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Adrienne A. Phillips et al.
Treatment-related AEs grade ≥3 were infrequent. Comparison of mogamulizumab and investigator’s choice arms revealed little difference in the overall incidence of treatment-related AEs of any grade or grade ≥3 despite the fact that the duration of treatment exposure was approxi- mately 3-fold longer in the mogamulizumab arm.
In summary, we have conducted the first, prospective, randomized therapeutic trial of ATL outside Japan. Because of the rarity of the disease, the study required a major collaborative effort across multiple international centers to achieve the target accrual within 3 years. Despite small numbers and unbalanced randomization, the trial demonstrated the efficacy of mogamulizumab (e.g. PFS, ORR, responses observed after crossover, dura- bility of responses) in comparison to other frequently used agents. The safety profile in this ethnically diverse patient population with a high unmet medical need was manage- able, while minimal benefit was demonstrated with com- monly used chemotherapy agents. Given the rates of best response but overall short duration and PFS for many patients with this aggressive disease, future studies should explore combinations with other agents. For example, lenalidomide has demonstrated single agent activity and
may potentiate ADCC in other non-Hodgkin lymphoma subtypes.31,40 Earlier lines of therapy, prior to the relapsed/refractory setting, where there is greater possibil- ity of impacting the disease course should also be investi- gated.
Funding
This study was supported by Kyowa Kirin (Princeton, NJ, USA). We thank the investigators and co-ordinators at each of the participating study centers, the patients who volunteered to participate in this study and their families, and the sponsor staff involved in data collection and analyses. Peter Todd (Tajut Ltd., Kaiapoi, New Zealand) provided editorial assistance in the development of the manuscript, for which he received financial compensation from Kyowa Kirin (Princeton, NJ, USA). The authors had complete access to all data and maintained control over the manuscript, including final wording and conclusions. AP was, in part, supported by The Harold Amos Medical Faculty Development Program (Robert Wood Johnson Foundation) for this research and career development. Researchers at the Memorial-Sloan Kettering Cancer Center were funded, in part, through the NIH/NCI Cancer Center Support Grant P30 CA008748.
References
1. Uchiyama T, Yodoi J, Sagawa K, et al. Adult T-cell leukemia: clinical and hematologic features of 16 cases. Blood. 1977; 50(30):481-492.
2. Poiesz BJ, Ruscetti FW, Gazdar AF, et al. Detection and isolation of type C retrovirus particles from fresh and cultured lympho- cytes of a patient with cutaneous T-cell lymphoma. Proc Natl Acad Sci U S A. 1980; 77(12):7415-7419.
3. Hinuma Y, Nagata K, Hanaoka M, et al. Adult T-cell leukemia: Antigen in an ATL cell line and detection of antibodies to the antigen in human sera. Proc Natl Acad Sci U S A. 1981;78(10):6476-6480.
4. Yoshida M, Miyoshi I, Hinuma Y. Isolation and characterization of retrovirus from cell lines of human adult T-cell leukemia and its implication in the disease. Proc Natl Acad Sci U S A. 1982;79(6):2031-2035.
5. Vose J, Armitage J, Weisenburger D; International T-Cell Lymphoma Project: International peripheral T-cell and natural killer/T-cell lymphoma study. Pathology findings and clinical outcomes. J Clin Oncol. 2008;26(25):4124-4130.
6. Iwanaga M, Watanabe T, Yamaguchi K. Adult T-cell leukemia: a review of epidemi- ological evidence. Front Microbiol. 2012;3:322.
7. IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Human immunodeficiciency viruses and human T- cell lymphotropic viruses. IARC Monogr Eval Carcinog Risks Hum. 1996;67:1-424.
8. Gessain A, Cassar O. Epidemiological aspects and world distribution on HTLV-1 infection. Front Microbiol. 2012;3:388.
9. Proietti FA, Carneiro-Proietti ABF, Catalan- Soares BC, et al. Global epidemiology of HTLV-I infection and associated diseases. Oncogene. 2005;24(39):6058-6068.
10. Yoshida N, Chihara D. Incidence of adult T-cell leukemia/lymphoma in nonendemic
areas. Curr Treat Options Oncol. 2015;
16(2):7.
11. Chihara D, Ito H, Matsuda T, et al.
Differences in incidence and trends of haematological malignancies in Japan and the United States. Br J Haematol. 2014; 164(4):536-545.
12. Shimoyama M. Diagnostic criteria and clas- sification of clinical subtypes of adult T-cell leukaemia-lymphoma. A report from the Lymphoma Study Group (1984-87). Br J Haematol. 1991;79(3):428-437.
13. 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):5458-5464.
14. Takasaki Y, Iwanaga M, Imaizumi Y, et al. Long-term study of indolent adult T-cell leukemia-lymphoma. Blood. 2010; 115(22):4337-4343
15. Phillips AA, Shapira I, Willims 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 multi- center clinicopathologic experience and new prognostic score. Cancer. 2010; 116(14):3438-3446.
16. 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):1369-1376.
17. Ishida T, Hishizawa M, Kato K, et al. Allogeneic hematopoietic stem cell trans- plantation for adult T-cell leukemia-lym- phoma with special emphasis on precondi- tioning regimen: a nationwide retrospec- tive study. Blood. 2012;120(8):1734-1741.
18. Fujiwara H, Fuji S, Wake A, et al; ATL Working Group of the Japan Society for Hematopoietic Cell Transplantation. Dismal outcome of allogeneic hematopoi- etic stem cell transplantation for relapsed
adult T-cell leukemia/lymphoma, a Japanese nation-wide study. Bone Marrow Transplant. 2017;52(3):484-488.
19. Yoshie O, Fujisawa R, Nakayama T, et al. Frequent expression of CCR4 in adult T-cell leukemia and human T-cell leukemia virus type-1 transformed T-cells. Blood. 2002; 99(5):1505-1511.
20. Ishida T, Utsunomiya A, Iida S, et al. Clinical significance of CCR4 expression in adult T-cell leukemia/lymphoma: Its close association with skin involvement and unfavorable outcome. Clin Cancer Res. 2003;9(10):3625-3634.
21. Ishii T, Ishida T, Utsunomiya A, et al. Defucosylated humanized anti-CCR4 monoclonal antibody KW-0761 as a novel immunotherapeutic agent for adult T-cell leukemia/lymphoma. Clin Cancer Res. 2010;16(5):1520-1531.
22. 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):837-842.
23. Ishida T, Jo T, Takemoto S, et al. Dose- intensified chemotherapy alone or in com- bination with mogamulizumab in newly diagnosed aggressive adult T-cell leukaemia-lymphoma: a randomized phase II study. Br J Haematol. 2015;169(5):672- 682.
24. O’Connor OA, Horwitz S, Hamlin P, et al. Phase II-I-II Study of two different doses and schedules of pralatrexate, a high-affini- ty substrate for the reduced folate carrier, in patients with relapsed or refractory lym- phoma reveals marked activity in T-cell malignancies. J Clin Oncol. 2009; 27(26):4357-4364.
25. Tsukasaki K, Hermine O, Bazarbachi A, et al. Definition, prognostic factors, treat- ment, and response criteria of adult T-cell leukemia-lymphoma: a proposal from an international consensus meeting. J Clin Oncol. 2009;27(3):453-459.
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