236 regimens or relapse, with the exception of anaplastic lympho- ma kinase-positive anaplastic large cell lymphoma (ALK+ ALCL), which responds well to the cyclophosphamide, doxo- rubicin, vincristine, and prednisone (CHOP) regimen [9]. Among the various entities of PTCLs, adult T-cell leukemia- lymphoma (ATL) harbors the worst prognosis [10]. Here, we will discuss novel agents that have been developed for the treatment of ATL and other PTCLs, mainly focusing on moga- mulizumab/KW-0761, which is a humanized monoclonal an- tibody targeting CC chemokine receptor 4 (CCR4) that has been actively developed for clinical use in Japan and the United States. PTCL and Novel Agents PTCL-not otherwise specified (PTCL-NOS) and angioim- munoblastic T-cell lymphoma (AITL), which are the most common subtypes of PTCL (PTCL-NOS, 26 %; AITL, 19 %), show a poor prognosis with 5-year overall survival (OS) and failure-free survival (FFS) of about 30 % and 20 %, respectively [10]. Several new agents have recently been developed for the treatment of PTCL, mainly in patients with relapsed or refractory disease. Such agents have various mechanisms of action, including an immunomodulator (lenalidomide), a proteasome inhibitor (bortezomib), histone deacetylase inhibitors (vorinostat, romidepsin, panobinostat), antifolate (pralatrexate), and biologics including antibodies and antibody-toxin/drug conjugates (alemtuzumab, siplizu- mab, denileukin diftitox, and brentuximab vedotin) as well as nucleoside analogs such as fludarabine, gemcitabine, nelar- abine, and forodesine [11]. Of these agents, pralatrexate and romidepsin have been recently approved by the U.S. Food and Drug Administration (FDA) and are now being used in the U.S. for the treatment of relapsed or refractory PTCL. In 2011, brentuximab vedotin (formerly known as SGN-35) was also approved for the treatment of relapsed or refractory ALCL and Hodgkin lymphoma. ATL has the worst prognosis among PTCL, with 5-year OS and FFS of 14 % and 12 %, respectively [10]. ATL is a peripheral T-cell malignancy associated with human T-cell lymphotropic virus type I (HTLV-1), and is relatively frequent in southwestern Japan, West Africa, the Caribbean islands, and Brazil, which are HTLV-1 endemic areas [12]. It is esti- mated that there are about 1.2 million HTLV-1 carriers in Japan, of whom a few percent develop ATL [13], and approx- imately 700 to 1000 people die of this disease per year [14]. ATL is classified into four disease subtypes (acute, lymphoma, chronic, and smoldering), based on clinical features including leukemic changes, high lactate dehydrogenase, hypercalcemia and organ infiltration, and the median survival time varies according to the disease type: acute type, 6 months; lympho- ma type, 10 months; chronic type, 24 months; and smoldering Curr Hematol Malig Rep (2012) 7:235–240 type, 3 years or more [15]. It is recommended that treatment strategies should be selected according to the disease subtype [15]. In Japan, the acute type, lymphoma type, and chronic type with unfavorable prognostic factors have been regarded as aggressive ATL subtypes requiring immediate treatment, and intensive combination chemotherapy or allogeneic hema- topoietic stem-cell transplantation are generally recommended therapeutic options [16]. The Japan Clinical Oncology Group-Lymphoma Study Group (JCOG-LSG) has been investigating the efficacy of combination chemotherapy for aggressive lymphomas in- cluding ATL or for ATL alone since the early 1980s. At the start of the investigation, CHOP-like regimens were evalu- ated because ATL was considered to be a type of NHL, but the outcome was poor [17]. Then, the LSG15 regimen consisting of the drugs used in the CHOP regimen plus four other drugs (ranimustine, vindesine, etoposide, and carbo- platin) with the prophylactic use of granulocyte colony- stimulating factor (G-CSF) was evaluated. In a phase III trial, JCOG9801, this dose-intensified multiagent chemo- therapy regimen was shown to be more effective than CHOP-14 regimen, with a complete response rate of 40 %, 3-year OS of 24 %, and median survival time of 12.7 months [18, 19]. However, since the outcome of this dose-intensified regimen was still inferior to that in other PTCLs and B-cell lymphomas, further improvement is necessary. In Western countries, combination therapy with interferon-α and zidovu- dine has been widely used for all disease subtypes of ATL. A recently published meta-analysis suggested the effectiveness of this combination therapy for ATL, especially leukemic forms such as acute and chronic types [20]. Several new antibodies are currently under development for the treatment of T-cell lymphoma. They are based on the unique immunophenotypic features of ATL cells, which express mature T-cell antigens such as CD2, CD25 (inter- leukin [IL]-2 receptor), and CD52. Because of the unique intense expression of CD25 compared to that in other PTCL, monoclonal antibodies targeting the IL-2 receptor (anti-Tac), either radiolabeled or unlabelled (daclizumab), have been tested in patients with relapsed or refractory ATL. However, the clinical efficacy appears to be limited [21]. An anti-CD2 monoclonal antibody (siplizumab) [22], anti-CD52 antibody (alemtuzumab) [23, 24], and anti-transferrin receptor antibody (A24) [25] are also under development, but data are currently limited. Currently Available Therapeutic Agents for ATL Pentostatin and sobuzoxane are chemotherapeutic agents that were previously approved for the treatment of ATL in Japan. Pentostatin, a purine nucleoside analog that inhibits adenosine deaminase, has been reported to be effective for