson ZD, Ganesan N, Barker JN, et al. Outcomes of adult T-Cell leukemia/lymphoma with allogeneic stem cell transplantation: single-institution experience. Leuk Lymphoma. 2021;62(9):2177–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Ito A, Nakano N, Tanaka T, et al. Improved survival of patients with aggressive ATL by increased use of allo-HCT: a prospective observational study. Blood Adv. 2021;5(20):4156–66.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. • Iqbal M, Reljic T, Klocksieben F, et al. Efficacy of allogeneic hematopoietic cell transplantation in human T cell lymphotropic virus type 1-associated adult T cell leukemia/lymphoma: results of a systematic review/meta-analysis. Biol Blood Marrow Transplant. 2019;25(8):1695–700. Meta-Analysis of allogenetic transplant in ATL.

    Article  PubMed  Google Scholar 

  60. Matsushita K, Matsumoto T, Ohtsubo H, et al. Long-term maintenance combination chemotherapy with OPEC/MPEC (vincristine or methotrexate, prednisolone, etoposide and cyclophosphamide) or with daily oral etoposide and prednisolone can improve survival and quality of life in adult T-cell leukemia/lymphoma. Leuk Lymphoma. 1999;36(1–2):67–75.

    Article  CAS  PubMed  Google Scholar 

  61. Takasaki Y, Iwanaga M, Imaizumi Y, et al. Long-term study of indolent adult T-cell leukemia-lymphoma. Blood. 2010;115(22):4337–43.

    Article  CAS  PubMed  Google Scholar 

  62. Gill PS, Harrington W, Kaplan MH, et al. Treatment of adult T-cell leukemia-lymphoma with a combination of interferon alfa and zidovudine. N Engl J Med. 1995;332(26):1744–8.

    Article  CAS  PubMed  Google Scholar 

  63. Hermine O, Bouscary D, Gessain A, et al. Brief report: treatment of adult T-cell leukemia-lymphoma with zidovudine and interferon alfa. N Engl J Med. 1995;332(26):1749–51.

    Article  CAS  PubMed  Google Scholar 

  64. White JD, Wharfe G, Stewart DM, et al. The combination of zidovudine and interferon aipha-2B in the treatment of adult T-cell leukemia/lymphoma. Leuk Lymphoma. 2001;40(42067):287–94.

    Article  CAS  PubMed  Google Scholar 

  65. Hermine O, Allard I, Lévy V, et al. A prospective phase II clinical trial with the use of zidovudine and interferon-alpha in the acute and lymphoma forms of adult T-cell leukemia/lymphoma. Hematol J. 2002;3(6):276–82.

    Article  CAS  PubMed  Google Scholar 

  66. Kinpara S, Kijiyama M, Takamori A, et al. Interferon-α (IFN-α) suppresses HTLV-1 gene expression and cell cycling, while IFN-α combined with zidovudine induces p53 signaling and apoptosis in HTLV-1-infected cells. Retrovirology. 2013;10(1):52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Datta A, Bellon M, Sinha-Datta U, et al. Persistent inhibition of telomerase reprograms adult T-cell leukemia to p53-dependent senescence. Blood. 2006;108(3):1021–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Tsukasaki K, Imaizumi Y, Tokura Y, et al. Meeting report on the possible proposal of an extranodal primary cutaneous variant in the lymphoma type of adult T-cell leukemia-lymphoma. J Dermatol. 2014;41(1):26–8.

    Article  PubMed  Google Scholar 

  69. Sawada Y, Hino R, Hama K, et al. Type of skin eruption is an independent prognostic indicator for adult T-cell leukemia/lymphoma. Blood. 2011;117(15):3961–7.

    Article  CAS  PubMed  Google Scholar 

  70. O’Connor OA, Pro B, Pinter-Brown L, et al. Pralatrexate in patients with relapsed or refractory peripheral T-cell lymphoma: results from the pivotal PROPEL study. J Clin Oncol. 2011;29(9):1182–9.

    Article  PubMed  PubMed Central  Google Scholar 

  71. O’Connor OA, Horwitz S, Masszi T, et al. Belinostat in patients with relapsed or refractory peripheral T-cell lymphoma: results of the pivotal phase II BELIEF (CLN-19) Study. J Clin Oncol. 2015;33(23):2492–9.

    Article  PubMed  PubMed Central  Google Scholar 

  72. Coiffier B, Pro B, Prince HM, et al. Results from a pivotal, open-label, phase II study of romidepsin in relapsed or refractory peripheral T-cell lymphoma after prior systemic therapy. J Clin Oncol. 2012;30(6):631–6.

    Article  CAS  PubMed  Google Scholar 

  73. Yamamoto K, Utsunomiya A, Tobinai K, et al. Phase I study of KW-0761, a defucosylated humanized anti-CCR4 antibody, in relapsed patients with adult T-cell leukemia-lymphoma and peripheral T-cell lymphoma. J Clin Oncol. 2010;28(9):1591–8.

    Article  CAS  PubMed  Google Scholar 

  74. Ishida T, Joh T, Uike N, et al. Defucosylated anti-CCR4 monoclonal antibody (KW-0761) for relapsed adult T-cell leukemia-lymphoma: a multicenter phase II study. J Clin Oncol. 2012;30(8):837–42.

    Article  CAS  PubMed  Google Scholar 

  75. Ishitsuka K, Yurimoto S, Tsuji Y, et al. Safety and effectiveness of mogamulizumab in relapsed or refractory adult T-cell leukemia-lymphoma. Eur J Haematol. 2019;102(5):407–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Ishida T, Utsunomiya A, Jo T, et al. Mogamulizumab for relapsed adult T-cell leukemia-lymphoma: Updated follow-up analysis of phase I and II studies. Cancer Sci. 2017;108(10):2022–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Hirotsu KE, Neal TM, Khodadoust MS, et al. Clinical characterization of mogamulizumab-associated rash during treatment of mycosis fungoides or Sézary Syndrome. JAMA Dermatol. 2021;157(6):700–7.

    Article  PubMed  Google Scholar 

  78. de Masson A, Darbord D, Dobos G, et al. Macrophage-derived CXCL9 and CXCL11, T-cell skin homing, and disease control in mogamulizumab-treated CTCL patients. Blood. 2022;139(12):1820–32.

    Article  PubMed  Google Scholar 

  79. • Phillips AA, Fields PA, Hermine O, et al. Mogamulizumab versus investigator’s choice of chemotherapy regimen in relapsed/refractory adult T-cell leukemia/lymphoma. Haematologica. 2019;104(5):993–1003. Randomized trial of mogamulizumab versus investigator’s choice in R/R ATL outside of Asia.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Sakamoto Y, Ishida T, Masaki A, et al. CCR4 mutations associated with superior outcome of adult T-cell leukemia/lymphoma under mogamulizumab treatment. Blood. 2018;132(7):758–61.

    Article  PubMed  Google Scholar 

  81. Sakamoto Y, Ishida T, Masaki A, et al. CCR7 alterations associated with inferior outcome of adult T-cell leukemia/lymphoma under mogamulizumab treatment. Hematol Oncol. 2022;40(5):876–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Tanaka N, Mori S, Kiyotani K, et al. Genomic determinants impacting the clinical outcome of mogamulizumab treatment for adult T-cell leukemia/lymphoma. Haematologica. 2022;107(10):2418–31.

    Article  PubMed  PubMed Central  Google Scholar 

  83. Beygi S, Duran GE, Fernandez-Pol S, et al. Resistance to mogamulizumab is associated with loss of CCR4 in cutaneous T-cell lymphoma. Blood. 2022;139(26):3732–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Sakamoto H, Itonaga H, Sawayama Y, et al. Treatment with mogamulizumab or lenalidomide for relapsed adult T-cell leukemia/lymphoma after allogeneic hematopoietic stem cell transplantation: The Nagasaki transplant group experience. Hematol Oncol. 2020;38(2):162–70.

    Article  CAS  PubMed  Google Scholar 

  85. Ishida T, Fujiwara H, Nosaka K, et al. Multicenter phase II study of lenalidomide in relapsed or recurrent adult T-cell leukemia/lymphoma: ATLL-002. J Clin Oncol. 2016;34(34):4086–93.

    Article  CAS  PubMed  Google Scholar 

  86. Phillips AA, Giddings J, Lee SM, Horwitz SM. Lenalidomide in patients with Relapsed or Refractory HTLV-1 Related Adult T cell Leukemia/Lymphoma (ATLL). Int J Blood Res Disord. 2015;2:3.

    Article  Google Scholar 

  87. Lunning MA, Gonsky J, Ruan J, et al. Pralatrexate in relapsed/refractory HTLV-1 associated adult T-cell lymphoma/leukemia: a New York City Multi-Institutional Experience. Blood. 2012;120(21):2735.

    Article  Google Scholar 

  88. Mukhi N, Verma V, Ahmed A, et al. Romidepsin in relapsed/refractory HTLV-1 associated adult T-cell lymphoma/leukemia: a case series. Blood. 2015;126(23):5113.

    Article  Google Scholar 

  89. Ishitsuka K, Utsunomiya A, Katsuya H, et al. A phase II study of bortezomib in patients with relapsed or refractory aggressive adult T-cell leukemia/lymphoma. Cancer Sci. 2015;106(9):1219–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Ishitsuka K, Suzumiya J, Aoki M, et al. Therapeutic potential of arsenic trioxide with or without interferon-α for relapsed/refractory adult T-cell leukemia/lymphoma. Haematologica. 2007;92(5):719–20.

    Article  CAS  PubMed  Google Scholar 

  91. Hermine O, Dombret H, Poupon J, et al. Phase II trial of arsenic trioxide and alpha interferon in patients with relapsed/refractory adult T-cell leukemia/lymphoma. Hematol J. 2004;5(2):130–4.

    Article  CAS  PubMed  Google Scholar 

  92. Sharma K, Janik JE, O’Mahony D, et al. Phase II Study of Alemtuzumab (CAMPATH-1) in Patients with HTLV-1-Associated Adult T-cell Leukemia/lymphoma. Clin Cancer Res. 2017;23(1):35–42.

    Article  CAS  PubMed  Google Scholar 

  93. Utsunomiya A, Izutsu K, Jo T, et al. Oral histone deacetylase inhibitor tucidinostat (HBI-8000) in patients with relapsed or refractory adult T-cell leukemia/lymphoma: Phase IIb results. Cancer Sci. 2022;113(8):2778.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Iyer SP, Sica RA, Ho PJ, et al. S262: The Cobalt-LYM Study of CTX130: a phase I dose escalation study of CD70-targeted allogeneic CRISPR-CAS9-engineered CAR T cells in patients with relapsed/refractory (R/R) T-cell malignancies. Hemasphere. 2022;6:163–4.

    Article  Google Scholar 

  95. Pongas G, Toomey NL, Reis IM, et al. Safety and efficacy of belinostat trial with zidovudine plus interferon for HTLV-1 related adult T-cell leukemia-lymphoma: interim results. Blood. 2022;140(Supplement 1):9448–9.

    Article  Google Scholar 

  96. Daenthanasanmak A, Bamford RN, Yoshioka M, et al. Triple combination of BET plus PI3K and NF-κB inhibitors exhibit synergistic activity in adult T-cell leukemia/lymphoma. Blood Adv. 2022;6(7):2346–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Ishio T, Kumar S, Shimono J, et al. Genome-wide CRISPR screen identifies CDK6 as a therapeutic target in adult T-cell leukemia/lymphoma. Blood. 2022;139(10):1541–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Daenthanasanmak A, Lin Y, Zhang M, et al. Enhanced efficacy of JAK1 inhibitor with mTORC1/C2 targeting in smoldering/chronic adult T cell leukemia. Transl Oncol. 2021;14(1):100913.

    Article  CAS  PubMed  Google Scholar 

  99. Shi M, Shahsafaei A, Liu C, Yu H, Dorfman DM. Enhancer of zeste homolog 2 is widely expressed in T-cell neoplasms, is associated with high proliferation rate and correlates with MYC and pSTAT3 expression in a subset of cases. Leuk Lymphoma. 2015;56(7):2087–91.

    Article  CAS  PubMed  Google Scholar 

  100. Simon C, Chagraoui J, Krosl J, et al. A key role for EZH2 and associated genes in mouse and human adult T-cell acute leukemia. Genes Dev. 2012;26(7):651–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. • Izutsu K, Makita S, Nosaka K, et al. An Open-Label, Single-Arm, Phase 2 Trial of Valemetostat in Relapsed or Refractory Adult T-Cell Leukemia/Lymphoma. Blood. 2022;Sep 23(blood.2022016862.). Phase 2 trial of valemetostat in R/R ATL, leading to approval in Japan.

  102. Ishitsuka K, Izutsu K, Maruyama D, et al. First inhuman study of the EZH1 and EZH2 dual inhibitor valemetostat (DS-3201B) in patients with relapsed or refractory non-Hodgkin lymphoma. Hematol Oncol. 2021;39(S2):Abstract S218.

  103. Kataoka K, Nagata Y, Kitanaka A, et al. Integrated molecular analysis of adult T cell leukemia/lymphoma. Nat Genet. 2015;47(11):1304–15.

    Article  CAS  PubMed  Google Scholar 

  104. Kogure Y, Kameda T, Koya J, et al. Whole-genome landscape of adult T-cell leukemia/lymphoma. Blood. 2022;139(7):967–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Lymphoma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, 530 E. 74th St, New York, NY, 10021, USA

    Robert Stuver MD, Steven M. Horwitz MD & Zachary D. Epstein-Peterson MD

  2. Department of Medicine, Weill Cornell Medical College, New York, NY, USA

    Steven M. Horwitz MD & Zachary D. Epstein-Peterson MD

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  1. Robert Stuver MD
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Correspondence to Robert Stuver MD.

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Stuver, R., Horwitz, S.M. & Epstein-Peterson, Z.D. Treatment of Adult T-Cell Leukemia/Lymphoma: Established Paradigms and Emerging Directions. Curr. Treat. Options in Oncol. 24, 948–964 (2023). https://doi.org/10.1007/s11864-023-01111-1

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