A5055192416- Lymphoma Diagnosis and Treatment
- Chronic Lymphocytic Leukemia Research
- Viral-associated cancers and disorders
- CNS Lymphoma Diagnosis and Treatment
- Immune Cell Function and Interaction
- Acute Myeloid Leukemia Research
- CAR-T cell therapy research
- Multiple Myeloma Research and Treatments
- Chronic Myeloid Leukemia Treatments
- Hematopoietic Stem Cell Transplantation
- T-cell and Retrovirus Studies
- Acute Lymphoblastic Leukemia research
- Cutaneous lymphoproliferative disorders research
- Folate and B Vitamins Research
- RNA modifications and cancer
- Porphyrin Metabolism and Disorders
- Epigenetics and DNA Methylation
- Hemoglobinopathies and Related Disorders
- Immunodeficiency and Autoimmune Disorders
- Protein Degradation and Inhibitors
- Erythrocyte Function and Pathophysiology
- Polyomavirus and related diseases
- Lung Cancer Treatments and Mutations
- Mesenchymal stem cell research
- Virus-based gene therapy research
Tohoku University Hospital
2016-2025
Tohoku University
2016-2025
Saitama Medical University
2020
Center for Rheumatology
2016
In-Q-Tel
2014
National University Cancer Institute, Singapore
2014
National University of Singapore
2014
Aichi Cancer Center
2005-2007
Hiroshima University
2000-2003
Hiroshima University Hospital
2000
Abstract Background The safety, tolerability, efficacy, and pharmacokinetics of tirabrutinib, a second-generation, highly selective oral Bruton’s tyrosine kinase inhibitor, were evaluated for relapsed/refractory primary central nervous system lymphoma (PCNSL). Methods Patients with PCNSL, Karnofsky performance status ≥70, normal end-organ function received tirabrutinib 320 480 mg once daily (q.d.) in phase I to evaluate dose-limiting toxicity (DLT) within 28 days using 3 + dose escalation...
Tirabrutinib is a second-generation Bruton's tyrosine kinase inhibitor with greater selectivity than ibrutinib. Here, we conducted multicenter, phase II study of tirabrutinib in patients treatment-naïve (Cohort A) or relapsed/refractory B) Waldenström's macroglobulinemia (WM). Patients were treated 480 mg once daily. The primary endpoint was major response rate (MRR; ≥ partial response). Secondary endpoints included overall (ORR; minor response), time to (TTMR), progression-free survival...
Intravascular large B-cell lymphoma (IVLBCL) is a rare type of extranodal for which prognosis typically poor without timely diagnosis. To explore the safety and efficacy standard chemotherapy combined with central nervous system (CNS)-directed therapy, we conducted multicentre, single-arm, phase 2 trial in untreated IVLBCL patients CNS involvement at diagnosis (PRIMEUR-IVL). In primary analysis, PRIMEUR-IVL study demonstrated 2-year progression-free survival (PFS) 76% overall (OS) 92% low...
Systemic chronic active Epstein-Barr virus infection (sCAEBV) was defined as a T- or NK-cell neoplasm in the 2017 World Health Organization (WHO) classification. To clarify clinical features of sCAEBV under this classification and review effects chemotherapy, we performed nationwide survey Japan from 2016 through 2018 patients with newly diagnosed January 2003 March 2016. One hundred cases were evaluated. The aged 1 to 78 years (median, 21) included 53 males 47 females. Spontaneous...
The ONO-4059-02 phase 1/2 study showed favorable efficacy and acceptable safety profile of tirabrutinib, a second-generation Bruton's tyrosine kinase inhibitor, for relapsed/refractory primary central nervous system lymphoma (PCNSL). Here, we report the long-term after 3-year follow-up.
Hypoxia promotes stem cell maintenance and tumor progression, but it remains unclear how regulates long-term adaptation toward these processes. We reveal a striking downregulation of the hypoxia-inducible histone H3 lysine 9 (H3K9) demethylase JMJD1A as hallmark clinical human germ cell-derived tumors, such seminomas, yolk sac embryonal carcinomas. Jmjd1a was not essential for self-renewal played crucial role suppressor in opposition to hypoxia-regulated oncogenic H3K9 methyltransferase G9a....
Overexpression of programmed death-1 (PD-1) ligands contributes to an immunosuppressive microenvironment. Nivolumab is a PD-1-blocking antibody that inhibits the PD-1 pathway and showed good efficacy in several types malignancy. This phase II study examined safety nivolumab 17 Japanese patients with refractory/relapsed classical Hodgkin lymphoma previously treated brentuximab vedotin. Sixteen were included analyses analyses. The primary endpoint was centrally assessed objective response rate...
We evaluated the safety, efficacy, pharmacokinetics, pharmacodynamics and predictive biomarkers of tirabrutinib, a second‐generation, enhanced‐selectivity Bruton's tyrosine kinase inhibitor in Japanese patients with relapsed/refractory B‐cell non−Hodgkin lymphoma (B‐cell NHL ) chronic lymphocytic leukemia ( CLL ). This was an open‐label, multicenter, phase I study. Seventeen (male N = 8) median age 70 years were enrolled 4 dose cohorts (160 mg once daily [N 3], 320 480 4] 300 twice 7]); had...
E7777 is a recombinant cytotoxic fusion protein composed of the diphtheria toxin fragments A and B human interleukin-2. It shares an amino acid sequence with denileukin diftitox, but has improved purity increased percentage active monomer. We undertook multicenter, single-arm phase II study in patients relapsed or refractory peripheral T-cell lymphoma (PTCL) cutaneous (CTCL) to evaluate its efficacy, safety, pharmacokinetics, immunogenicity. total 37 were enrolled, which 17 19 had PTCL CTCL,...
Polatuzumab vedotin (pola) is a CD79b-targeted antibody-drug conjugate delivering potent antimitotic agent (monomethyl auristatin E) to B cells. This was an open-label, single-arm study of pola 1.8 mg/kg, bendamustine 90 mg/m2 , rituximab 375 (pola + BR) Q3W for up six cycles in patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) who received ≥1 prior line therapy and were ineligible autologous stem cell transplantation (ASCT) or experienced treatment failure ASCT....
The phase II study of tirabrutinib monotherapy at a daily dose 480 mg under fasting conditions for treatment-naïve and relapsed/refractory Waldenström's macroglobulinemia (ONO-4059-05 study) demonstrated promising efficacy tolerable safety profile. We conducted an unplanned analysis with median follow-up 24.8 months to update the results report patient-reported quality life. Of 27 enrolled patients, 22 patients continued receiving drug. major response assessed by independent review committee...
The prognosis of patients with primary mediastinal large B-cell lymphoma has improved over recent years. However, the optimal treatment strategy including role radiotherapy remains unknown. We retrospectively analyzed clinical outcomes 345 newly diagnosed in Japan. With a median follow up 48 months, overall survival at four years for treated R-CHOP (n=187), CHOP (n=44), DA-EPOCH-R (n=9), 2nd- or 3rd-generation regimens, and chemotherapy followed by autologous stem cell transplantation were...
Venetoclax (VEN) is used in patients with acute myeloid leukemia (AML) and primarily metabolized by CYP3A4, a major drug-metabolizing enzyme. Patients AML simultaneously administered VEN CYP3A4 inhibitors require more appropriate management of drug–drug interactions (DDIs). Here, we report two cases (54-year-old man 22-year-old woman) administrated inhibitors, such as posaconazole, cyclosporine, or danazol. In the first case, evaluated appropriateness timing for adjusting dosage subsequent...
Summary Zandelisib, a selective, potent PI3Kδ inhibitor, demonstrated favourable outcomes in patients with relapsed or refractory follicular lymphoma global phase II study. This study evaluated the efficacy and safety of zandelisib for marginal zone lymphoma. Sixty‐one received orally at 60 mg daily continuously first two 28‐day cycles, followed by intermittent dosing on Days 1–7 following each cycle until progressive disease unacceptable toxicity. Objective complete response rates were...
ABSTRACT CD5‐positive diffuse large B‐cell lymphoma (CD5+ DLBCL) is characterized by a poor prognosis and frequent central nervous system (CNS) relapse. Sandwich therapy comprising dose‐adjusted (DA)‐EPOCH‐R (etoposide, prednisolone, vincristine, cyclophosphamide, doxorubicin, rituximab) high‐dose methotrexate (HD‐MTX) (DA‐EPOCH‐R/HD‐MTX) showed excellent efficacy manageable safety in phase II study of patients diagnosed with stage II–IV CD5+ DLBCL. To validate the results that elucidate...