18 results on '"N, Fukuhara"'
Search Results
2. Japanese phase Ib study of the oral PI3K-δ and -γ inhibitor duvelisib in patients with relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma.
- Author
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Makita S, Ota S, Mishima Y, Usuki K, Ennishi D, Yanada M, Fukuhara N, Yamamoto R, Takamine A, Nohara G, and Izutsu K
- Subjects
- Humans, Phosphatidylinositol 3-Kinases, Japan, Recurrence, Proto-Oncogene Proteins c-bcl-2, Leukemia, Lymphocytic, Chronic, B-Cell drug therapy, Antineoplastic Agents adverse effects, Neutropenia, Anemia, Isoquinolines, Purines
- Abstract
This phase Ib, open-label, single-arm, multicenter study assessed the efficacy and safety of duvelisib, an oral dual inhibitor of phosphatidylinositol 3-kinase-δ and -γ, in Japanese patients with relapsed or refractory (r/r) chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). Duvelisib was administered orally at 25 mg twice a day (BID) until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) and all responses were assessed by an independent review committee. Nine CLL patients and 1 SLL patient were enrolled. ORR was 80% (95% confidence interval 44.4, 97.5) for all 10 patients. All 6 patients previously treated with a Bruton's tyrosine kinase (BTK) or BCL2 inhibitor achieved a partial response. The most common adverse events were neutropenia (50%), diarrhea (40%), anemia, hypokalemia, constipation and rash (30% each). The most common grade ≥ 3 adverse events were neutropenia (50%), anemia (30%) and thrombocytopenia (20%). Duvelisib 25 mg BID showed favorable efficacy and a manageable safety profile in selected Japanese patients with r/r CLL/SLL, including patients previously treated with BTK or BCL2 inhibitors (Clinical trial registration: jRCTs2080224791)., (© 2023. Japanese Society of Hematology.)
- Published
- 2024
- Full Text
- View/download PDF
3. Measurable residual disease in Japanese patients with relapsed or refractory chronic lymphocytic leukemia treated with venetoclax.
- Author
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Izutsu K, Yamamoto K, Kato K, Ishikawa T, Fukuhara N, Terui Y, Choi I, Okubo S, Ogawa N, Sakai M, Nishimura Y, Chyla B, Sun Y, and Maruyama D
- Subjects
- Humans, East Asian People, Rituximab therapeutic use, Bridged Bicyclo Compounds, Heterocyclic therapeutic use, Antineoplastic Combined Chemotherapy Protocols adverse effects, Leukemia, Lymphocytic, Chronic, B-Cell drug therapy, Antineoplastic Agents therapeutic use
- Published
- 2023
- Full Text
- View/download PDF
4. Long-term safety profile of tirabrutinib: final results of a Japanese Phase I study in patients with relapsed or refractory B-cell malignancies.
- Author
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Munakata W, Ando K, Yokoyama M, Fukuhara N, Yamamoto K, Fukuhara S, Ohmachi K, Mishima Y, Ichikawa S, Ogiya D, Aoi A, Hatsumichi M, and Tobinai K
- Subjects
- Humans, East Asian People, B-Lymphocytes pathology, Leukemia, Lymphocytic, Chronic, B-Cell drug therapy, Lymphoma, Non-Hodgkin drug therapy
- Abstract
Tirabrutinib is a Bruton's tyrosine kinase inhibitor for treating B-cell malignancies. We report the final results of a Phase I study of tirabrutinib in 17 Japanese patients with B-cell malignancies. Patients were administered tirabrutinib at a dose of 160 mg, 320 mg, or 480 mg once daily, or 300 mg twice daily (N = 3, 3, 4, and 7, respectively). Three patients continued tirabrutinib until study completion (November 30, 2020). Adverse events (AEs) occurred in all 17 patients, with Grade 3-4 AEs in 8 (47.1%), serious AEs in 7 (41.2%), drug-related AEs in 16 (94.1%), and Grade 3-4 drug-related AEs in 6 (35.3%). Drug-related AEs reported in 3 or more patients were rash, vomiting, neutropenia, arthralgia, and malaise. One additional serious AE (benign neoplasm of the lung, unrelated to tirabrutinib) occurred after the previous data cutoff (January 4, 2018). Tirabrutinib administration and response assessment were continued for over 4 years in 4 patients. The overall response rate was 76.5% (13/17 patients). The median (range) time to response and duration of response were 0.9 (0.9-5.9) months and 2.59 (0.08-5.45) years, respectively. These findings demonstrate the long-term safety and efficacy of tirabrutinib in Japanese patients with B-cell malignancies.Clinical trial registration: JapicCTI-142682 ( http://www.clinicaltrials.jp/ )., (© 2022. The Author(s).)
- Published
- 2023
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5. Efficacy and safety of tisagenlecleucel in adult Japanese patients with relapsed or refractory follicular lymphoma: results from the phase 2 ELARA trial.
- Author
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Fukuhara N, Kato K, Goto H, Takeshi T, Kawaguchi M, Tokushige K, Akashi K, Teshima T, Harigae H, Schuster SJ, Thieblemont C, Dreyling M, and Fowler N
- Subjects
- Humans, Adult, East Asian People, Receptors, Antigen, T-Cell therapeutic use, Progression-Free Survival, Immunotherapy, Adoptive adverse effects, Lymphoma, Follicular pathology
- Abstract
Background: Tisagenlecleucel yielded a high durable response rate in patients with relapsed/refractory (r/r) follicular lymphoma (FL) in the global phase 2 ELARA trial. Here, we report the efficacy, safety, and cellular kinetics of tisagenlecleucel in a subgroup of Japanese patients with r/r FL from ELARA., Methods: ELARA (NCT03568461) is a global single-arm trial of tisagenlecleucel in patients with r/r FL who received ≥ 2 prior lines of therapy. The primary endpoint was the complete response rate (CRR), and the secondary endpoints were the overall response rate, duration of response, progression-free survival, overall survival, safety, and cellular kinetics., Results: As of March 29, 2021, nine Japanese patients were enrolled and received tisagenlecleucel with a median follow-up of 13.6 months (range, 10.5‒19.3). Per independent review committee, CRR was 100% (95% CI 63.1‒100). Within 8 weeks of infusion, cytokine release syndrome (CRS) of any grade was reported in 6 patients (66.7%); however, no grade ≥ 3 CRS or any grade serious neurological events or treatment-related deaths were observed., Conclusion: Tisagenlecleucel showed high efficacy and manageable safety in adult Japanese patients with r/r FL. Moreover, the clinical outcomes were similar to the global population, which supports the potential of tisagenlecleucel in Japanese patients with r/r FL., (© 2022. The Author(s).)
- Published
- 2023
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6. Safety and antitumor activity of copanlisib in Japanese patients with relapsed/refractory indolent non-Hodgkin lymphoma: a phase Ib/II study.
- Author
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Fukuhara N, Maruyama D, Hatake K, Nagai H, Makita S, Kamezaki K, Uchida T, Kusumoto S, Kuroda J, Iriyama C, Yanada M, Tsukamoto N, Suehiro Y, Minami H, Garcia-Vargas J, Childs BH, Yasuda M, Masuda S, Tsujino T, Terao Y, and Tobinai K
- Subjects
- Humans, Antineoplastic Agents adverse effects, Lymphoma, Non-Hodgkin drug therapy, Lymphoma, Non-Hodgkin pathology, Neoplasm Recurrence, Local drug therapy, Quinazolines adverse effects
- Abstract
The safety, efficacy, and pharmacokinetics of copanlisib were evaluated in this phase Ib/II study in Japanese patients with relapsed/refractory indolent non-Hodgkin lymphoma (NHL). The primary endpoint was safety at the recommended dose; efficacy endpoints included objective response rate (ORR), progression-free survival (PFS), and overall survival. In phase Ib, patients received copanlisib 45 mg intravenously on days 1, 8, and 15 of a 28-day cycle, and when tolerated, consecutive patients received copanlisib 60 mg. As no dose-limiting toxicities occurred at the 45 mg (n = 3) or 60 mg (n = 7) dose in phase Ib, the recommended dose for Japanese patients was determined to be 60 mg, and this dose was used in phase II (n = 15). Although all patients experienced at least one treatment-emergent adverse event (TEAE), with hyperglycemia being the most common AE, no AE-related deaths were reported. The ORR was 68.0% (17/25 patients), median PFS was 302 (95% CI 231-484) days, and the duration of response was 330 (range 65-659) days. The pharmacokinetic properties of copanlisib were similar between Japanese and non-Japanese patients. Overall, copanlisib 60 mg had an acceptable safety profile and showed promising antitumor activity in Japanese patients with relapsed/refractory indolent NHL., (© 2022. The Author(s).)
- Published
- 2023
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7. Efficacy and safety of modified BLd therapy for Japanese patients with transplant-ineligible multiple myeloma.
- Author
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Murakami S, Ri M, Ito M, Nakamura N, Kasahara S, Kitagawa J, Inagaki Y, Kuroda J, Yoshimitsu M, Okamoto A, Fukuhara N, Taji H, Iida H, Nagai H, Hanamura I, Tsujimura H, Okura M, Kurata M, Kuwatsuka Y, Atsuta Y, and Iida S
- Subjects
- Aged, Antineoplastic Combined Chemotherapy Protocols adverse effects, Bortezomib, Dexamethasone, Humans, Japan, Lenalidomide, Treatment Outcome, Multiple Myeloma diagnosis
- Abstract
The BLd regimen, which is a triplet regimen of bortezomib (Bor), lenalidomide (Len), and dexamethasone (Dex), is effective against newly diagnosed multiple myeloma (NDMM). However, non-hematological toxicities, such as peripheral neuropathy (PN), often hamper long-term continuation of the regimen, particularly in older adult patients. In this study, we examined the efficacy and safety of the modified BLd regimen with reduced-intensity Bor and standard-dose Len. The chemotherapy regimen consisted of 1.3 mg/m
2 Bor administered subcutaneously on days 1 and 8, 25 mg Len administered on days 1-14, and 20 mg Dex on days 1-2 and 8-9 of a 3 week cycle for 8 cycles, followed by a 4 week cycle of Dex (40 mg weekly). Among the 30 patients enrolled, 60.0% (95% CI 40.6-77.3) had a very good partial response or better, and the best overall response rate was 96.7% (95% CI 82.8-99.9). Eight patients (26.7%) achieved a complete response. Grade 3 or higher PN was not observed and hematological toxicity was the most common adverse event. The modified BLd regimen showed favorable efficacy with a manageable safety profile, which suggests it could be a treatment option for transplant-ineligible NDMM., (© 2022. Japanese Society of Hematology.)- Published
- 2022
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8. Unrelated cord blood transplantation for adult-onset EBV-associated T-cell and NK-cell lymphoproliferative disorders.
- Author
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Onishi Y, Onodera K, Fukuhara N, Kato H, Ichikawa S, Fujiwara T, Yokoyama H, Yamada-Fujiwara M, and Harigae H
- Subjects
- Adult, Herpesvirus 4, Human genetics, Humans, Middle Aged, Retrospective Studies, T-Lymphocytes pathology, Young Adult, Cord Blood Stem Cell Transplantation adverse effects, Epstein-Barr Virus Infections complications, Epstein-Barr Virus Infections pathology, Hematopoietic Stem Cell Transplantation adverse effects, Lymphoproliferative Disorders etiology, Lymphoproliferative Disorders therapy, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma pathology
- Abstract
Adult-onset EBV-associated T-cell and NK-cell lymphoproliferative disorders (EBV-T/NK-LPDs) often progress rapidly, and require allogeneic stem cell transplantation early in the course of treatment. Unrelated cord blood transplantation (UCBT) is a readily available option for patients without HLA-matched donors. We retrospectively analyzed the outcomes of 12 UCBT in adult patients with chronic active EBV infection (CAEBV, n = 8), EBV-positive hemophagocytic lymphohistiocytosis following primary EBV infection (n = 2), hydroa vacciniforme-like lymphoproliferative disorder (n = 1), and systemic EBV-positive T-cell lymphoma of childhood (STCLC, n = 1). The median age at transplantation was 31.5 years (range 19-58). At the median follow-up time for survivors, which was 6.3 years (range 0.3-11.3), 3-year overall survival (OS) rates in all patients and 8 CAEBV patients were 68.2% (95% CI 28.6-88.9) and 83.3% (95% CI 27.3-97.5), respectively. Graft failure occurred in 4 of 8 CAEBV patients, requiring a second UCBT to achieve neutrophil engraftment. The cumulative incidence of grade II-IV acute GVHD was 33.3% (95% CI 9.1-60.4%). The EBV-DNA load became undetectable or very low after UCBT in all cases. UCBT may be a promising treatment option for adult-onset EBV-T/NK-LPDs., (© 2022. Japanese Society of Hematology.)
- Published
- 2022
- Full Text
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9. Phase 1/2 study of venetoclax, a BCL-2 inhibitor, in Japanese patients with relapsed or refractory chronic lymphocytic leukemia and small lymphocytic lymphoma.
- Author
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Izutsu K, Yamamoto K, Kato K, Ishikawa T, Fukuhara N, Terui Y, Choi I, Humphrey K, Kim SY, Okubo S, Ogawa N, Nishimura Y, Salem AH, and Maruyama D
- Subjects
- Adult, Aged, Antineoplastic Agents adverse effects, Antineoplastic Agents pharmacokinetics, Antineoplastic Combined Chemotherapy Protocols adverse effects, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Bridged Bicyclo Compounds, Heterocyclic administration & dosage, Bridged Bicyclo Compounds, Heterocyclic adverse effects, Bridged Bicyclo Compounds, Heterocyclic pharmacokinetics, Female, Hematologic Diseases chemically induced, Humans, Japan, Male, Middle Aged, Nausea chemically induced, Progression-Free Survival, Rituximab administration & dosage, Rituximab adverse effects, Sulfonamides administration & dosage, Sulfonamides adverse effects, Sulfonamides pharmacokinetics, Treatment Outcome, Antineoplastic Agents therapeutic use, Bridged Bicyclo Compounds, Heterocyclic therapeutic use, Leukemia, Lymphocytic, Chronic, B-Cell drug therapy, Molecular Targeted Therapy, Neoplasm Proteins antagonists & inhibitors, Proto-Oncogene Proteins c-bcl-2 antagonists & inhibitors, Sulfonamides therapeutic use
- Abstract
Patients with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) have limited treatment options. Venetoclax is a potent BCL-2 inhibitor that induces apoptosis in CLL cells. This open-label, phase 1/2 study (NCT02265731) evaluated the safety, pharmacokinetics, and efficacy of venetoclax in Japanese patients with R/R CLL/SLL. Patients enrolled in phase 1 received 400 mg/day venetoclax monotherapy. Patients enrolled in phase 2 received 400 mg/day venetoclax, plus rituximab. Venetoclax was administered with a weekly stepwise ramp-up in doses. In phase 2, efficacy was evaluated by objective response rate (ORR). Twelve patients were enrolled, six in each arm. The most common grade ≥ 3 adverse events were neutropenia (83%), lymphopenia (67%), leukopenia (33%), and thrombocytopenia (17%). Patients receiving venetoclax monotherapy achieved an ORR of 100%, including a complete remission (CR) rate of 17%. Patients receiving combination therapy had an ORR of 67% and a CR rate of 50%. The venetoclax pharmacokinetics profile in Japanese patients was similar to that of Western patients. Venetoclax 400 mg/day monotherapy or in combination with rituximab was well-tolerated and induced promising responses in Japanese patients with R/R CLL/SLL. Although patient numbers were small, the safety profile was largely consistent with other Western studies. Clinical trial registration: clinicaltrials.gov; NCT02265731.
- Published
- 2021
- Full Text
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10. Dose-adjusted EPOCH with or without rituximab for aggressive lymphoma patients: real world data.
- Author
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Matsuda S, Suzuki R, Takahashi T, Suehiro Y, Tomita N, Izutsu K, Fukuhara N, Imaizumi Y, Shimada K, Nakazato T, Yoshida I, Miyazaki K, Yamaguchi M, and Suzumiya J
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Antineoplastic Combined Chemotherapy Protocols adverse effects, Communicable Diseases epidemiology, Communicable Diseases etiology, Cyclophosphamide administration & dosage, Cyclophosphamide adverse effects, Doxorubicin administration & dosage, Doxorubicin adverse effects, Etoposide administration & dosage, Etoposide adverse effects, Feasibility Studies, Febrile Neutropenia epidemiology, Febrile Neutropenia etiology, Female, Granulocyte Colony-Stimulating Factor administration & dosage, Humans, Male, Middle Aged, Multicenter Studies as Topic, Prednisone administration & dosage, Prednisone adverse effects, Retrospective Studies, Severity of Illness Index, Treatment Outcome, Vincristine administration & dosage, Vincristine adverse effects, Young Adult, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Lymphoma drug therapy, Rituximab administration & dosage
- Abstract
CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) -/+ rituximab (R) is the standard chemotherapeutic regimen for aggressive lymphoma, but is insufficient for aggressive lymphoma with adverse prognostic factors. Dose-adjusted (DA)-EPOCH (etoposide, doxorubicin, cyclophosphamide, vincristine, and prednisolone) -/+ R demonstrates excellent efficacy against some aggressive lymphoma. Thus, we conducted a retrospective study to evaluate the feasibility and efficacy of this therapy in clinical practice. We enrolled 149 patients from 17 institutions diagnosed between 2007 and 2015. The median follow-up period for survivors was 27 months (range 0.2-123). The complete response (CR) rate of newly diagnosed patients was 79% (95% CI 68-87%). All patients were hospitalized to receive this therapy and 94% of patients also received granulocyte-colony-stimulating factor support. There were no treatment-related deaths. Febrile neutropenia (FN) and grade 3 or 4 infection occurred in 55% and 28% of patients, respectively. There were no significant differences in FN or infection between young (≤ 65 years) and elderly patients (> 65 years). In newly diagnosed diffuse large B-cell lymphoma-not otherwise specified patients (n = 46), the CR rate was 80% (95% CI 64-91%) and the 2-year OS rate was 81% (95% CI 66-90%). In the present study, DA-EPOCH -/+ R exhibited excellent efficacy and feasibility for aggressive lymphoma.
- Published
- 2020
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11. Extranasal extranodal NK/T-cell lymphoma associated with systemic lupus erythematosus.
- Author
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Ichikawa S, Fukuhara N, Shirai T, Ishii T, Ichinohasama R, and Harigae H
- Subjects
- Aged, Epstein-Barr Virus Infections complications, Female, Humans, Immunocompromised Host, Immunosuppressive Agents adverse effects, Immunosuppressive Agents therapeutic use, Lupus Erythematosus, Systemic drug therapy, Lymphoma, Extranodal NK-T-Cell diagnosis, Lymphoma, Extranodal NK-T-Cell etiology, Muscle Neoplasms diagnosis, Muscle Neoplasms etiology, Thigh, Treatment Outcome, Chemoradiotherapy, Lupus Erythematosus, Systemic complications, Lymphoma, Extranodal NK-T-Cell therapy, Muscle Neoplasms therapy
- Abstract
Increased incidence of lymphoproliferative disorders is reported in patients with autoimmune diseases, majority of which have a B-cell phenotype and are pathogenetically associated with the reactivation of Epstein-Barr virus (EBV). However, EBV-associated T/NK-cell lymphoma has hardly been reported. We present the case of a 68-year-old-woman, who had been diagnosed with systemic lupus erythematosus (SLE) 28 years back and was treated with various immunosuppressive agents including steroids, cyclophosphamide, and tacrolimus. She presented with a progressively worsening swelling of the right thigh for the last few months. Radiological examination revealed an intramuscular bulky tumor without any other lesions and the biopsy results led to a diagnosis of extranodal NK/T-cell lymphoma, nasal type (ENKL). Concurrent chemoradiotherapy resulted in a complete response, which has been sustained for more than 2 years without requiring additional therapy. After the initiation of chemotherapy, SLE did not worsen with the administration of low-dose corticosteroids. To the best of our knowledge, this is the first case report of a localized extranasal ENKL developing in a patient with SLE.
- Published
- 2020
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12. Successful treatment of methotrexate-associated classical Hodgkin lymphoma with brentuximab vedotin-combined chemotherapy: a case series.
- Author
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Ichikawa S, Fukuhara N, Saito K, Onodera K, Shirai T, Onishi Y, Yokoyama H, Fujii H, Ichinohasama R, and Harigae H
- Subjects
- Bleomycin administration & dosage, Female, Humans, Treatment Outcome, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Brentuximab Vedotin administration & dosage, Hodgkin Disease chemically induced, Hodgkin Disease drug therapy, Methotrexate adverse effects
- Abstract
Methotrexate (MTX)-associated classical Hodgkin lymphoma (CHL) is unlikely to regress following discontinuation of MTX, and its treatment usually requires chemotherapy. Standard chemotherapy for CHL is the ABVD regimen, which contains pneumotoxic bleomycin. This can be problematic in MTX-CHL patients suffering from an autoimmune disease (AID), such as rheumatoid arthritis (RA), as they frequently have pulmonary complications. However, brentuximab vedotin (BV)-containing chemotherapy without bleomycin (A + AVD regimen) was recently reported to show favorable efficacy for CHL, and could therefore be beneficial in MTX-CHL. We treated three cases of MTX-CHL using the A + AVD regimen. All were female and had received MTX for more than 15 years. Underlying AIDs in these patients were RA in two patients, and overlap syndrome with systemic lupus erythematosus and dermatomyositis in one patient. The A + AVD regimen resulted in a complete response in all patients. Peripheral neuropathy developed in two patients, necessitating reduction of the BV dose. All three patients experienced hematological toxicity necessitating dose reduction; however, no severe adverse effects, including infection or pulmonary complication, were documented. RA was well-controlled without additional immunosuppressants. The A + AVD regimen is a promising chemotherapy for MTX-CHL with favorable efficacy and tolerable toxicity profiles.
- Published
- 2020
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13. Analysis of Japanese patients from the AUGMENT phase III study of lenalidomide + rituximab (R 2 ) vs. rituximab + placebo in relapsed/refractory indolent non-Hodgkin lymphoma.
- Author
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Izutsu K, Minami Y, Fukuhara N, Terui Y, Jo T, Yamamoto G, Ishikawa T, Kobayashi T, Kiguchi T, Nagai H, Ohtsu T, Kalambakas S, Fustier P, Midorikawa S, and Tobinai K
- Subjects
- Adult, Aged, Aged, 80 and over, Double-Blind Method, Female, Humans, Male, Middle Aged, Neoplasm Recurrence, Local, Placebo Effect, Treatment Outcome, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Lenalidomide administration & dosage, Lymphoma, Non-Hodgkin drug therapy, Rituximab administration & dosage
- Abstract
Patients with indolent non-Hodgkin lymphoma (iNHL) typically respond to first-line immunochemotherapy, but relapse is common. Treatment options for relapsed iNHL include chemotherapy ± rituximab and rituximab monotherapy. Lenalidomide plus rituximab (R
2 ) is an immunomodulatory regimen that enhances rituximab-mediated cytotoxicity and improves clinical activity in iNHL. AUGMENT was a double-blind phase III randomized trial of R2 vs. rituximab + placebo (R-placebo) in patients with relapsed/refractory follicular lymphoma or marginal zone lymphoma who were not refractory to rituximab. The primary endpoint was progression-free survival (PFS). Data reported here focus on Japanese patients from AUGMENT and reflect 36 patients (n = 18, each group). PFS was superior in the R2 group, HR = 0.32 (95% CI 0.11-0.96). Median PFS was not reached (95% CI 19.7-NE) in the R2 group vs. 16.5 months (95% CI 11.3-30.6) in the R-placebo group. Grade 3/4 adverse events were more frequent in patients treated with R2 (67%) than with R-placebo (22%), primarily attributable to increased neutropenia (50% vs 17%). R2 resulted in significantly longer median PFS than R-placebo in Japanese patients with R/R iNHL, and the efficacy and the safety profile of R2 were similar to those reported in the global population.- Published
- 2020
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14. Ibrutinib in Japanese patients with relapsed/refractory B-cell malignancies: final analysis of phase I study.
- Author
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Tobinai K, Uchida T, Fukuhara N, and Nishikawa T
- Subjects
- Adenine analogs & derivatives, Asian People, Female, Follow-Up Studies, Humans, Japan, Male, Piperidines, Leukemia, Lymphocytic, Chronic, B-Cell drug therapy, Lymphoma, Mantle-Cell drug therapy, Pyrazoles administration & dosage, Pyrazoles adverse effects, Pyrimidines administration & dosage, Pyrimidines adverse effects
- Published
- 2019
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15. Bendamustine plus rituximab for previously untreated patients with indolent B-cell non-Hodgkin lymphoma or mantle cell lymphoma: a multicenter Phase II clinical trial in Japan.
- Author
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Ogura M, Ishizawa K, Maruyama D, Uike N, Ando K, Izutsu K, Terui Y, Imaizumi Y, Tsukasaki K, Suzuki K, Izumi T, Usuki K, Kinoshita T, Taniwaki M, Uoshima N, Suzumiya J, Kurosawa M, Nagai H, Uchida T, Fukuhara N, Choi I, Ohmachi K, Yamamoto G, and Tobinai K
- Subjects
- Adult, Aged, Antineoplastic Combined Chemotherapy Protocols adverse effects, Disease-Free Survival, Female, Humans, Japan, Leukopenia chemically induced, Lymphoma, B-Cell complications, Lymphoma, B-Cell mortality, Lymphoma, Mantle-Cell complications, Lymphoma, Mantle-Cell mortality, Male, Middle Aged, Neutropenia chemically induced, Remission Induction, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Bendamustine Hydrochloride administration & dosage, Lymphoma, B-Cell drug therapy, Lymphoma, Mantle-Cell drug therapy, Rituximab administration & dosage
- Abstract
A Phase II, multicenter clinical trial of bendamustine plus rituximab (BR) regimen was conducted in previously untreated patients with high-tumor-burden indolent B-cell non-Hodgkin lymphoma (B-NHL) and previously untreated elderly patients with mantle cell lymphoma (MCL) in Japan. Bendamustine 90 mg/m
2 /day on days 1 and 2, as well as rituximab 375 mg/m2 on day 1 were administered intravenously up to six cycles. The primary endpoint was the complete response (CR) rate as assessed by the International Workshop Response Criteria (1999). Sixty-nine patients (59 with indolent B-NHL and 10 with MCL) were treated. The median number of delivered cycles was six (range 1-6). The CR rates were 67.8% [95% confidence interval (CI) 54.4-79.4%] and 70.0% (95% CI 34.8-93.3%) for indolent B-NHL and MCL, respectively. Estimated progression-free survival at 30 months was 72.1% (95% CI 58.5-82.0%) in indolent B-NHL and was 67.5% (95% CI 29.1-88.2%) in MCL. Major grade 3/4 toxicities were hematologic and included lymphopenia (97%), CD4 lymphopenia (91%), neutropenia (86%), and leukopenia (83%). No treatment-related death was found. The BR regimen showed high efficacy as evidenced by the expected CR rate and durable response, as well as an acceptable safety profile for the study populations.- Published
- 2017
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16. Primary AL amyloidosis presenting with systemic lymphadenopathy with calcification.
- Author
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Fujita T, Ichikawa S, Okitsu Y, Fukuhara N, Yoshinaga T, Yazaki M, and Harigae H
- Subjects
- Aged, Amyloidosis pathology, Calcinosis pathology, Humans, Immunoglobulin Light-chain Amyloidosis, Lymphadenopathy pathology, Male, Plasma Cells pathology, Amyloidosis complications, Calcinosis complications, Lymph Nodes pathology, Lymphadenopathy complications
- Published
- 2016
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17. Inhibition of human primary megakaryocyte differentiation by anagrelide: a gene expression profiling analysis.
- Author
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Sakurai K, Fujiwara T, Hasegawa S, Okitsu Y, Fukuhara N, Onishi Y, Yamada-Fujiwara M, Ichinohasama R, and Harigae H
- Subjects
- Cell Differentiation genetics, Cells, Cultured, Fetal Blood cytology, Humans, Megakaryocyte Progenitor Cells cytology, Platelet Aggregation Inhibitors pharmacology, Transcription Factors genetics, Cell Differentiation drug effects, Gene Expression Profiling, Megakaryocytes cytology, Quinazolines pharmacology
- Abstract
Anagrelide is a treatment option for patients with essential thrombocythemia. Although the clinical efficacy of anagrelide has been established, there is limited knowledge of the molecular mechanism underlying its effect. Here, we evaluated the effect of anagrelide on primary megakaryocytic progenitors from cord blood-derived CD34-positive cells. Anagrelide treatment reduced the expression of megakaryocytic markers (CD41 and CD61). Microarray analysis was performed to characterize gene profiles altered by exposure to anagrelide. The analysis demonstrated upregulation and downregulation (>2-fold) of eight and 34 genes, respectively, in anagrelide-treated megakaryocyte progenitors. This included genes encoding prototypical megakaryocytic proteins, such as PPBP, PF4, and GP6. Gene ontology analysis of genes suppressed by anagrelide treatment revealed significant enrichment of genes involved in platelet activation and degranulation. Expression levels of transcription factors involved in megakaryocyte commitment/differentiation were further evaluated by quantitative RT-PCR, demonstrating significant downregulation of FLI1 and TAL1 in anagrelide-treated megakaryocyte progenitors. Knockdown of TAL1 in primary megakaryocyte progenitors confirmed significant downregulation of FLI1 and megakaryocytic genes. Anagrelide had no significant effect on the surface expression of erythroid markers or on the expression of transcription factors involved in erythroid commitment/differentiation. In conclusion, anagrelide suppresses megakaryocytic differentiation, partly through decreasing the expression of megakaryocytic transcription factors.
- Published
- 2016
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18. Identification of a novel putative mitochondrial protein FAM210B associated with erythroid differentiation.
- Author
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Kondo A, Fujiwara T, Okitsu Y, Fukuhara N, Onishi Y, Nakamura Y, Sawada K, and Harigae H
- Subjects
- Cell Line, Erythroblasts metabolism, Erythroid Cells metabolism, GATA1 Transcription Factor genetics, Gene Expression Regulation, Developmental, HEK293 Cells, Humans, Introns, Membrane Proteins genetics, Mitochondrial Proteins genetics, RNA Interference, RNA, Small Interfering genetics, Erythroblasts cytology, Erythroid Cells cytology, Erythropoiesis, GATA1 Transcription Factor metabolism, Membrane Proteins metabolism, Mitochondrial Proteins metabolism
- Abstract
The transcription factor GATA-1 plays an essential role in erythroid differentiation. To identify novel GATA-1 target genes, we analyzed a merged ChIP-seq and expression profiling dataset. We identified FAM210B as a putative novel GATA-1 target gene. Study results demonstrated that GATA-1 directly regulates FAM210B expression, presumably by binding to an intronic enhancer region. Both human and murine FAM210B are abundantly expressed in the later stages of erythroblast development. Moreover, the deduced amino acid sequence predicted that FAM210B is a membrane protein, and Western blot analysis demonstrated its mitochondrial localization. Loss-of-function analysis in erythroid cells suggested that FAM210B may be involved in erythroid differentiation. The identification and characterization of FAM210B provides new insights in the study of erythropoiesis and hereditary anemias.
- Published
- 2016
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