Clinical Impact of Mogamulizumab Against Aggressive ATL: A Single-Center Retrospective Analysis

Abstract

IntroductionAdult T cell leukemia/lymphoma (ATL) is a rare hematological malignancy which is associated with human T lymphotropic virus type I (HTLV-I). Aggressive ATL, such as acute, lymphoma and unfavorable chronic type, has a poor prognosis. Combination chemotherapies are transiently effective against ATL; however, ATL commonly becomes resistant to the conventional chemotherapies. The efficacy of a humanized anti-CC chemokine receptor 4 monoclonal antibody, mogamulizumab (MOG), against ATL has been reported in a phase 2 study. According to a clinical study, MOG seems to be ineffective in lymphoma type ATL compared with acute type ATL; however, outcome of aggressive ATL patients following MOG treatment according to patient's characteristics remains unknown. We present the results of a single center retrospective study of MOG efficacy in acute and lymphoma type ATL patients.Patients and MethodsWe retrospectively analyzed 59 aggressive ATL patients, including acute and lymphoma type, who were treated between August 2006 and August 2016 in Kansai Medical University Hospital. Data collected in this study included patient's characteristics such as age at diagnosis, sex, ATL subtype, ATL prognostic index (ATL-PI), BUN, and CRP. Overall survival (OS), MOG treatment, and adverse effects (AEs) were evaluated.ResultsOf the 59 ATL patients, 56 (male 30, female 26) were eligible for analysis. The median age was 65.5 years (range, 41-84 years). According to Shimoyama's criteria, 31 patients (55.4 %) presented with the acute type, and 25 (44.6 %) with the lymphoma type. Frequencies of the risk groups according to the ATL -PI were observed as 11 patients (19.6 %), 30 patients (53.6 %), and 15 patients (26.8 %), with low-, intermediate-, and high-risk, respectively. The median survival time (MST) and 1-year OS rate were 262.5 days (range, 1-2033 days) and 37.2 %, respectively. Thirty-three patients received treatments without MOG, and 2 patients received only supportive care. Twenty-one patients received MOG treatment. Of the 21 patients, 1 patient received MOG combined chemotherapy as an initial therapy. All patients treated with MOG as a salvage therapy had refractory or relapsed ATL when MOG treatment was initiated. Four patients received retreatment with MOG. Prior treatment regimen except MOG and allogeneic hematopoietic stem cell transplantation (aHSCT) was median 2 courses (range, 1-3 courses). MOG was used as monotherapy in 20 cases, and as combination therapy with other drugs in 7 cases. AEs were mostly manageable; however, toxic epidermal necrolysis was observed in 1 patient. The overall response rate was 55.6 % (CR 7, PR 8). OS was significantly higher in patients treated with MOG compared to patients treated without MOG (P < 0.05, MST: 7.8 months vs 17.4 months, 1-year OS rate: 21.1 % vs 64.6 %) (Fig 1). Specifically, in the intermediate- and high-risk groups, administration of MOG was associated with improved survival. Nine patients underwent aHSCT. Of the 9 patients, 3 were treated with MOG before aHSCT. These 3 patients did not develop grade II-IV acute GVHD and treatment related mortality.ConclusionMOG significantly improves aggressive ATL patients. Especially, patients who were diagnosed as having intermediate- and high-risk may be benefitted by MOG. Although AEs associated with MOG are mostly acceptable, MOG treatment may rarely cause severe AEs. [Display omitted] DisclosuresIto:Celgene Corporation: Honoraria; bristol myers squibb: Honoraria. Nomura:Fujimoto Pharmaceutical Co.: Research Funding; Jansen Pharmaceutical K.K.: Honoraria; Bristol-Meyer Squibb K.K.: Honoraria; Ono Pharmaceutical Co.,LTD.: Honoraria; Asahi Kasei Pharma K.K.: Honoraria; Takeda Pharmaceutical Co.,LTD.: Honoraria, Research Funding; Celgene K.K.: Honoraria, Research Funding.