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In Southeast Asia, particularly in Thailand, beta(0)-thalassemia/hemoglobin E (HbE) disease is a common hereditary hematological disease. It is associated with pathophysiological processes, such as the intramedullary destruction of immature erythroid cells and peripheral hemolysis of mature red blood cells. MicroRNA (miR) sequences, which are short non-coding RNA that regulate gene expression in a suppressive manner, serve a crucial role in human erythropoiesis. In the present study, the plasma levels of the erythroid-expressed miRNAs, miR-451 and miR-155, were analyzed in 23 patients with beta(0)-thalassemia/HbE and 16 control subjects. Reverse transcription-quantitative polymerase chain reaction analysis revealed significantly higher levels of plasma miR-451 and miR-155 in beta(0)-thalassemia/HbE patients when compared to the control subjects. Notably, among the beta(0)-thalassemia/HbE patients, a significant increase in miR-451 levels was detected in severe cases when compared with mild cases. The levels of plasma miR-451 correlated with reticulocyte and platelet counts. The results suggest that increased plasma miR-451 levels may be associated with the degree of hemolysis and accelerated erythropoiesis in beta(0)-thalassemia/HbE patients. In conclusion, miR-451 may represent a relevant biomarker for pathological erythropoiesis associated with beta(0)-thalassemia/HbE.

Purpose Microsatellite instability (MSI) has been a long-standing biomarker candidate for drug resistance in tumour cells. Despite numerous clinical studies, the data in the literature are not conclusive. The complexity of the MSI phenomenon in some malignancies may, at least partly, account for the discrepancy. In addition, methodological problems are also pointed out in the assay techniques. We previously established a unique fluorescent technique in which the major methodological problems in conventional assays are overcome. Application of this technique has revealed two distinct modes of microsatellite alterations, i.e. Type A and Type B. More importantly, we demonstrated that Type A MSI is the direct consequence of defective DNA mismatch repair (MMR) that causes cellular resistance against antineoplastic agents. Method We first applied this technique to adult T-cell leukaemia/lymphoma (ATLL). Results The MSI phenomenon was indeed observed in ATLLs (4/20, 20%). Intriguingly, the observed microsatellite alterations were invariably Type A, which implies that the tumours were MMR-defective. Indeed, clinical outcomes of patients with these MSI + tumours were significantly worse. Furthermore, multivariate analysis revealed that Type A MSI is an independent prognostic factor. Conclusion These observations strongly suggest the possibility of Type A MSI as a prognostic and potentially predictive biomarker in ATLL.

Purpose Few treatment options exist for adult T-cell leukemia/lymphoma (ATL), and the prognosis for this disease is poor. A phase I study of lenalidomide demonstrated preliminary antitumor activity in patients with relapsed ATL. The current phase II study evaluated the efficacy and safety of lenalidomide monotherapy in patients with relapsed or recurrent ATL. Patients and Methods Patients 20 years of age or older with acute, lymphoma, or unfavorable chronic subtype ATL, who had received one or more prior anti-ATL systemic chemotherapy and achieved stable disease or better on their last anti-ATL therapy with subsequent relapse or recurrence, were eligible. Patients received oral lenalidomide 25 mg/d continuously until disease progression or unacceptable toxicity. The primary end point was overall response rate; secondary end points included safety, tumor control rate (stable disease or better), time to response, duration of response, time to progression, progression-free survival, and overall survival. Results Objective responses were noted in 11 of 26 patients (overall response rate, 42%; 95% CI, 23% to 63%), including four complete responses and one unconfirmed complete response. The tumor control rate was 73%. The median time to response and duration of response were 1.9 months and not estimable, respectively, and the median time to progression was 3.8 months. The median progression-free survival and overall survival were 3.8 and 20.3 months, respectively. The most frequent grade ≥ 3 adverse events were neutropenia (65%), leukopenia (38%), lymphopenia (38%), and thrombocytopenia (23%), which were all manageable and reversible. Conclusion Lenalidomide demonstrated clinically meaningful antitumor activity and an acceptable toxicity profile in patients with relapsed or recurrent aggressive ATL, hinting at its potential to become a treatment option. Further investigations of lenalidomide in ATL and other mature T-cell neoplasms are warranted.

B-cell activating factor (BAFF) promotes the survival and adhesion of multiple myeloma (MM) cells. Tabalumab (LY2127399) is an anti-BAFF monoclonal antibody. This phase 1, multicenter, open-label, nonrandomized, dose-escalation study evaluated the safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of tabalumab in combination with bortezomib and dexamethasone in Japanese patients with relapsed or refractory MM (RRMM). Sixteen patients received intravenous i.v. tabalumab 100 mg (Cohort 1, n = 4) or i.v. tabalumab 300 mg (Cohort 2, n = 12) in combination with oral dexamethasone 20 mg/day and i.v. or s.c. bortezomib 1.3 mg/m(2) . All patients had treatment-emergent adverse events (TEAE) possibly related to study treatment; the most common TEAE were thrombocytopenia (81.3%), lymphopenia (43.8%) and increased alanine aminotransferase (43.8%). Two (20.0%) dose-limiting toxicities were observed, both in Cohort 2 (tabalumab 300 mg), which was below the predefined cutoff for tolerability (<33%). The pharmacokinetics of tabalumab were similar when bortezomib was coadministered i.v. versus s.c. The overall response rate was 56.3%, suggesting that the combined treatment was effective. In conclusion, combined treatment with these three agents was well tolerated in this population of Japanese patients with RRMM. The study was registered at www.clinicaltrials.gov (NCT01556438).

e19018 Background: The programmed death-1 (PD-1) immune checkpoint pathway regulates T-cell-mediated antitumor immune responses in various tumors. Nivolumab (Nivo) (Ono Pharmaceutical, Bristol-Myers Squibb), a human anti-human PD-1 monoclonal antibody, has shown its efficacy in various cancers. A phase I study of Nivo in patients (pts) with relapsed or refractory (R/R) hematologic malignancy (CA209039) revealed the tolerability and efficacy of Nivo monotherapy in R/R classical Hodgkin lymphoma (R/R cHL) pts. ONO-4538-15 is the first Japanese study on Nivo in R/R cHL pts given prior brentuximab vedotin (BV). Here we present the results of an interim analysis. Patients andMethods: BV is currently used for the treatment of R/R CD30-positive cHL based on its known efficacy. Nivo (3 mg/kg) was administered on Day 1 of a 14-day cycle to R/R cHL pts given prior BV. The primary endpoint, IRC-assessed overall response rate (ORR), was evaluated using the IWG criteria (Cheson, 2007). Adverse events (AEs) were assessed using NCI-CTCAE ver. 4.0. Results: A total of 17 R/R cHL pts were enrolled at 13 sites from Apr to Sep 2015 (men: 13, women: 4; median age: 63 years; PS 0: 8 1: 9; stage II: 4, III: 5, IV: 8) with a median follow-up period of 5.1 months. All pts had previously received BV. ORR was 75% in 16 efficacy-evaluable pts (12/16; 95% CI: 47.6–92.7), including CR in 4 pts and PR in 8 pts. In 8 BV-resistant pts, where PD or SD was assessed as best overall response (BOR) with BV, the BOR with Nivo included CR in 3 pts, PR in 4 pts, and NE in 1 pt. AEs were observed in all 17 pts. Two pts presented grade 3 or 4 AEs; lymphopenia in 1 pt, anemia, hyponatremia, and interstitialpneumonia in 1 pt. After data cut-off, 2 pts experienced serious AEs (fulminant type 1 diabetes mellitus in 1 pt; rash, hepatic function disorder, and pyrexia in 1 pt). All AEs were clinically manageable. Conclusions: The interim analysis of Japanese phase II study of Nivo suggested its high efficacy with acceptable safety profiles even in pts with BV-resistant R/R cHL. Clinical trial information: JapicCTI-142755 Clinical trial information: JapicCTI-142755.

Using the Double Chooz detector, designed to measure the neutrino mixing angle theta(13), the products of mu(-) capture on C-12, C-13, N-14, and O-16 have been measured. Over a period of 489.5 days, 2.3 x 10(6) stopping cosmic mu(-) have been collected, of which 1.8 x 10(5) captured on carbon, nitrogen, or oxygen nuclei in the inner detector scintillator or acrylic vessels. The resulting isotopes were tagged using prompt neutron emission (when applicable), the subsequent beta decays, and, in some cases, beta-delayed neutrons. The most precise measurement of the rate of C-12(mu(-), nu)B-12 to date is reported: 6.57(-0.21)(+0.11) x 10(3) s(-1), or (17.35(-0.59)(+0.35))% of nuclear captures. By tagging excited states emitting gamma s, the ground state transition rate to B-12 has been determined to be 5.68(-0.23)(+0.14) x 10(3) s(-1). The heretofore unobserved reactions C-12(mu(-), nu alpha)Li-8, C-13(mu(-), nu n alpha)Li-8, and C-13(mu(-), nu n)B-12 are measured. Further, a population of beta n decays following stopping muons is identified with 5.5 sigma significance. Statistics limit our ability to identify these decays definitively. Assuming negligible production of He-8, the reaction C-13(mu(-), nu alpha)Li-9 is found to be present at the 2.7 sigma level. Limits are set on a variety of other processes.

Peliosis hepatis (PH) is a condition involving benign tumors pathologically characterized by multiple blood-filled cavities, mostly affecting the liver and spleen. Androgenic-steroids are widely used in patients with bone marrow failure syndromes (e.g.: aplastic anemia) and these patients are at increased risk of developing PH. Although patients with PH are generally asymptomatic, PH can progress to liver failure and even fatal spontaneous intraabdominal hemorrhage. Therefore, early diagnosis is critical in order to prevent life-threatening complications of PH. We herein report a patient with PH which had been treated with danazol, who presented with liver dysfunction and multiple hepatic lesions on imaging studies at the time of diagnosis. Although the patient presented with disseminated intravascular coagulation (DIC), a bone marrow biopsy revealed no evidence of leukemic transformation. The patient was diagnosed as having danazol-induced PH, and these abnormalities spontaneously resolved after the discontinuation of danazol. PH is one of the most important complications of long-term administration of androgenic-steroids. Although the mechanisms remain unclear, the multiple blood-filled cavities characteristic of PH may be responsible for the development of DIC. Therefore, monitoring of coagulation markers might also be a key strategy for early diagnosis of PH.

Programmed cell death ligand 1 (PD-L1) is expressed on both select diffuse large B-cell lymphoma (DLBCL) tumor cells and on tumor-infiltrating nonmalignant cells. The programmed cell death 1 (PD-1)/PD-L1 pathway inhibits host antitumor responses; however, little is known about how this pathway functions in the tumor microenvironment. The aim of this study was to determine the clinicopathological impact of PD-L1(+) DLBCL. We performed PD-L1/PAX5 double immunostaining in 1253 DLBCL biopsy samples and established a new definition of PD-L1(+) DLBCL. We also defined the criteria for microenvironmental PD-L1(+) (mPD-L1(+)) DLBCL (ie, PD-L1(-) DLBCL in which PD-L1(+) nonmalignant cells are abundant in the tumor microenvironment). Of the 273 patients whose clinical information was available, quantitative analysis of PD-1(+) tumor-infiltrating lymphocytes (TILs) was performed. The prevalence rates of PD-L1(+) and mPD-L1(+) DLBCL were 11% and 15.3%, respectively. Both PD-L1(+) and mPD-L1(+) DLBCL were significantly associated with non-germinal center B-cell (GCB) type and Epstein-Barr virus positivity. The number of PD-1(+) TILs was significantly higher in GCB-type tumors and lower in mPD-L1(-) and PD-L1(+) DLBCL. Patients with PD-L1(+) DLBCL had inferior overall survival (OS) compared with that in patients with PD-L1(-) DLBCL (P = .0009). In contrast, there was no significant difference in OS between mPD-L1(+) and mPD-L1(-) DLBCL (P = .31). The expression of PD-L1 maintained prognostic value for OS in multivariate analysis (P = .0323). This is the first report describing the clinicopathological features and outcomes of PD-L1(+) DLBCL. Immunotherapy targeting the PD-1/PD-L1 pathway should be considered in this distinct DLBCL subgroup.

Administration of an anti-CC chemokine receptor 4 monoclonal antibody, mogamulizumab, before allogeneic bone marrow transplantation for adult T-cell leukemia/lymphoma

Abstract Background: Darinaparsin is a novel organic arsenic compound composed of dimethylated arsenic linked to glutathione, and has similar structure to one of the intermediates of the arsenic detoxification pathway. The mechanism of action includes induction of apoptosis in tumor cells, primarily through disruption of mitochondrial functions and increase in reactive oxygen species production. Two phase I studies of darinaparsin for injection were conducted in patients with relapsed or refractory (r/r) PTCL to evaluate its safety, efficacy and pharmacokinetics in Japan and Korea, respectively. Methods: Patients with histologically confirmed PTCL not otherwise specified (PTCL-NOS), angioimmunoblastic T-cell lymphoma (AITL), anaplastic lymphoma kinase (ALK) -positive anaplastic large cell lymphoma (ALCL) or ALK-negative ALCL who failed or were refractory to 1 or more prior systemic therapy were eligible. Darinaparsin was administered for 5 consecutive days at 200 mg/m2/day or 300 mg/m2/day every 4 weeks, or at 300 mg/m2/day every 3 weeks in the Japanese phase I study, and at 300 mg/m2/day every 4 weeks or every 3 weeks in the Korean phase I study. Darinaparsin was given intravenously over 1 hour, and the treatment was continued until disease progression or unacceptable toxicity. As one of the secondary endpoints, tumor response was explanatorily assessed by using the Revised Response Criteria for Malignant Lymphoma (Cheson BD et al, J Clin Oncol 2007) in patients who completed at least 2 cycles of treatment and who had evaluable data of FDG-PET and CT scan. Since use of an inorganic arsenic compound is limited by cardiotoxicity, the potential of darinaparsin to prolong QTcF and any possible relationship between darinaparsin plasma concentration and change in QTcF were assessed. Results: In these 2 studies, 17 Japanese patients and 6 Korean patients; a total of 23 patients, included 16 PTCL-NOS, 6 AITL and 1 ALK-negative ALCL; 14 males and 9 females, with a median age of 63 (range 22-83) years were enrolled. Dose-limiting toxicities occurred in 1 Japanese patient who received 300 mg/m2/day (grade [G] 3 hepatic dysfunction). Drug-related adverse events >= G3 were reported in 4 Japanese patients who received 300 mg/m2/day. Occurrence of diffuse large B-cell lymphoma was reported in 1 patient, anemia in 1, leukopenia in 1, neutropenia in 2, febrile neutropenia in 1, lymphopenia in 2, thrombocytopenia in 2, hepatic dysfunction in 1, nausea in 1 and activated partial thromboplastin time (APTT) prolonged in 1. No drug-related adverse event >= G3 was reported in Korean patients. No patient showed QTcF >500 msec or delta QTcF >60 msec throughout the study period. Concentration-dependent or treatment-duration-independent effect on the QTcF was not identified. There was no significant relationship between the plasma concentration of darinaparsin and a change in QTcF interval (r=0.003). Tumor response was assessed in 14 patients who completed at least 2 cycles of treatment, and objective response was observed in 4 patients (1 complete response and 3 partial responses). Five of 6 patients with stable disease showed tumor shrinkage to some extent. In Japanese and Korean patients who received 300 mg/m2/day, the mean (± SD) values of Cmax were 838 ± 181 and 708 ± 81 ng/mL, AUC0-24 were 12759 ± 3419 and 11282 ± 905 ng•h/mL, and t1/2 were 20 ± 6.3 and 20.6 ± 2.8 h, respectively. The systemic arsenic exposures were similar between Japanese and Korean patients. There was no apparent difference in the mean plasma concentration-time profiles between Japanese and Korean patients at the doses studied. Conclusion: The results from integrated data analysis of these 2 phase I studies revealed that darinaparsin was well tolerated at all doses and dosing schedules studied, and demonstrated its potential efficacy against r/r PTCL. Furthermore, it was suggested that 300 mg/m2/day for 5-consecutive days every 3 weeks would be the recommendable dosing schedule of darinaparsin for subsequent studies. Based on the promising results of these phase I studies, we are planning to conduct an Asian multicenter phase II study for r/r PTCL. Disclosures Kim: Kyowa-Kirin: Research Funding; Takeda: Research Funding; Novartis: Research Funding; Roche: Research Funding; Donga: Research Funding; Merck: Research Funding. Ogura:Eisai Co., Ltd.: Research Funding; Kyowa Hakko Kirin co., Ltd.: Research Funding; Zenyaku Kogyo Co., Ltd.: Research Funding; Chugai Pharmaceutical Co., Ltd.: Research Funding; Phizer Japan Inc.: Research Funding; Janssen Pharmaceutical K.K.: Research Funding; GlaxoSmithKline K.K.: Research Funding; MSD K.K.: Research Funding; AstraZeneca K.K.: Research Funding; Takeda Pharmaceutical Company Limited: Research Funding; Symbio Pharmaceuticals Limited: Research Funding; Solasia Phama K.K.: Research Funding; Mundipharma K.K.: Research Funding; Celgene K.K.: Research Funding; Sumitomo Dainippon Pharma Co., Ltd.: Research Funding. Uchida:Eisai Co., Ltd.: Research Funding. Ishizawa:Takeda: Speakers Bureau; Janssen: Research Funding; Takeda: Research Funding; Kyowa Kirin: Speakers Bureau; GSK: Research Funding; Kyowa Kirin: Research Funding; Celgin: Research Funding; Pfizer: Speakers Bureau; Celgin: Speakers Bureau. Tobinai:Gilead Sciences: Research Funding. Nagahama:Solasia Pharma K.K.: Employment. Sonehara:Solasia Pharma K.K.: Employment. Nagai:Servier: Research Funding; Mundipharma: Research Funding; Otsuka: Research Funding; Takeda: Research Funding; CMIC: Research Funding; Janssen: Research Funding; Gilead Sciences: Research Funding.

CD 20 positive myeloma with small lymphoplasmacytoid morphology is difficult to differentiate from mature B-cell lymphoma. A 71-year-old male was referred to our hospital because of osteolytic vertebral fractures and anemia. Urine was positive for Bence Jones protein, κ type. Bone marrow consisted of approximately 30% small lymphoplasmacytoid cells with scant cytoplasm, and these cells were positive for CD20, CD23 and CD138. FISH analysis revealed t(11;14)(CCND1/IGH). Myeloma with t(11;14) is closely associated with small lymphoplasmacytoid appearance and CD20 and CD23 expressions. The patient was diagnosed as having myeloma based on clinical and cytogenetic findings, and achieved VGPR (very good partial response) after treatment with lenalidomide.

Background: Based on its favorable effects on survival, azacitidine (AzaC) is now recognized as a first-line treatment option for higher-risk MDS. But the prognosis of patients who become resistant or intolerant to AzaC is still dismal (the median overall survival was 5.6 months, J Clin Onclol 2011;29:3322-7 Prebet T et. al.), and development of effective salvage therapies is eagerly awaited. A large number of tumor-associated antigens (TAAs) have been identified, and cancer vaccines utilizing their epitopes have shown some degree of clinical efficacies in various types of tumors. Wilms' Tumor 1 (WT1) is one of such promising TAAs with broad expressions in various tumors including MDS. WT4869 is a synthetic peptide vaccine derived from WT1 protein, and the phase 1/2 clinical study of WT4869 was conducted to evaluate the safety and efficacy in HLA-A*24:02+ MDS patients, with some exploratory biomarker analyses.

Abstract Introduction: Adult T-cell leukemia-lymphoma (ATL), a distinct subtype of peripheral T-cell lymphoma (PTCL), is caused by human T-lymphotropic virus type-I (HTLV-1). Although rare in the rest of the world, ATL accounts for 25% of PTCL cases diagnosed in Japan, where ATL cases are clustered in areas endemic for HTLV-1 infection. Studies of lenalidomide, an oral immunomodulatory agent that has antiproliferative and direct antineoplastic activity in cutaneous T-cell lymphoma and PTCL, have reported encouraging clinical activity. On the basis of the results from the ATLL-001 dose-finding study of lenalidomide (Uike et al. ASH 2012. Abstract 2737), this multicenter phase II study (ATLL-002) was designed to investigate the efficacy and safety of single-agent lenalidomide in Japanese patients with relapsed ATL. Methods: Patients with relapsed acute, lymphoma, or the unfavorable chronic subtype of ATL who were at least 20 years of age, had ECOG performance status 0-2, no prior allogeneic stem cell transplant, and who had failed at least 1 chemotherapy were included in the study. Patients refractory to their last prior therapy were excluded. Treatment consisted of oral lenalidomide 25 mg/day administered continuously until disease progression or unacceptable toxicity. The primary endpoint was overall response rate (ORR). The secondary endpoints were progression-free survival (PFS), duration of response (DOR), overall survival (OS), and safety. Response was assessed by central review using the criteria proposed by Tsukasaki et al in their international consensus report (J Clin Oncol. 2009;27:453-459.); safety was assessed per NCI CTCAE v4.0 criteria. The estimated number of patients required was 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 ORR to a new drug for relapsed or recurrent ATL is 5% and the expected ORR to lenalidomide is 25%. Results: Twenty-six patients were enrolled and received lenalidomide. The median age was 68.5 years (range, 53-81), with 15 (58%) acute, 7 (27%) lymphoma, and 4 (15%) unfavorable chronic type ATL patients. Patients had received a median of 2 (range, 1-4) prior chemotherapeutic or antibody agents for ATL, 11 (42%) of whom received prior mogamulizumab (anti-CCR4 antibody). At a median 3.8-month follow-up, lenalidomide met the primary endpoint by exhibiting an ORR of 42% (11/26; 95% CI, 23-63) (acute 33% [5/15], lymphoma 57% [4/7], unfavorable chronic 50% [2/4]), including 5 (19%) complete responses (CR)/CR unconfirmed (95% CI, 7 to 39; Table 1). Stable disease was 31%, and progressive disease was 27%. The median time to response was 1.9 months (95% CI, 1.8 to 3.7). Although the data were immature at the time of analysis, median DOR for all responders was not reached (NR) (95% CI, 0.5 months to NR), median PFS was 3.8 months (95% CI, 1.9 months to NR), and median OS was 20.3 months (95% CI, 9.1 months to NR). At the time of the data cut-off, 5 (19%) patients remained on lenalidomide treatment. The most common grade 3/4 adverse events (AEs), accounting for at least 10% of all cases, were neutropenia (65%), leukopenia (39%), lymphopenia (39%), thrombocytopenia (23%), anemia (19%), and hypokalemia (12%). Serious AEs were reported in 9 (35%) patients; only thrombocytopenia (2 patients [8%]) was observed in >1 patient. AEs led to dose reduction/interruption in 17 (65%) patients and study discontinuation in 6 (23%). Seven deaths occurred during the study, 6 due to disease progression and 1 due to pneumonia unrelated to lenalidomide treatment. Conclusions: In this multicenter, open-label, phase II study, lenalidomide monotherapy demonstrated a 42% ORR and acceptable tolerability profile. These results support the potential for lenalidomide monotherapy becoming a treatment option for patients with relapsed ATL. Table. Best response to lenalidomide in relapsed ATL ATL type All patients (N = 26) Acute (n = 15) Lymphoma (n = 7) Unfavorable chronic (n = 4) ORR, n (%) 11 (42) 5 (33) 4 (57) 2 (50) CR/CRu, n (%) 5 (19) 3 (20) 2 (29) 0 PR, n (%) 6 (23) 2 (13) 2 (29) 2 (50) SD, n (%) 8 (31) 6 (40) 0 2 (50) PD, n (%) 7 (27) 4 (27) 3 (43) 0 CR, complete response; CRu, CR unconfirmed; ORR, overall response rate; PD, progressive disease; PR, partial response; SD, stable disease. Disclosures Fujiwara: Celgene: Honoraria, Other: Research funding to my institution; travel, accommodations, expenses. Off Label Use: Lenalidomide to treat ATL. Ishida:Celgene K.K.: Other: Research Funding to my institution; Bayer Pharma AG: Other: Research Funding to my institution; Kyowa Hakko Kirin Co., LTD: Honoraria, Other: Research Funding to my institution. Moriuchi:Celgene: Other: Research Funding to my institution; travel, accommodations, expenses, Speakers Bureau. Jo:Celgene: Honoraria; Janssen: Honoraria; Takeda: Honoraria; Kyowa Kirin: Honoraria; Nippon Shinyaku: Honoraria. Ishizawa:Kyowa Kirin: Research Funding; Celgin: Research Funding; Janssen: Research Funding; Takeda: Research Funding; GSK: Research Funding; Takeda: Speakers Bureau; Kyowa Kirin: Speakers Bureau; Pfizer: Speakers Bureau; Celgin: Speakers Bureau. Tobinai:Gilead Sciences: Research Funding. Tsukasaki:Celgene: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Chugai: Consultancy, Research Funding; Novartis: Research Funding; Pfizer: Research Funding; Mundipharma: Research Funding; Kyowa Kirin Hakkou: Research Funding. Ogura:Mundipharma: Consultancy, Research Funding; MeijiSeika Pharma: Consultancy; Zenyaku: Research Funding; Eisai: Research Funding; Pfizer: Research Funding; Janssen: Research Funding; Celgene: Research Funding; Solaisia: Research Funding. Midorikawa:Celgene K.K.: Employment; Celgene Corporation: Equity Ownership. Ruiz:Celgene K.K.: Employment. Ohtsu:Celgene: Employment, Equity Ownership, Other: travel, accommodations, expenses.

Background: MEDI-551 is an affinity-optimized and afucosylated humanized IgG kappa anti-CD19 monoclonal antibody enhanced for antibody-dependent cellular cytotoxicity. In a previous multicenter, phase 1/2 trial conducted in the United States and Europe, an overall disease control (objective response + stable disease) rate of 73.5% was achieved with MEDI-551 in patients (N=83) with relapsed or refractory B-cell malignancies, and median progression-free survival was 9.4 months (95% CI, 3.9–18.6 months) (Forero-Torres A, et al. 2013, ASH meeting).