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Real-world data from yttrium-90 ibritumomab tiuxetan treatment of relapsed or refractory indolent B-cell non-Hodgkin's lymphoma: J3Zi Study

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Abstract

Yttrium-90 ibritumomab tiuxetan (90YIT) is a radioimmunotherapy agent in which the radioisotope yttrium-90 is bound to ibritumomab via tiuxetan as a chelating agent, and is used for relapsed or refractory low-grade B-cell non-Hodgkin's lymphoma (rr-B-NHL). We conducted a joint study to evaluate the clinical outcome of 90YIT. The J3Zi study is composed of data from patients receiving 90YIT for rr-B-NHL from the top three institutions with 10 years of 90YIT treatment experience from October 2008 to May 2018 in Japan. The efficacy, prognostic factors and safety of 90YIT were retrospectively evaluated. Data from 316 patients were analyzed; the mean age was 64.6 years and the median number of prior treatments was 2. The median PFS was 3.0 years, the final OS rate was over 60%, and the median OS was not reached during the study period. Significant factors influencing PFS were sIL-2R ≤ 500 (U/mL) and no disease progression within 24 months of first treatment. Significant factors influencing OS were number of prior treatments ≤ 2 and sIL-2R ≤ 500 (U/mL). The PFS and OS rates were found to be significantly higher in the late half era (2013 to 2018) than in the early half era (2008 to 2013) during the study period. Prognosis following 90YIT treatment was improved in the late half era compared to the early half era. As treatment using 90YIT increased, administration of 90YIT shifted to the earlier treatment line. This may have contributed to the improvement of prognosis found in the late era. (UMIN000037105).

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Data Availability

The original data are available by e-mail from the corresponding author on reasonable request and provision of data must be in compliance with the relevant legal regulations.

References

  1. Cancer statistics Japan (in Japanese). https://ganjoho.jp/reg_stat/statistics/stat/cancer/25_ml.html. Accessed 22 Sep 2022

  2. Lymphoma Study Group of Japanese Pathologists (2000) The world health organization classification of malignant lymphomas in japan: incidence of recently recognized entities. Pathol Int 50:696–702. https://doi.org/10.1046/j.1440-1827.2000.01108.x

    Article  Google Scholar 

  3. Susanibar-Adaniya S, Barta SK (2021) 2021 Update on Diffuse large B cell lymphoma: A review of current data and potential applications on risk stratification and management. Am J Hematol 96:617–629. https://doi.org/10.1002/ajh.26151

    Article  PubMed  PubMed Central  Google Scholar 

  4. Reddy S, Saxena VS, Pellettiere EV, Hendrickson FR (1989) Stage I and II non-Hodgkin’s lymphomas: long-term results of radiation therapy. Int J Radiat Oncol Biol Phys 16:687–692. https://doi.org/10.1016/0360-3016(89)90486-0

    Article  CAS  PubMed  Google Scholar 

  5. Mac Manus MP, Hoppe RT (1996) Is radiotherapy curative for stage I and II low-grade follicular lymphoma? Results of a long-term follow-up study of patients treated at Stanford University. J Clin Oncol 14:1282–90. https://ascopubs.org/doi/10.1200/JCO.1996.14.4.1282. Accessed 30 Sept 2022

  6. Grossbard ML, Press OW, Appelbaum FR et al (1992) Monoclonal antibody-based therapies of leukemia and lymphoma. Blood 80:863

    Article  CAS  PubMed  Google Scholar 

  7. Witzig TE, Hong F, Micallef IN et al (2015) A phase II trial of RCHOP followed by radioimmunotherapy for early stage (stages I/II) diffuse large B-cell non-Hodgkin lymphoma: ECOG3402. Br J Haematol 170:679–686. https://doi.org/10.1111/bjh.13493

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Candelaria M, Dueñas-Gonzalez A (2021) Rituximab in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in diffuse large B-cell lymphoma. Ther Adv Hematol 12:2040620721989579. https://doi.org/10.1177/2040620721989579

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Tobinai K, Watanabe T, Ogura M et al (2009) Japanese phase II study of 90Y-ibritumomab tiuxetan in patients with relapsed or refractory indolent B-cell lymphoma. Cancer Sci 100:158–164. https://doi.org/10.1111/j.1349-7006.2008.00999.x

    Article  CAS  PubMed  Google Scholar 

  10. Uike N, Choi I, Tsuda M et al (2014) Factors associated with effects of 90Y-ibritumomab tiuxetan in patients with relapsed or refractory low-grade B cell non-Hodgkin lymphoma: single-institution experience with 94 Japanese patients in rituximab era. Int J Hematol 100:386–392. https://doi.org/10.1007/s12185-014-1636-5

    Article  CAS  PubMed  Google Scholar 

  11. Yoshikawa H, Sakurashita H, Izumitani S, Taogoshi T, Saeki Y, Matsuo H (2019) Safety of 90Y-ibritumomab Tiuxetan treatment for Japanese patients in real-world clinical practice. Yakugaku Zasshi 139:131–134. https://doi.org/10.1248/yakushi.18-00112

    Article  CAS  PubMed  Google Scholar 

  12. Batlevi CL, Sha F, Alperovich A et al (2020) Follicular lymphoma in the modern era: survival, treatment outcomes, and identification of high-risk subgroups. Blood Cancer J 10:74. https://doi.org/10.1038/s41408-020-00340-z

    Article  PubMed  PubMed Central  Google Scholar 

  13. Emmanouilides C, Witzig TE, Gordon LI et al (2006) Treatment with yttrium 90 ibritumomab tiuxetan at early relapse is safe and effective in patients with previously treated B-cell non-Hodgkin’s lymphoma. Leuk Lymphoma 47:629–636. https://doi.org/10.1080/10428190500376076

    Article  CAS  PubMed  Google Scholar 

  14. Yoshida N, Oda M, Kuroda Y et al (2013) Clinical significance of sIL-2R levels in B-cell lymphomas. PLoS One 8:e78730. https://doi.org/10.1371/journal.pone.0078730

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Nakase K, Tsuji K, Tamaki S et al (2005) Elevated levels of soluble interleukin-2 receptor in serum of patients with hematological or non-hematological malignancies. Cancer Detect Prev 29:256–259. https://doi.org/10.1016/j.cdp.2005.03.001

    Article  CAS  PubMed  Google Scholar 

  16. Umino K, Fujiwara SI, Ikeda T et al (2017) Prognostic value of the soluble interleukin-2 receptor level after patients with follicular lymphoma achieve a response to R-CHOP. Hematology 22:521–526. https://doi.org/10.1080/10245332.2017.1312204

    Article  CAS  PubMed  Google Scholar 

  17. Yoshizato T, Nannya Y, Imai Y, Ichikawa M, Kurokawa M (2013) Clinical significance of serum-soluble interleukin-2 receptor in patients with follicular lymphoma. Clin Lymphoma Myeloma Leuk 13:410–416. https://doi.org/10.1016/j.clml.2013.03.014

    Article  CAS  PubMed  Google Scholar 

  18. Ohno H, Ishikawa T, Kitajima H et al (2002) Significance of soluble interleukin-2 receptor alpha chain in the management of patients with malignant lymphoma: a multi-center study. Rinsho Ketsueki 43:170–175 (in Japanese)

    PubMed  Google Scholar 

  19. Morrison VA, Shou Y, Bell JA et al (2019) Treatment Patterns and Survival Outcomes in Patients With Follicular Lymphoma: A 2007 to 2015 Humedica Database Study. Clin Lymphoma Myeloma Leuk 19:e172–e183. https://doi.org/10.1016/j.clml.2018.12.017

    Article  PubMed  Google Scholar 

  20. Bachy E, Rufibach K, Parreira J, Launonen A, Nielsen T, Hackshaw A (2021) Phase III clinical trials in first-line follicular lymphoma: A review of their design and interpretation. Adv Ther 38:3489–3505. https://doi.org/10.6084/m9.figshare.14381117

    Article  PubMed  PubMed Central  Google Scholar 

  21. Casulo C, Byrtek M, Dawson KL et al (2015) Early relapse of follicular lymphoma after rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone defines patients at high risk for death: an analysis from the national lymphocare study. J Clin Oncol 33:2516–22. https://ascopubs.org/doi/full/10.1200/JCO.2014.59.7534. Accessed 30 Sept 2022

  22. Zinzani PL, Tani M, Pulsoni A et al (2012) A phase II trial of short course fludarabine, mitoxantrone, rituximab followed by 90Y-ibritumomab tiuxetan in untreated intermediate/high-risk follicular lymphoma. Ann Oncol 23:415–420. https://doi.org/10.1093/annonc/mdr145

    Article  CAS  PubMed  Google Scholar 

  23. Zinzani PL, Tani M, Pulsoni A et al (2008) Fludarabine and mitoxantrone followed by yttrium-90 ibritumomab tiuxetan in previously untreated patients with follicular non-Hodgkin lymphoma trial: a phase II non-randomised trial (FLUMIZ). Lancet Oncol 9:352–358. https://doi.org/10.1016/S1470-2045(08)70039-1

    Article  CAS  PubMed  Google Scholar 

  24. Hainsworth JD, Spigel DR, Markus TM et al (2009) Rituximab plus short-duration chemotherapy followed by Yttrium-90 Ibritumomab tiuxetan as first-line treatment for patients with follicular non-Hodgkin lymphoma: a phase II trial of the Sarah Cannon Oncology Research Consortium. Clin Lymphoma Myeloma 9:223–228. https://doi.org/10.3816/CLM.2009.n.044

    Article  CAS  PubMed  Google Scholar 

  25. Nakagawa M, Uike N, Choi I, Hayashi T, Uehara S (2012) Efficacy and safety of yttrium-90 ibritumomab tiuxetan in Japanese patients with non-Hodgkin lymphoma. Jpn J Radiol 30:642–647. https://doi.org/10.1007/s11604-012-0103-6

    Article  CAS  PubMed  Google Scholar 

  26. Wiseman GA, Gordon LI, Multani PS et al (2002) Ibritumomab tiuxetan radioimmunotherapy for patients with relapsed or refractory non-Hodgkin lymphoma and mild thrombocytopenia: a phase II multicenter trial. Blood 99:4336. https://doi.org/10.1182/blood.V99.12.4336

    Article  CAS  PubMed  Google Scholar 

  27. Emmanouilides C, Witzig TE, Wiseman GA et al (2007) Safety and efficacy of yttrium-90 ibritumomab tiuxetan in older patients with non-Hodgkin’s lymphoma. Cancer Biother Radiopharm 22:684. https://doi.org/10.1089/cbr.2007.359

    Article  PubMed  Google Scholar 

  28. Pfreundschuh M (2017) Age and sex in Non-Hodgkin lymphoma therapy: it’s not all created equal, or is it? Am Soc Clin Oncol Educ Book 37:505–511. https://ascopubs.org/doi/pdf/10.1200/EDBK_175447. Accessed 30 Sept 2022

  29. Czuczman MS, Emmanouilides C, Darif M, Witzig TE, Gordon LI, Revell S, Vo K, Molina A (2007) Treatment-related myelodysplastic syndrome and acute myelogenous leukemia in patients treated with ibritumomab tiuxetan radioimmunotherapy. J Clin Oncol 25(27):4285–4292

    Article  CAS  PubMed  Google Scholar 

  30. Epperla N, Pham AQ, Burnette BL, Wiseman GA, Habermann TM, Macon WR, Ansell SM, Inwards DJ, Micallef IN, Johnston PB, Markovic SN, Porrata LF, Colgan JP, Ristow KM, Nowakowski GS, Witzig TE (2017) Risk of histological transformation and therapy-related myelodysplasia/acute myeloid leukaemia in patients receiving radioimmunotherapy for follicular lymphoma. Br J Haematol 178(3):427–433

    Article  CAS  PubMed  Google Scholar 

  31. Hosing C, Munsell M, Yazji S, Andersson B, Couriel D, de Lima M, Donato M, Gajewski J, Giralt S, Körbling M, Martin T, Ueno NT, Champlin RE, Khouri IF (2002) Risk of therapy-related myelodysplastic syndrome/acute leukemia following high-dose therapy and autologous bone marrow transplantation for non-Hodgkin’s lymphoma. Ann Oncol 13(3):450–459

    Article  CAS  PubMed  Google Scholar 

  32. Sacchi S, Marcheselli L, Bari A et al (2008) Secondary malignancies after treatment for indolent non-Hodgkin’s lymphoma: a 16-year follow-up study. Haematologica 93:398–404. https://doi.org/10.3324/haematol.12120

    Article  PubMed  Google Scholar 

  33. Di M, Ollila TA, Olszewski AJ (2020) Exposure to ibritumomab tiuxetan and incidence of treatment-related myeloid neoplasms among older patients with B-cell lymphoma: a population-based study. Leukemia 34:2794–2797. https://www.nature.com/articles/s41375-020-0798-9. Accessed 30 Sept 2022

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Funding

This study was supported by a research grant from Mundipharma K.K., Tokyo, Japan.

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Authors and Affiliations

  1. Department of Hematology, National Hospital Organization Kyushu Cancer Center, 3-1-1 Notame, Minami-Ku, Fukuoka City, Fukuoka, 811-1395, Japan

    Ilseung Choi

  2. Department of Hematology, Hyogo College of Medicine Hospital, Nishinomiya City, Hyogo, Japan

    Masaya Okada

  3. First Department of Internal Medicine, Kansai Medical University, Hirakata City, Osaka, Japan

    Tomoki Ito

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  1. Ilseung Choi
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  2. Masaya Okada
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All authors contributed equally to this work and approved the final manuscript.

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Correspondence to Ilseung Choi.

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Ethical approval

This study was conducted in accordance with the ethical principles of the Declaration of Helsinki and the Ethical Guidelines for Medical and Health Research Involving Human Subjects established by the Ministry of Health, Labor, and Welfare in Japan. The study protocol was approved by the ethics committees in the all participating institutions.

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Informed consent was not required as this study was a retrospective study.

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Choi, I., Okada, M. & Ito, T. Real-world data from yttrium-90 ibritumomab tiuxetan treatment of relapsed or refractory indolent B-cell non-Hodgkin's lymphoma: J3Zi Study. Ann Hematol 102, 1149–1158 (2023). https://doi.org/10.1007/s00277-023-05157-x

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