Many advances have emerged in the field of peripheral T-cell lymphoma. Most of the trials have focused on investigating the role of new drugs in relapsed tumors or synergistic effects in combination with other drugs. At the same time, a number of novel drugs have entered the therapeutic foreground. 2009 saw pralatrexate become the first drug approved for the treatment of peripheral T-cell lymphoma. Last summer, two other drugs were approved, romidepsin and brentuximab vedotin. brentuximab vedotin has been used to treat mesenchymal large cell lymphoma and Hodgkin’s lymphoma. The PROPEL trial focused on the treatment of 109 relapsed or refractory peripheral T-cell lymphomas with pralatrexate. The overall effectiveness was 29% with a median duration of 10.1 months. 131 patients with peripheral T-cell lymphoma were included in the Romidepsin trial. Pralatrexate and Romidepsin are both effective as third- or fourth-line treatment options. These drugs may be more effective if used in the early stages of treatment. Brentuximab vedotin is highly effective in CD30-positive relapsed Hodgkin’s lymphoma or mesenchymal large cell lymphoma. This drug primarily targets the CD30 molecule, a CD30 antibody that attaches to the surface of tumor cells and is endocytosed into the cells, allowing the chemotherapy drug to enter the nucleus. Most mesenchymal large cell lymphomas express CD30 molecules. In the phase II clinical trial, which included 58 patients, the efficacy rate was 86% and the complete remission rate was 53%. This result is very significant. Although the proportion of mesenchymal large cell lymphoma in T-cell lymphoma is low, at about 15-20%, the efficiency of the drug is high. Preliminary data on bendamustine for relapsed or refractory peripheral T-cell lymphoma were also available this summer. In 38 patients, the effectiveness rate was 47%, but the median duration of effectiveness was very short, at 157 days. The data suggest that bendamustine remains effective in these patients. The approach to studying Pralatrexate was slightly different. Although the evidence that CHOP regimens result in sustained remission remains inconclusive, most patients achieve partial or complete remission with CHOP regimens. An international trial is currently investigating whether these patients in remission can be maintained with Pralatrexate. Patients are randomized in a 2:1 ratio to receive Pralatrexate maintenance therapy or observation. This is open at the time of the trial. In the Phase I//II trial of Pralatrexate for cutaneous T-cell lymphoma, patients were 45% effective when administered at a dose of 15 mg/m2, which is less than half the standard dose for aggressive lymphoma. A phase I clinical trial is currently investigating the combination of pralatrexate and bexarotene for the treatment of cutaneous T-cell lymphoma, which is primarily used for the treatment of mycosis fungoides. Due to the increasing selectivity available, the greater the benefit for relapsed patients. Although no single drug is suitable for all individuals, for a given individual it means more options. Most drugs are currently administered continuously, so if a drug is effective, the expiration date is maximized. In CD30-positive mesenchymal large-cell lymphoma, Brentuximab vedotin has a very high efficiency. Recent trials are currently investigating the effect of Brentuximab vedotin in other CD30-positive tumors. The goal is to find an effective minimum CD30 expression rate. These trials help us to deduce which patients are indicated for this drug. For other drugs, such as Pralatrexate and Romidepsin, we still lack the appropriate markers to predict which patients are effective. trials of Pralatrexate suggest that patients with AITL may not be effective. The early NCI on Romidepsin was less effective, but the bulk of the trials showed similar rates between subtypes. The low number of patients with each subtype in the current clinical trials makes it difficult to determine which subtype has a better or worse prognosis. Other drugs of interest include the antibody to CCR4, KW-0761, which is expressed in many T-cell and T-cell lymphomas. in a Japanese trial of KW-0761 for the treatment of HTLV-1-associated lymphoma, the efficacy rate was 50% in 26 patients. The patients enrolled were CCR4 positive. Every effort is being made to enroll more patients to confirm the efficacy in HTLV-1 patients. In patients with nasal NK/T-cell lymphoma, L-asparaginase may be effective. Nasal NK/T-cell lymphoma occurs predominantly in Asia and most patients are EBV-positive. A trial is investigating the efficiency of L-asparaginase in this subset of lymphomas. A novel treatment regimen (SMILE) is currently being created in Japan: steroids, methotrexate, isocyclophosphamide, L-asparaginase, and etoposide. This regimen has a very high efficiency in nasal NK/T-cell lymphoma. We are also applying this regimen recently and confirmed this. Therefore, SMILE is a very effective regimen for this disease. In particular, the identification of effective drugs helps to improve the prognosis of patients with nasal NK/T-cell lymphoma. A US study included Pralatrexate in the treatment regimen, which was combined with a CHOP regimen. The main side effect of Pralatrexate is mucositis, especially oral ulcers. Patients taking Pralatrexate have suffered from mouth sores to varying degrees. Early trials have shown that folic acid and vitamin B12 are effective in relieving particularly severe mucositis. When the trial dose of the drug is 30 mg/m2, some patients will have grade III/IV mucositis. The best intervention option is to maintain this dose for a week, with most patients resolving within a week. Other options include calcium folinic acid, ice, and mouth rinsing, but no studies have shown these to be effective in reducing the incidence of mucositis. In relatively mild disease, Pralatrexate is generally started at a small dose, e.g., 20 mg/m2, and the dose is gradually increased if there are no side effects. This regimen is based in part on a study of cutaneous T-cell lymphoma, in which the dose of Pralatrexate was reduced from 30 mg/m2 to 10 mg/m2. when the dose used was 15 mg/m2, there was still a high rate of efficacy. When the dose was lower than 15 mg/m2, the efficiency rate was significantly lower. At the time of this trial, the incidence of mucositis was lower than in the PROPEL trial. The most common hematologic side effect of Pralatrexate was thrombocytopenia, which resolved with one week of drug discontinuation. Romidepsin is better tolerated, mainly for prolongation of the QT interval. In recent clinical trials in cutaneous T-cell lymphoma and peripheral T-cell lymphoma total, little to no QT prolongation of degree III or IV was seen. The higher doses applied in the previous trials may have overestimated the QT interval prolongation. In addition, investigators are gradually learning that most of the currently applied drugs cause prolongation of the QT interval. In recent clinical trials with Romidepsin, the incidence of QT interval prolongation was low, and the primary hematologic toxicity of Romidepsin remains thrombocytopenia. Similar to Pralatrexate, platelets will return to normal levels after 1 week of discontinuation of Romidepsin. In the Pro-led phase II trial, Brentuximab vedotin had a 21% grade III/IV neutropenia, 14% thrombocytopenia, and 10% peripheral sensory neurotoxicity. These side effects were manageable. This is an exciting time, but this excitement must be carefully controlled. Because T-cell lymphoma is not well controlled with CHOP regimens, there is a strong desire to incorporate these agents into the treatment regimen. The best way to do this is, of course, clinical trials. In the laboratory study phase, the combination of Pralatrexate and Gemcitabine was excitingly promising, but phase I trials confirmed that the combination had very serious toxic side effects and no synergistic effect was seen. When patients are not well treated, we try to combine drugs to improve efficiency. Nevertheless, drugs should be combined in the context of a well-designed clinical trial. Therefore, we should try to enroll more cases to derive more meaningful data.