Annual Report 2023
Department of Hematology
Koji Izutsu, Tatsuya Suzuki, Wataru Munakata, Suguru Fukuhara, Noriko Iwaki, Shinichi Makita, Haruhi Makino, Tetsuro Ochi
Introduction
The Department of Hematology of the National Cancer Center Hospital is dedicated to supporting patients with hematologic malignancies including leukemia, lymphoma, and myeloma by offering state-of-the-art diagnosis and treatment options and developing novel treatment and diagnostic methods through clinical trials and translational research. Our Lymphoma Program has a history of pioneering clinical research on adult T-cell leukemia/ lymphoma and other lymphoid malignancies, and has been leading the development of novel agents and cellular therapies for hematologic malignancies in Japan.
The Team and What We Do
We offer the most advanced diagnostic procedures and care for patients with hematologic malignancies (e.g., leukemia, lymphoma, myelodysplastic syndrome, and multiple myeloma), both on an outpatient and inpatient basis (Table 1). The medical treatments we offer include chemotherapy, immunotherapy, and chimeric antigen receptor (CAR) T-cell therapy. We treat patients in collaboration with experts from our center's Department of Hematopoietic Stem Cell Transplantation, Department of Radiation Oncology, and Department of Experimental Therapeutics. Moreover, experts at our center's Department of Pathology and Department of Clinical Laboratories offer state-of-the-art diagnosis to guide treatment.
Research Activities
We are conducting clinical trials of new treatments for hematological malignancies. Clinical trials include global first-in-human studies, global phase 2-3 studies, and domestic phase 1-3 studies. We are also conducting investigator-initiated clinical trials. In 2023, we completed enrolment of our investigator-initiated phase 2 study of atezolizumab monotherapy in patients with relapsed/refractory extranodal NK/T-cell lymphoma. In 2018, in collaboration with other departments, we launched the MASTER KEY HEM registration study for rare hematologic malignancies incorporating biomarkers. Our department is dedicated to the activities of the leading clinical study groups for hematological malignancies in Japan, namely, the Japan Clinical Oncology Group - Lymphoma Study Group (JCOG LSG) and the Japan Adult Leukemia Study Group (JALSG). This year, we authored or coauthored 34 articles related to hematological malignancies.
Clinical Trials
In 2023, we conducted 59 corporate-sponsored clinical trials, including many global studies, one first-in-human study, and 6 new studies that started from April 2023 to March 2024. We also conducted several investigator-initiated clinical trials of JCOG and JALSG.
Education
We have been offering a training program for young hematologists and/or oncologists. Many of our graduates are actively engaged in hematology and oncology societies.
Future Prospects
The Department of Hematology will continue to address unmet needs in the treatment of hematological malignancies. We are focusing on developing treatments for rare hematologic malignancies including rare subtypes of lymphoma. Our future plans include genome-based medicine. Information obtained from genomic tests has become imperative in the diagnosis according to the current WHO classification of hematologic malignancies, prognosis prediction, and for guiding selection of molecular-targeted agents.
List of papers published in 2023
Journal
1. Watanabe T, Tobinai K, Wakabayashi M, Maruyama D, Yamamoto K, Kubota N, Shimada K, Asagoe K, Yamaguchi M, Ando K, Ogura M, Kuroda J, Suehiro Y, Matsuno Y, Tsukasaki K, Nagai H. R-CHOP treatment for patients with advanced follicular lymphoma: Over 15-year follow-up of JCOG0203. British journal of haematology, 204:849-860, 2024
2. Sugiyama M, Arakawa A, Kogure Y, Shirakawa N, Watanabe M, Ito Y, Tanimura K, Tao K, Nakajima M, Watanabe Y, Miyagi-Maeshima A, Fukuhara S, Kataoka K, Izutsu K, Fukuda T, Ogawa C. Different phenotype relapse of myeloid/lymphoid neoplasms with FGFR1 rearrangement with long remission. Pediatric blood & cancer, 71:e30721, 2024
3. Makita S, Ota S, Mishima Y, Usuki K, Ennishi D, Yanada M, Fukuhara N, Yamamoto R, Takamine A, Nohara G, Izutsu K. 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. International journal of hematology, 119:156-163, 2024
4. Goto H, Ito S, Kizaki M, Yamaguchi M, Fukuhara N, Kato K, Saito T, Terui Y, Okubo S, Soshin T, Zeng J, Honda H, Badawi M, Ross JA, Izutsu K. Phase 2 study of ibrutinib plus venetoclax in Japanese patients with relapsed/refractory mantle cell lymphoma. International journal of clinical oncology, 29:232-240, 2024
5. Maruyama D, Omi A, Nomura F, Touma T, Noguchi Y, Takebe K, Izutsu K. Real-world effectiveness and safety of ibrutinib in relapsed/refractory mantle cell lymphoma in Japan: post-marketing surveillance. International journal of hematology, 119:146-155, 2024
6. Saito T, Nagai H, Izutsu K, Ando K, Igarashi T, Izumi T, Ohashi Y, Kamiyama S, Ishizawa K, Tobinai K. A phase II Japanese trial of 90-minute rituximab infusion for untreated B-cell lymphoma. Japanese journal of clinical oncology, 54:444-451, 2024
7. Izutsu K, Ubukawa K, Morishita T, Onishi Y, Ishizawa K, Fujii Y, Kimura N, Yokochi M, Naoe T. Glasdegib with intensive/nonintensive chemotherapy in Japanese patients with untreated acute myeloid leukemia or high-risk myelodysplastic syndromes. Cancer science, 115:1250-1260, 2024
8. Kaimi Y, Takahashi Y, Taniguchi H, Ochi T, Makino H, Makita S, Iwaki N, Fukuhara S, Munakata W, Ogawa C, Izutsu K, Maeshima AM. Loss of or decrease in CD30 expression in four patients with anaplastic large cell lymphoma after brentuximab vedotin-containing therapy. Virchows Archiv, 484:465-473, 2024
9. O'Connor OA, Ko BS, Wang MC, Maruyama D, Song Y, Yeoh EM, Manamley N, Tobinai K. Pooled Analysis of Pralatrexate Single-Agent Studies in Patients With Relapsed/Refractory Peripheral T-Cell Lymphoma. Blood advances, 8:2601-2611, 2024
10. Takizawa J, Suzuki R, Izutsu K, Kiguchi T, Asaoku H, Saburi Y, Masunari T, Utsunomiya A, Takeuchi K, Nakamura N, Ohshima K, Gruber M, Jäger U, Aoki S, Suzumiya J. Characteristics of chronic lymphocytic leukemia in Japan: Comprehensive analysis of the CLLRSG-01 study. International journal of hematology, 119:686-696, 2024
11. Yamaguchi K, Yamamoto H, Izutsu K, Yuasa M, Kaji D, Nishida A, Ishiwata K, Takagi S, Yamamoto G, Asano-Mori Y, Uchida N, Taniguchi S. Fatal outcome of BK virus encephalitis in an allogeneic stem cell transplantation recipient. Journal of infection and chemotherapy, 30:1166-1169, 2024
12. Kato K, Izutsu K, Nishikori M, Shibayama H, Maeda Y, Yoshimura K, Tateishi U, Miyamoto T, Matsuda Y, Ishikawa J, Rai S, Takahashi T, Yamauchi T, Matsumura I, Akashi K, Kanakura Y, Suzumiya J. End-of-treatment 18[F]-FDG PET can predict early progression in patients receiving bendamustine-rituximab for follicular lymphoma in first relapse: a prospective West Japan hematology Study Group (W-JHS) NHL01 trial. International journal of hematology, 119:677-685, 2024
13. Kawasaki A, Hatake K, Matsumura I, Izutsu K, Hoshino T, Akamatsu A, Kakuuchi A, Tobinai K. Post-marketing surveillance of the safety and effectiveness of nivolumab for classic Hodgkin lymphoma in Japan. International journal of hematology, 119:667-676, 2024
14. Abramson JS, Solomon SR, Arnason J, Johnston PB, Glass B, Bachanova V, Ibrahimi S, Mielke S, Mutsaers P, Hernandez-Ilizaliturri F, Izutsu K, Morschhauser F, Lunning M, Crotta A, Montheard S, Previtali A, Ogasawara K, Kamdar M. Plain language summary of the TRANSFORM study primary analysis results: liso-cell as a second treatment regimen for large B-cell lymphoma following failure of the first treatment regimen. Future oncology 20:1455-1456, 2024
15. Ogura M, Yamamoto K, Morishima Y, Wakabayashi M, Tobinai K, Ando K, Uike N, Kurosawa M, Gomyo H, Taniwaki M, Nosaka K, Tsukamoto N, Shimoyama T, Fukuhara N, Yakushijin Y, Ohnishi K, Miyazaki K, Kameoka Y, Takayama N, Hanamura I, Kobayashi H, Usuki K, Kobayashi N, Ohyashiki K, Utsumi T, Kumagai K, Maruyama D, Ohmachi K, Matsuno Y, Nakamura S, Hotta T, Tsukasaki K, Nagai H. Long-term follow-up after R-High CHOP/CHASER/LEED with Auto-PBSCT in untreated mantle cell lymphoma-Final analysis of JCOG0406. Cancer science, 114:3461-3465, 2023
16. Takahashi Y, Taniguchi H, Haruhi F, Hattori D, Sasaki H, Makita S, Iwaki N, Fukuhara S, Munakata W, Saito Y, Izutsu K, Maeshima AM. Pathogenesis of Gastrointestinal Follicular Lymphomas: Consideration Based on Histopathology and Endoscopic Findings. The American journal of surgical pathology, 47:1134-1143, 2023
17. Abramson JS, Solomon SR, Arnason J, Johnston PB, Glass B, Bachanova V, Ibrahimi S, Mielke S, Mutsaers P, Hernandez-Ilizaliturri F, Izutsu K, Morschhauser F, Lunning M, Crotta A, Montheard S, Previtali A, Ogasawara K, Kamdar M. Lisocabtagene maraleucel as second-line therapy for large B-cell lymphoma: primary analysis of the phase 3 TRANSFORM study. Blood, 141:1675-1684, 2023
18. Munakata W, Ando K, Yokoyama M, Fukuhara N, Yamamoto K, Fukuhara S, Ohmachi K, Mishima Y, Ichikawa S, Ogiya D, Aoi A, Hatsumichi M, Tobinai K. Long-term safety profile of tirabrutinib: final results of a Japanese Phase I study in patients with relapsed or refractory B-cell malignancies. International journal of hematology, 117:553-562, 2023
19. Song Y, Tilly H, Rai S, Zhang H, Jin J, Goto H, Terui Y, Shin HJ, Kim WS, Cao J, Feng J, Eom HS, Kim TM, Tsai XC, Gau JP, Koh H, Zhang L, Song Y, Yang Y, Li W, Huang H, Ando K, Sharman JP, Sehn LH, Bu L, Wang X, Jiang Y, Hirata J, Lee C, Zhu J, Izutsu K. Polatuzumab vedotin in previously untreated DLBCL: an Asia subpopulation analysis from the phase 3 POLARIX trial. Blood, 141:1971-1981, 2023
20. Kim WS, Fukuhara N, Yoon DH, Yamamoto K, Uchida T, Negoro E, Izutsu K, Terui Y, Nakajima H, Ando K, Suehiro Y, Kang HJ, Ko PS, Nagahama F, Sonehara Y, Nagai H, Tien HF, Kwong YL, Tobinai K. Darinaparsin in patients with relapsed or refractory peripheral T-cell lymphoma: results of an Asian phase 2 study. Blood advances, 7:4903-4912, 2023
21. Maeshima AM, Taniguchi H, Furukawa H, Hattori D, Sasaki H, Makita S, Iwaki N, Fukuhara S, Munakata W, Izutsu K. Diagnostic clues of BCL2-negative, faint, or controversial follicular lymphomas: a study of 103 cases. Human pathology, 135:84-92, 2023
22. Hosono N, Chi S, Yamauchi T, Fukushima K, Shibayama H, Katagiri S, Gotoh A, Eguchi M, Morishita T, Ogasawara R, Kondo T, Yanada M, Yamamoto K, Kobayashi T, Kuroda J, Usuki K, Utsu Y, Yoshimitsu M, Ishitsuka K, Ono T, Takahashi N, Iyama S, Kojima K, Nakamura Y, Fukuhara S, Izutsu K, Abutani H, Yamauchi N, Yuda J, Minami Y. Clinical utility of genomic profiling of AML using paraffin-embedded bone marrow clots: HM-SCREEN-Japan 01. Cancer science, 114:2098-2108, 2023
23. Tao K, Inamoto Y, Furukawa H, Hosoba R, Takeda W, Maeshima A, Aoki J, Ito A, Tanaka T, Kim SW, Makita S, Fukuhara S, Kogure Y, Kataoka K, Izutsu K, Fukuda T. Romidepsin-induced durable remission for relapsed nodal peripheral T-cell lymphoma with T follicular helper phenotype after allogeneic hematopoietic cell transplantation. International journal of hematology, 118:292-298, 2023
24. Miyazaki K, Sakai R, Iwaki N, Yamamoto G, Murayama K, Nishikori M, Sunami K, Yoshida I, Yano H, Takahashi N, Okamoto A, Munemoto S, Sawazaki A, Suehiro Y, Fukuhara N, Wake A, Arai A, Masaki Y, Toyama K, Yokoyama A, Tsunemine H, Hasegawa Y, Matsumoto K, Yamada T, Nishimura Y, Tamaru S, Asano N, Miyawaki K, Izutsu K, Kinoshita T, Suzuki R, Ohshima K, Kato K, Katayama N, Yamaguchi M. Five-year follow-up of a phase II study of DA-EPOCH-R with high-dose MTX in CD5-positive DLBCL. Cancer science, 114:2689-2691, 2023
25. Canales MA, Buchholz TA, Bortolini JAP, Fogliatto LM, Ishikawa T, Izutsu K, Salar A, Sharman JP, Klingbiel D, Pokala S, Vorozheikina E, Trask P, Parreira J, Hübel K. Obinutuzumab Can Be Administered as a 90-minute Short Duration Infusion in Patients With Previously Untreated Follicular Lymphoma: GAZELLE End of Induction Analysis. HemaSphere, 7:e860, 2023
26. Wai KM, Akuzawa R, Umeda Y, Munakata W, Takahashi Y, Nakaji S, Ihara K. Effects of body compositions on the associations between ferritin and diabetes parameters among Japanese community dwellers. Journal of trace elements in medicine and biology, 78:127174, 2023
27. Wang ML, Jurczak W, Zinzani PL, Eyre TA, Cheah CY, Ujjani CS, Koh Y, Izutsu K, Gerson JN, Flinn I, Tessoulin B, Alencar AJ, Ma S, Lewis D, Lech-Maranda E, Rhodes J, Patel K, Maddocks K, Lamanna N, Wang Y, Tam CS, Munir T, Nagai H, Hernandez-Ilizaliturri F, Kumar A, Fenske TS, Seymour JF, Zelenetz AD, Nair B, Tsai DE, Balbas M, Walgren RA, Abada P, Wang C, Zhao J, Mato AR, Shah NN. Pirtobrutinib in Covalent Bruton Tyrosine Kinase Inhibitor Pretreated Mantle-Cell Lymphoma. Journal of clinical oncology, 41:3988-3997, 2023
28. Munakata W, Izutsu K, Mishima Y, Nagai H, Ishihara Y, Suzumiya J, Kanakura Y, Nanki T, Miyake T, Kawasaki A, Yoshinaga T, Ishizawa K. Dose-escalation part of Phase I study of single-agent mosunetuzumab in Japanese patients with relapsed/refractory B-cell non-Hodgkin lymphoma. Japanese journal of clinical oncology, 53:912-921, 2023
29. Sugitani A, Fukuhara S, Shibata M, Ichihara R, Furukawa H, Maeshima AM. Diffuse large B-cell lymphoma with composite germinal center and non-germinal center types: A report of two cases. Journal of clinical and experimental hematopathology, 63:181-186, 2023
30. 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, Maruyama D. Measurable residual disease in Japanese patients with relapsed or refractory chronic lymphocytic leukemia treated with venetoclax. International journal of hematology, 118:526-528, 2023
31. Makiyama J, Ishitsuka K, Munakata W, Maruyama D, Nagai H. An update on the developments in the treatment of adult T-cell leukemia-lymphoma: current knowledge and future perspective. Japanese journal of clinical oncology, 53:1104-1111, 2023
32. Nastoupil LJ, Hess G, Pavlovsky MA, Danielewicz I, Freeman J, García-Sancho AM, Glazunova V, Grigg A, Hou JZ, Janssens A, Kim SJ, Masliak Z, McKay P, Merli F, Munakata W, Nagai H, Özcan M, Preis M, Wang T, Rowe M, Tamegnon M, Qin R, Henninger T, Curtis M, Caces DB, Thieblemont C, Salles G. Phase 3 SELENE study: ibrutinib plus BR/R-CHOP in previously treated patients with follicular or marginal zone lymphoma. Blood advances, 7:7141-7150, 2023
33. Yang Y, Mori M, Wai KM, Jiang T, Sugimura Y, Munakata W, Mikami T, Murashita K, Nakaji S, Ihara K. The Association between Gut Microbiota and Depression in the Japanese Population. Microorganisms, 11:2286, 2023
34. Izutsu K, Kumode T, Yuda J, Nagai H, Mishima Y, Suehiro Y, Yamamoto K, Fujisaki T, Ishitsuka K, Ishizawa K, Ikezoe T, Nishikori M, Akahane D, Fujita J, Dinh M, Soong D, Noguchi H, Buchbjerg JK, Favaro E, Fukuhara N. Subcutaneous epcoritamab monotherapy in Japanese adults with relapsed/refractory diffuse large B-cell lymphoma. Cancer science, 114:4643-4653, 2023