Page 18 - 2019_05-HaematologicaMondo-web

864
Editorials
400 mg and 800 mg daily in the front-line treatment of high-risk, Philadelphia-positive chronic myeloid leukemia: a European LeukemiaNet Study. Blood. 2009;113(19):4497-4504.
5. Cortes JE, Kantarjian HM, Goldberg SL, et al. High-dose imatinib in newly diagnosed chronic-phase chronic myeloid leukemia: high rates of rapid cytogenetic and molecular responses. J Clin Oncol. 2009;27(28):4754-4759.
6. Corstes JE, Baccarani M, Guilhot F, et al. Phase III, randomized, open-label study of daily imatinib mesylate 400 mg versus 800 mg in patients with newly diagnosed, previously untreated chronic myeloid leukemia in chronic phase using molecular end points: tyro- sine kinase inhibitor optimization and selectivity study. J Clin Oncol. 2010;28(3):424-430.
7. Breccia M, Alimena G. The significance of early, major and stable molecular responses in chronic myeloid leukemia in the imatinib era. Crit Rev Oncol Hematol. 2011;79(2):135-143.
8. Hehlmann R, Müller MC, Lauseker M, et al. Deep molecular response is reached by the majority of patients treated with ima- tinib, predicts survival, and is achieved more quickly by optimized high-dose imatinib: results from the randomized CML-study IV. J Clin Oncol. 2014;32(5):415-423.
9. Giobbie-Hurder A, Gelber RD, Regan MM. Challenges of guarantee- time bias. J Clin Oncol. 2013;31(23):2963-2969.
10. Dafni U. Landmark analysis at the 25-year landmark point. Circ Cardiovasc Qual Outcomes. 2011;4(3):363-371.
11. Freidlin B, Sun Z, Gray R, Korn EL. Phase III clinical trials that inte- grate treatment and biomarker evaluation. J Clin Oncol. 2013;31(25):3158-3161.
12. Russo D, Martinelli G, Malagola M, et al. Effects and outcome of a policy of intermittent imatinib treatment in elderly patients with chronic myeloid leukemia. Blood. 2013;121(26):5138-5144.
13. Saglio G, Jabbour E. First-line therapy for chronic phase CML: select- ing the optimal BCR-ABL1-targeted TKI. Leuk Lymphoma. 2018;59(7):1523-1538.
14. Clark RE, Polydoros F, Apperley JF wt al. De-escalation of tyrosine kinase inhibitor dose in patients with chronic myeloid leukaemia with stable major molecular response (DESTINY): an interim analy- sis of a non-randomised, phase 2 trial. Lancet Haematol. 2017;4(7):e310-e316.
15. Takimoto CH. Maximum tolerated dose: clinical endpoint for a bygone era? Target Oncol. 2009;4(2):143-147.
16. Soverini S, Colarossi S, Gnani A, et al. Contribution of ABL kinase domain mutations to imatinib resistance in different subsets of Philadelphia-positive patients: by the GIMEMA Working Party on Chronic Myeloid Leukemia. Clin Cancer Res. 2006;12(24):7374- 7379.
17. Eadie LN, Hughes TP, White DL. Patients with low OCT-1 activity and high ABCB1 fold rise have poor long-term outcomes in response to tyrosine kinase inhibitor therapy. Leukemia. 2018;32(10):2288- 2291.
18. Bransford S, Wang P, Yeung DT, et al. Integrative genomic analysis reveals cancer-associated mutations at diagnosis of CML in patients with high-risk disease. Blood. 2018;132(9):948-961.
19. Hsu WL, Preston DL, Soda M, et al. The incidence of leukemia, lym- phoma and multiple myeloma among atomic bomb survivors: 1950- 2001. Radiat Res. 2013;179(3):361-382.
20 Ballman KV. Biomarker: Predictive or Prognostic? J Clin Oncol. 2015;33(33):3968-3971.
21. Saussele S, Richter J, Guilhot J, et al. Discontinuation of tyrosine kinase inhibitor therapy in chronic myeloid leukaemia (EURO-SKI): a prespecified interim analysis of a prospective, multicentre, non- randomised, trial. Lancet Oncol. 2018;19(6):747-757.
22. Gagniuc PA. Markov chains: from theory to implementation and experimentation. 1st. ISBN 9781119387589 (ePub ebook)
23. Baccarani M, Deininger MW, Rosti G, et al. European LeukemiaNet recommendations for the management of chronic myeloid leukemia: 2013. Blood. 2013;122(6):872-884.
Mogamulizumab versus investigator choice in relapsed/refractory adult T-cell leukemia/ lymphoma: all four one or none for all?
William Johnson,1 Anjali Mishra,1 Adam Binder,1 Alejandro Gru2 and Pierluigi Porcu1
1Division of Hematologic Malignancies and Hematopoietic Stem Cell Transplantation, Department of Medical Oncology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA and 2Division of Hematopathology, Department of Pathology, University of Virginia, Charlottsville, VA, USA
E-mail: PIERLUIGI PORCU - pierluigi.porcu@jefferson.edu doi:10.3324/haematol.2018.214536
The human T-cell lymphotropic (or leukemia) virus type-1 (HTLV-1) was isolated by Poiesz et al. in 1980 from the T-cell line Hut-102, established from a patient thought to have cutaneous T-cell lymphoma.1 HTLV-1 causes adult T-cell leukemia/lymphoma (ATL), HTLV-1 associated myelopathy/tropical spastic paresis (HAM/TSP), and other inflammatory disorders.2 ATL is a clinically heterogeneous but often very aggressive mature T-cell neoplasm with dismal survival rates and limited therapeutic options, particularly in the relapsed/refracto- ry (R/R) setting.3 Most cohort studies and clinical trials in ATL come from Japan where the virus is highly endemic in certain regions. Here, investigators have led efforts to define diagnostic criteria, clinical subtypes, prognostic models, and the value of new therapies, including the anti-CCR4 antibody mogamulizumab (KW-0761), approved in Japan for both R/R and chemotherapy-naïve CCR4-positive ATL.4,5 Data on subtype frequency, natural history, and outcome in ATL from non-Japanese endemic regions and from non-endemic regions (North America, Europe) remain very limited, although recent studies have
begun to shed some light on this, showing that North American ATL patients present with more aggressive dis- ease and have a worse prognosis (median survival approx. 7 months) compared to Japanese patients.6,7 The availability of mogamulizumab for ATL in Japan provided the impetus to explore its activity in other ATL popula- tions. In this issue of Haematologica, an important study by Phillips et al.8 significantly advances our understand- ing of the global therapeutic impact of mogamulizumab in ATL, by reporting results of an international random- ized Phase II trial (KW-0761-009) assessing the safety and efficacy of mogamulizumab versus investigator choice of chemotherapy in patients with R/R ATL.
HTLV-1 belongs to a group of T-lymphotropic deltaretroviruses, which includes four types of Simian T- lymphotropic viruses (STLV). HTLV-1 is believed to have originated from interspecies transmission between STLV- 1-infected Old-World monkeys and humans. HTLV-1 is highly endemic in Southwestern Japan, the Caribbean, Northern Iran, and in Aboriginal populations in central Australia.9 HTLV-1 RNA is reverse-transcribed into a
haematologica | 2019; 104(5)