238 primary ATL cells by ADCC activity in vitro (10 μg/mL). After the 4th administration of mogamulizumab at a dose of 1.0 mg/kg, its plasma half-life was approximately 18 days, which is comparable to the half-life (14 to 21 days) of endogenous human IgG. Lastly, although MTD was not reached, a tendency toward an increased incidence of grade 3 or higher toxicity was observed at 1.0 mg/kg. Therefore, it was concluded that a dose of 1.0 mg/kg should be recommen- ded for a subsequent phase II trial of this novel agent [44]. A subsequent phase II study of mogamulizumab (0761– 002 Study: ClinicalTrials.gov Identifier NCT 00920790) was conducted in patients with CCR4-positive relapsed ATL [45 ]. The primary endpoint was the best ORR, and the secondary endpoints included the best response of each disease site such as peripheral blood ATL cells, skin and nodal/extranodal lesions as well as PFS and OS. It was planned for 25 patients to be enrolled for efficacy analysis, assuming the expected ORR of 30 % with a 5 % threshold response rate. Mogamulizumab was intravenously adminis- tered once a week for 8 weeks at a dose of 1.0 mg/kg. In this study, 28 patients in total were enrolled. Of these, 27 patients who received mogamulizumab were included in the safety analysis, and 26 patients, excluding 1 patient who was judged ineligible for enrollment after starting mogamulizumab administration, were evaluated in the effi- cacy analysis. Of the 27 patients who received mogamuli- zumab, 14 had acute type, 6 lymphoma type, and 7 chronic type with unfavorable prognostic factors. The best ORR was 50 % (13/26) including 8 CR. With the lower limit of the 95 % confidence interval (30 % to 70 %) exceeding the threshold response rate of 5 %, the clinical efficacy of mogamulizumab was confirmed. Responses according to disease sites were 100 % (of 13 patients, all CR) for periph- eral blood, 63 % (of 8 patients, 3 CR and 2 PR) for skin, and 25 % (of 12 patients, 3 CR/CRu) for nodal and extranodal lesions. Median PFS and OS were 5.2 and 13.7 months, respectively. The best ORR was also calculated for each disease subtype, giving 43 % in patients with acute type (of 14 patients, 5 CR and 1 PR), 33 % in patients with lymphoma type (of 6 patients, 1 CR and 1 PR), and 83 % in patients with unfavorable chronic type (of 6 patients, 2 CR and 3 PR). Thus, it was demonstrated that mogamuli- zumab induced favorable responses in patients with any disease subtype of ATL. In addition, for each age group, the best ORR was 39 % (of 13 patients, 3 CR and 2 PR) in patients younger than 65 years, and 62 % (of 13 patients, 5 CR and 3 PR) in patients 65 years or older. The most common adverse events observed during the study were lymphopenia (96 %), neutropenia (52 %), and thrombocyto- penia (52 %) as hematologic toxicity, and acute infusion reaction (89 %) and skin eruption (63 %) as non- hematologic toxicity. There was no death related to mogamu- lizumab in either the phase I or phase II study. Of 8 serious Curr Hematol Malig Rep (2012) 7:235–240 adverse events with a relationship to mogamulizumab in the phase I and II studies, 5 events including 4 cases of skin eruption and 1 case of Stevens-Johnson syndrome occurred during the phase II study. However, these reactions were manageable with supportive measures including corticoste- roid or other drugs in all patients. Considering the seriousness of the disease, even skin eruption might be considered accept- able for the treatment of ATL by treating physicians, while close and appropriate follow-up of the event is necessary. Elucidation of the mechanism of skin eruption and preventive measures against it are awaited. In the U.S., a phase I/II study (ClinicalTrials.gov Identi- fier: NCT00888927) in patients with relapsed or refractory PTCL including CTCL has been conducted [46]. Mogamu- lizumab was well tolerated at doses of 0.1–1.0 mg/kg in 42 patients including 1 with PTCL-NOS. MTD was not reached and thus 1.0 mg/kg was chosen for subsequent studies. A promising ORR of 42 % (of 38 evaluable patients with CTCL, 3 CR and 13 PR) was achieved, although expression of CCR4 on lymphoma cells was not mandatory for patient enrolment in this particular phase I/II study. Regarding subtypes of CTCL, ORR in Sezary syndrome (SS) patients was 50 % and in MF patients was 36 %. Eighty-seven percent of SS patients had a response in pe- ripheral blood, with 50 % CR. Further study of mogamuli- zumab is warranted in patients with nodal PTCL as well as CTCL. Conclusions It is evident that there are limitations to improvement of the treatment outcome of PTCL, especially ATL, with the cur- rently available chemotherapeutic agents alone. Mogamuli- zumab has a less severe toxicity profile and induces a high response rate in patients with ATL, even in elderly patients. Fig. 1 Ongoing clinical studies of mogamulizumab/KW-0761 for peripheral T-cell lymphomas in Japan