Relapsed Adult T-cell Leukemia-lymphoma Research Articles

Durable remission with lenalidomide in a patient with early relapse of adult T-cell leukemia/lymphoma after cord blood transplantation

A 62-year-old woman with adult T-cell leukemia/lymphoma (ATL) received umbilical cord blood transplantation (CBT) in first complete remission. However, relapse of ATL was detected on day 74 post-transplantation, as evidenced by the rapid growth of lymphoma cells in peripheral blood and an increase in soluble interleukin-2 receptor (sIL2R) levels. Discontinuation of immunosuppressant therapy alone did not improve ATL findings, but treatment with lenalidomide caused lymphoma cells to disappear from the peripheral blood and sIL2R levels to return to normal. Pancytopenia was observed as a lenalidomide-associated adverse effect, but lymphocyte counts were not reduced. The patient was judged to be in complete remission based on results of Southern blot analysis and human T-cell leukemia virus 1 (HTLV-1)-infected cell analysis using flow cytometry (HAS-Flow). Flow cytometric analysis of peripheral blood and FISH analysis of X and Y chromosomes revealed that the therapeutic effect of lenalidomide was associated with an increase in the number of donor-derived peripheral natural killer cells. ATL relapse was not observed at 13 months into lenalidomide treatment. Our results suggest that lenalidomide is an effective option for the treatment of post-transplant relapsed ATL.

Mogamulizumab for post-transplant relapse of adult T-cell leukemia/lymphoma: a case study

Mogamulizumab (MOG), a humanized monoclonal anti-CCR4 antibody, exerts strong antibody-dependent cellular cytotoxic effects on CCR4-positive adult T-cell leukemia/lymphoma (ATLL) cells. As CCR4 is highly expressed on regulatory T cells as well as ATLL cells, pre-transplant MOG induces severe graft-versus-host disease (GvHD). However, limited data are available on post-transplant use of MOG for relapsed ATLL. Here we describe the case of a patient with ATLL who experienced post-transplant relapse with involvement of peripheral blood, skin, lungs, and lymph nodes. Neither tacrolimus dose reduction nor cytotoxic chemotherapy was effective, but a single dose of MOG (1 mg/kg) induced complete remission. After treatment with MOG, leukemic cells in the peripheral blood rapidly disappeared, and the skin, lymph node, and lung lesions gradually regressed. Most notably, the long-term remission was accompanied by recurrence of moderate acute GvHD (grade II, skin stage 2, gut stage 1, liver stage 0). Our findings indicate that MOG can augment allogeneic immune-mediated anti-tumor reactions through graft-versus-ATLL (GvATLL) even during post-transplant relapse involving the lymph nodes and lungs, along with inducing GvHD.

Proof of Merit in New Diet Therapy Against Adult T-Cell Leukemia/Lymphoma: Applying Specific Amino Acid Dependency of Leukemia/Lymphoma Cells

Introduction:Adult T-cell leukemia/lymphoma (ATL) is highly aggressive malignancy caused by human T-cell leukemia virus type 1 (HTLV-1). Because ATL cells are very aggressive, cytotoxic combination chemotherapy is used as first-line therapy. However, ATL cells are often resistant to chemotherapy. The intensive chemotherapy induces severe myelosuppression, which requires frequent transfusions, and organ damages. Unfortunately, accumulation of these adverse events disables continuation of treatment in some patients. Recently antibody therapy which targets CC chemokine receptor 4 (CCR4) expressed on ATL cells has been approved for the treatment of relapsed ATL, but lymphoma-like massive ATL cells in lymph nodes or spleen are known to be resistant to antibody therapy. Therefore, we sought to develop a new strategy, and finally focused on amino acids as asparaginase is used for treatment of acute lymphoblastic leukemia.Methods:Amino acid dependency of HTLV-1-infected cells, including ATL cells, was examined in vitro using HTLV-1-infected cell-lines and ATL cells which were serially passaged after purification by flow cytometry from the sample of an acute-type ATL patient. These cells were cultured with stromal cells in the medium which lacked one of twenty amino acids for 2 weeks. Proliferation of ATL cells and influence on stromal cells was examined, and we picked up amino acids which were crucial only for ATL cells. We next prepared diets which lacked specific amino acids based on in-vitro screening, and examined the effect in vivo using xeno-transplantation models. In a lymphoma model, massed ATL cells were transplanted intraperitoneally into adult NOG mice, which were fed complete diets. Diets were unchanged or changed to restricted ones after 6 weeks, and maximum tumor size was compared after 10 weeks. In a leukemia model, primary ATL cells, which were sorted from peripheral blood of an acute-type ATL patient, were transplanted intravenously into neonatal NOG mice within 24 hours from the birth. Recipient mice were brought up by the mother fed complete diets. After 4 weeks, recipient mice were weaned from breast, and fed complete diets or restricted ones. Peripheral blood was followed over time by flow cytometry, and infiltration of ATL cells into various organs was analyzed after 8 weeks.Results:In-vitro studies revealed that HTLV-1-infected cells have dependency on specific amino acids in common, and it was noteworthy that ATL cells could not proliferate in valine-deficient conditions while the influence on co-cultured stromal cells was limited. Therefore, we specially prepared valine-depleted diets, and confirmed that density of valine was very low in peripheral blood and bone marrow of mice fed valine-depleted diets. In-vivo lymphoma models showed that no masses were observed macroscopically in all of mice fed valine-depleted diets. In-vivo systemic leukemia models showed that valine-restricted diets preferentially reduced ATL cells but not hemoglobin or platelets in peripheral blood as shown in figure 1. Additionally, pathological examinations showed that valine-deficient diets strongly prevented ATL cells from proliferating and infiltrating into organs, such as spleen, liver, and skin. As far as we examined histologically, there were no significant organ damages.Discussion and Conclusions:Our study uncovered that adult T-cell leukemia/lymphoma cells failed to proliferate in valine-depleted conditions. The inhibition induced by dietary valine restriction was drastic, whereas ATL cells could proliferate to greater or lesser degrees in conditions lacking other amino acids, even if essential amino acids were depleted. Additionally, valine is indispensable for the proliferation and maintenance of hematopoietic stem cells (HSCs) as we previously reported. Therefore, valine-deficient diets could successfully reduce leukemic stem cells of ATL. Moreover, there were no severe complications such as anemia, thrombocytopenia, and organ damages which are often seen in chemotherapy recipients. Lymphoma-like massive ATL cells, which are often resistant to antibody therapies, were also vulnerable to valine-depleted conditions. The issues seen in currently available therapies against aggressive leukemia and lymphoma could be solved by this diet therapy itself or by adding this therapy to other treatments with reduced toxicity. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Allogeneic hematopoietic stem cell transplantation for adult T-cell leukemia-lymphoma.

Long survival is obtained in 30-40% of adult T-cell leukemia-lymphoma (ATL) patients with allogeneic hematopoietic stem cell transplantation (allo-HSCT) using HLA-matched related or unrelated donors. Myeloablative conditioning is generally used for patients 55 years of age and older, while reduced intensity conditioning is given to those between 50-70 years of age. Overall survival periods do not differ significantly between these two conditioning methods. Survival rates with cord blood transplantation are not inferior to those obtained with bone marrow transplantation or peripheral blood stem cell transplantation. Prognostic factors such as age, gender, performance status, disease status at transplantation and serum soluble interleukin-2 receptor are known to have an impact in ATL patients receiving allo-HSCT. Mild acute graft-versus host disease is associated with good overall survival. Cessation of immunosuppressants or donor lymphocyte infusion often induces another remission in relapsed ATL patients after allo-HSCT. This phenomenon is regarded as a graft-versus-ATL effect mediated by activated cytotoxic T-cells. Donor cell derived-ATL has, on rare occasion, been reported in patients receiving allo-HSCT from HTLV-1 carrier donors. Special attention should be paid to the use of mogamulizumab before allo-HSCT, since this agent kills normal regulatory T-cells as well as ATL cells.

P3-8-3 - Treatment outcome of GDP regimen for patients with refractory or relapsed adult T-cell leukemia-lymphoma

P3-8-3 - Treatment outcome of GDP regimen for patients with refractory or relapsed adult T-cell leukemia-lymphoma

A case of associated refractory acute graft-versus-host disease following umbilical cord blood transplantation in an adult T-cell leukemia/lymphoma patient pretreated with mogamulizumab

Adult T cell leukemia/lymphoma(ATLL)is a highly aggressive peripheral T-cell neoplasm associated with infection by a specific retrovirus, human T-cell lymphotropic virus type-I(HTLV-I). This hematological malignancy is resistant to conventional chemotherapy, and has a poor prognosis. Two previous multicenter trials for ATLL(Japan Clinical Oncology Group 9303 and 9801)evaluated the efficacy of dose-intensified multi-agent chemotherapy with vincristine, cyclophosphamide, doxorubicin, and prednisolone(VCAP), doxorubicin, ranimustine, and prednisolone(AMP), and vindesine, etoposide, carboplatin, and prednisolone(VECP)with granulocyte-colony stimulating factor(G-CSF)and intrathecal prophylaxis. However, these trials showed a median survival of only 13 months, not yielding satisfactory outcomes. Thus, a novel therapeutic modality is needed. A defucosylated humanized monoclonal antibody targeting CC chemokine receptor 4(CCR4), designated mogamulizumab, recently became available for this purpose. CCR4 is a chemokine receptor expressed on helper T cells, regulatory T cells(Tregs), and certain types of T-cell neoplasms, such as ATLL. With an increased binding affinity to the Fc-gamma receptor on effector cells, this drug markedly enhances antibody-dependent cell-mediated cytotoxicity(ADCC)against ATLL cells expressing CCR4. In a phase II clinical trial for relapsed ATLL, objective responses were noted in 13 of 26 evaluable patients, including eight complete responses. Although mogamulizumab is a promising therapeutic alternative for patients with relapsed/refractory ATLL, there is some apprehension regarding treating patients with mogamulizumab before allogeneic hematopoietic stem cell transplantation(allo-HSCT). The fear is that it might affect regulatory T cell(Treg)reconstitution because these cells also express CCR4. Fewer circulating Tregs cause severe graft-versus-host disease(GVHD)after allo-HSCT because these cells have an Case Report

Clinical Features and Treatment Outcomes of 81 Patients with Aggressive Type Adult T-cell Leukemia-lymphoma at a Single Institution over a 7-year Period (2006-2012).

Despite the remarkable advances in chemotherapy and allogeneic hematopoietic stem cell transplantation (HSCT), adult T-cell leukemia-lymphoma (ATL) is still associated with a high mortality rate. It is therefore essential to elucidate the current features of ATL. We retrospectively analyzed 81 patients with aggressive type ATL at our institution over a 7-year period based on Shimoyama's diagnostic criteria. Eighty-one patients with a median age of 67.5 years were classified as having acute (n=47), lymphoma (n=32), or chronic type (n=2) ATL. They were initially treated by either palliative therapy (n=25) or systemic chemotherapy [n=56; cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) therapy (n=25)/vincristine, cyclophosphamide, doxorubicin, and prednisone (VCAP)-doxorubicin, ranimustine, and prednisone (AMP)-vindesine, etoposide, carboplatin, and prednisone (VECP) therapy (VCAP-AMP-VECP) or CHOP-VMMV therapy (n=31)], and showed median survival durations of 16 and 277 days, respectively. Subsequent to the initial treatment, HSCT (n=6) was performed for certain patients, thus revealing that two-thirds (n=4) relapsed, and one-third (n=2) survived for 131 days and 203 days, respectively. The relapsed ATL patients were treated with conventional salvage therapy (n=29) or anti-CC chemokine receptor 4 antibody (mogamulizumab) (n=3). The patients treated with mogamulizumab demonstrated complete response (2) and partical response (1) with short duration periods of 82 days, 83 days, and 192 days, respectively. Among the five long-term survivors (>5 years) who received chemotherapy, most showed a low and intermediate risk according to the ATL prognostic index. In our study, the overall survival of ATL remains poor due to the advanced age of the patients at diagnosis, a high proportion of patients receiving palliative therapy, and a small proportion of long-term survivors receiving chemotherapy and undergoing HSCT. This study illustrates the current clinical features, treatment strategies, and outcomes in clinical practice.

Mogamulizumab for the treatment of adult T-cell leukemia/lymphoma

Mogamulizumab for the treatment of adult T-cell leukemia/lymphoma Makoto Yoshimitsu, Naomichi Arima Division of Hematology and Immunology, Center for Chronic Viral Diseases, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan Abstract: Adult T-cell leukemia/lymphoma (ATLL) is a peripheral T-cell lymphoma caused by latent infection of human T-cell lymphotropic virus type 1. The outcome for ATLL is very poor, with a 3-year overall survival of approximately 24% with conventional chemotherapy; thus, there is an unmet need for developing new treatment options. Defucosylated humanized anti-CC chemokine receptor 4 (CCR4) antibody (KW-0761, mogamulizumab) has been clinically available for the treatment of relapsed or refractory ATLL in Japan since 2012, and a Phase II study of mogamulizumab for patients with relapsed CCR4+ ATLL demonstrated a 50% objective response, a 30.8% complete response, and an acceptable safety profile. Allogeneic hematopoietic stem cell transplantation has been used to treat patients with ATLL, and mogamulizumab in combination with allogeneic hematopoietic stem cell transplantation has been used successfully in a limited number of patients to treat refractory or relapsed ATLL. The efficacy of combining mogamulizumab with standard chemotherapy (mLSG15) for patients with ATLL has also been examined, and the results have shown higher rates of complete response with the combined therapy (52%) compared with for chemotherapy alone (33%). Mogamulizumab also has potential application in the treatment of human T-cell lymphotropic virus type 1-associated myelopathy/tropical paraparesis, Epstein–Barr virus-associated T-cell and natural killer-cell lymphoproliferative diseases, and peripheral and cutaneous T-cell lymphomas. Possible adverse events of mogamulizumab have been reported, such as cutaneous adverse reactions (including Stevens–Johnson syndrome), diffuse panbronchiolitis, reactivation of hepatitis B, and opportunistic infections. The treatment outcome of patients with ATLL might be improved by further optimizing the use of mogamulizumab and managing severe adverse events. In this review, we provide an overview of the current treatment options for patients with ATLL and a focused review on the use, application, and adverse events associated with mogamulizumab. Keywords: ATLL, anti-CCR4 antibody, defucosylated antibody, cutaneous adverse reaction

Successful treatment by donor lymphocyte infusion of adult T-cell leukemia/lymphoma relapse following allogeneic hematopoietic stem cell transplantation

Adult T-cell leukemia/lymphoma (ATLL) is a highly aggressive hematologic neoplasm that has an extremely poor prognosis; however, this has improved following recent progress in allogeneic hematopoietic stem cell transplantation (allo-HSCT). Several clinical studies have shown that discontinuation of immunosuppressant therapy induces durable remission in a significant number of post-transplant relapsed patients, suggesting that ATLL may be susceptible to a graft-versus-leukemia effect. Here, we report two cases with ATLL who received donor lymphocyte infusions (DLIs) for relapse after allo-HSCT; one patient achieved complete remission (CR) after a single DLI, and the other suffered repeated relapses and was treated with chemotherapy and radiotherapy combined with a total of five rounds of DLIs. Both patients presented with exacerbation of the graft-versus-host disease after the DLIs, and remained in CR for 9 and 8 years, respectively. These data support the use of DLIs as an effective therapy to induce durable CR in the treatment of relapsed ATLL. In this study, we review previous reports and discuss the role of DLIs in the treatment of post-transplant relapsed ATLL.

Antibody therapy for Adult T-cell leukemia–lymphoma

Adult T-cell leukemia-lymphoma (ATL) has a very poor prognosis. Since there currently are limited treatment options for ATL patients, several novel agents are being developed and tested clinically. Antibody therapy against ATL was initially started with interleukin-2 receptor α-subunit, CD25, as a target molecule in the late 1980s, and is currently ongoing. CC chemokine receptor 4 (CCR4) was postulated as a novel molecular target in ATL antibody therapy, and humanized anti-CCR4 mAb (KW-0761), whose Fc region was defucosylated to enhance antibody-dependent cellular cytotoxicity, was developed. A phase I study of KW-0761 in relapsed ATL and peripheral T-cell lymphoma was started in 2006, and a subsequent phase II study was completed in 2010. KW-0761 showed a clinically meaningful antitumor activity in patients with relapsed ATL, with an acceptable toxicity profile. The prognosis of ATL patients should be improved in the near future with clinical applications of novel treatment strategies, including those involving KW-0761 and other promising antibody therapies targeting CD25 or CD30.

Promising results of an anti-CCR4 antibody, KW-0761, for relapsed Adult T-Cell Leukemia-Lymphoma (ATL)

Background ATL is an aggressive T-cell malignancy caused by the virus HTLV-1 with a very poor outcome. ATL, and is characterized by its cell surface expression of CC chemokine receptor 4 (CCR4), to which KW-0761, a defucosylated, humanized antibody with enhanced antibodydependent cellular cytotoxicity (ADCC), binds. In a phase I study of KW-0761 in 13 patients (pts) with CCR4-positive relapsed ATL, encouraging efficacy of KW-0761 was observed (ORR of 31%; 2CRs and 2PRs, ref. 3). Here, we report the result of a pivotal phase II study of KW-0761 in pts with CCR4-positive relapsed ATL.

Multicenter Phase II Study of KW-0761, a Defucosylated Anti-CCR4 Antibody, In Relapsed Patients with Adult T-Cell Leukemia-Lymphoma (ATL)

AbstractAbstract 285 Background:KW-0761 is a defucosylated, humanized, monoclonal antibody with enhanced antibody-dependent cellular cytotoxicity (ADCC; Potelligent®) that binds to CC chemokine receptor 4 (CCR4). CCR4 is expressed on the surfaces of cells comprising several T-cell malignancies such as ATL, peripheral T-cell lymphoma (PTCL) and cutaneous T-cell lymphoma (CTCL). A phase I study of KW-0761 in patients with CCR4-positive ATL and PTCL demonstrated that 4 weekly intravenous infusions of KW-0761 were well tolerated up to 1.0 mg/kg and it showed encouraging clinical activity with an overall response rate (ORR) of 31.3% (4 of 13 ATL and 1 of 3 PTCL) in 16 patients (J Clin Oncol 2010;28:1591-8). Methods:A multicenter phase II study of KW-0761 has been conducted for relapsed patients with CCR4-positive ATL to evaluate its efficacy, pharmacokinetics (PK), safety and immunogenicity. Patients were planned to receive 8 weekly intravenous infusions of KW-0761 at 1.0 mg/kg. The primary endpoint was ORR. Objective responses were assessed after the 4th and 8th infusions of KW-0761 according to the response criteria for ATL (J Clin Oncol 2009;27:453-9) by each investigator and the independent efficacy assessment committee. The number of patients required was estimated to be 25, for 90% power to detect a lower limit of the 95% confidence interval (CI) exceeding the 5% threshold of ORR, based on the assumptions that the minimum required response ORR to a new drug for relapsed ATL is 5% and the expected ORR to KW-0761 is 30%. Results:Twenty-seven patients (12 males and 15 females) were enrolled and received KW-0761. The median age was 64 years (range: 49–83). The disease subtypes of ATL consisted of 14 acute-, 6 lymphoma-, and 7 chronic-types with unfavorable prognostic factors. Among the 27 patients enrolled, 14 patients (52%) completed the protocol treatment of 8 infusions. Eleven patients (41%) discontinued the protocol treatment because of progressive disease, and the remaining 2 discontinued because of skin rash or the concurrent colon tumor. The treatment-related grade (G) 2 or greater adverse events (AEs) were lymphopenia (96%), leukopenia (56%), skin rash (52%), neutropenia (33%), thrombocytopenia (26%), AST increase (26%), ALT increase (22%), hypoxemia (19%), anemia (15%), pruritus (15%), g-GTP increase (15%) and hypophosphatemia (15%). G2 or greater Infusion-related toxicities were observed in 22 of 27 patients (81%) including 1 G3, but immediately recovered after treatment with systemic steroids. Treatment-related severe AEs (SAEs) were observed in 5 patients, including a Stevens-Johnson syndrome (G3) and 4 skin rashes (each G3). All these AEs also improved by steroids. PK analysis demonstrated that Cmax and trough (C168h) after the 8th infusion was 38,853 ± 11,267 and 25,934 ± 10,193 ng/mL, respectively, and T1/2 after the 8th infusion were 457 ± 144 h. No anti-KW-0761 antibody has been detected. Among the 26 patients evaluable for efficacy, KW-0761 exhibited an ORR of 54% (14/26; 95% CI, 33 to 73) (acute: 6/14 patients, lymphoma: 3/6 patients, chronic: 5/6 patients) including 7 complete responses (CRs) (27%; 95% CI, 12 to 48) and 7 partial responses (PRs). These are remarkable results, considering that the ORR of relapsed or refractory patients with ATL to a single-agent chemotherapy has been reported to be low (7 to 39%). Response rates according to the affected disease lesion were 100% (13 patients, all CR), 71% (5 of 7 patients), and 38% (5 of 13 patients), respectively, for peripheral blood, skin, and lymph node disease. Conclusions:KW-0761 is a highly effective agent with acceptable toxicity profiles in relapsed patients with CCR4-positive ATL who have no standard therapies. A multicenter, randomized study for untreated ATL patients to compare mLSG15 (a dose-intensified multi-agent regimen, J Clin Oncol 2007;25:5458-64) + KW-0761 with mLSG15 alone has been initiated. Disclosures:Ogura:Kyowa Hakko Kirin Co Ltd: Consultancy. Akinaga:Kyowa Hakko Kirin Co Ltd: Employment.

Phase I Study of KW-0761, a Defucosylated Anti-CCR4 Antibody, in Relapsed Patients (Pts) with Adult T-Cell Leukemia-Lymphoma (ATL) or Peripheral T-Cell Lymphoma (PTCL): Updated Results.

Background: KW-0761 produced by POTELLIGENT® technology is a defucosylated humanized IgG1 monoclonal antibody against CC chemokine receptor 4 (CCR4). Fucose is demonstrated to be the most critical IgG1 oligosaccharide component for antibody-dependent cellular cytotoxicity (ADCC) activity and KW-0761 composed of defucosylated IgG1 exhibits an enhanced ADCC activity. Previous studies revealed that CCR4 was overexpressed on tumor cells from 88% of pts with ATL and 38% of pts with PTCL unspecified (PTCL-U), and its expression was associated with poor prognosis. CCR4 was also expressed in cutaneous T-cell lymphoma (CTCL) such as mycosis fungoides (MF) and Sezary syndrome, especially its large cell transformant. These results suggest that CCR4 could be a realistic therapeutic target for ATL, CTCL and PTCL-U.Methods: A multicenter phase I study of KW-0761 has been conducted for relapsed pts with CCR4-positive ATL or PTCL to evaluate its safety, pharmacokinetics (PK), immunogenicity and efficacy. Pts were planned to receive 4 weekly intravenous infusions of KW-0761 at 0.01, 0.1, 0.5, and 1.0 mg/kg. A dose-limiting toxicity (DLT) was defined as any of the following adverse events:≥ grade (G) 4 hematologic toxicities except for lymphopenia,≥ G4 acute infusion reaction/cytokine release syndrome or tumor lysis syndrome, or≥ G3 other non-hematologic toxicities. Plasma KW-0761 levels were assessed in all pts enrolled. Response was assessed by standard response criteria for NHL by each investigator.Results: As of August 18, 2008, 13 pts including 6 males and 7 females (11 ATL, 1 PTCL-U, 1 MF) were treated with KW-0761 at 0.01 (N=3), 0.1 (N=4), 0.5 (N=3) and 1.0 mg/kg (N=3). Median age was 62 years (range 46 – 69). KW-0761 was well tolerated without any DLT. ≥ G2 toxicities included: hematologic: lymphopenia (G4: N=2, G3: N=6, G2: N=3), neutropenia (G3: N=2, G2: N=3), eosinophilia and thrombocytopenia (G2: N=1, each); and non-hematologic: herpes zoster (3 months after the 4th dosing, G3: N=1), acute infusion reaction/cytokine release syndrome (G3: N=1, G2: N=4), constipation, rash, prolonged QTc, ALT increase, CRP increase, and pain of lymph node (G2: N=1, each). One pt enrolled at 0.1 mg/kg was withdrawn due to early disease progression. PK analysis showed that Cmax at 0.01 and 1.0 mg/kg after the 4th dosing were 324 ± 57 and 43469 ± 3819 ng/mL, respectively, and C168h at 0.01 and 1.0 mg/kg after the 4th dosing were 152 ± 12 and 21900 ± 3880 ng/mL, respectively. T1/2 at 0.01 and 1.0 mg/kg after the 4th dosing were 244 ± 117 and 554 ± 125 h, respectively. No anti-KW-0761 antibody has been detected. Complete response (CR) was observed in one ATL pt (0.1 mg/kg) with the disappearance of abnormal blood cells and skin disease, and in one PTCL-U pt (1.0 mg/kg) with the disappearance of abnormal blood cells, skin disease and enlarged lymph node. Overall, investigator-assessed responses for 13 enrolled pts were 31% including 2 CRs, 2 PRs (ATL at 0.01, and 0.1 mg/kg) and 4 SDs (ATL at 0.01, 0.1 and 1.0 mg/kg).Conclusions: KW-0761 was tolerable across a wide range (0.01 – 1.0 mg/kg) and had clinical activity in relapsed CCR4-positive ATL or PTCL. KW-0761 is a promising new antibody therapy for ATL and PTCL. Patient accrual is ongoing and the updated results will be presented.