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Lymphoma

Exposure to ibritumomab tiuxetan and incidence of treatment-related myeloid neoplasms among older patients with B-cell lymphoma: a population-based study

Leukemia volume 34, pages 2794–2797 (2020)Cite this article

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Ibritumomab tiuxetan (IbT) is a radioimmunoconjugate linking the anti-CD20 antibody rituximab with the radioactive yttrium isotope 90Y. IbT is approved for treatment of relapsed or refractory indolent B-cell lymphomas, and for consolidation after chemotherapy in follicular lymphoma [1]. In the relapsed/refractory setting, IbT results in a response rate of 80% and median duration response of 14 months [2]. Furthermore, ~37% of patients achieve long-term responses with median time to progression of 29 months [3]. The use of IbT in follicular lymphoma as consolidation following first-line chemotherapy extended median progression-free survival (from 1.1 to 4.1 years) and time to next treatment (from 3.0 to 8.1 years) in the pre-rituximab era [4]. Despite this efficacy, application of IbT has been limited by concerns about treatment-related myeloid neoplasms (t-MN, including myelodysplastic syndrome and acute myeloid leukemia) as a consequence of diffuse irradiation of the bone marrow. t-MN have been also observed after the iodine I131-containing radioimmunoconjugate tositumomab [5]. In a pooled analysis of clinical trials, the crude incidence of t-MN after IbT therapy was 2.5%, but single-institution retrospective case series have alarmingly reported rates up to 10%, and even 29% with prior exposure to fludarabine [6,7,8,9]. However, most studies evaluating the excess risk of t-MN after IbT relative to other treatment options were limited by small sample sizes and low power [7, 8]. Despite years of use in clinical practice, the incidence of t-MN after IbT, and association with exposure to prior chemotherapy, remain unexplored in the real-world setting. Furthermore, indolent B-cell lymphomas treated with IbT occur largely among older patients who are under-represented in clinical trials. Such patients experience significant competing mortality, as well as inherent risk of myeloid disorders, which may impact their risk of t-MN. Our objective was to use population-based data to examine real-life application of IbT, and associated incidence of t-MN among older patients with B-cell lymphomas.

Among 43,945 beneficiaries (median age of 76 years, Table 1), 428 (1.0%) received IbT, at median 18 months from first-line chemotherapy (interquartile range [IQR], 8–34). IbT was used most frequently in follicular (50.0%) and diffuse large B-cell lymphoma (22.7%) and was applied as first-line treatment in 40 patients (9.3%). Median overall survival after IbT administration varied by lymphoma histology (1.0 years for diffuse large B-cell, 1.6 years for mantle cell, 3.2 years for follicular, and 4.1 years for marginal zone lymphoma; Supplemental Fig. S1) and setting of IbT use (4.1 years for first line and 2.5 years for subsequent line of therapy; Supplemental Fig. S2).

Table 1 Characteristics of Medicare beneficiaries with B-cell lymphoma according to receipt of ibritumomab tiuxetans.
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Fig. 1: Analysis of secondary t-MN among Medicare beneficiaries receiving IbT for treatment of B-cell lymphomas.

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Acknowledgements

This study used the linked SEER-Medicare database. The interpretation and reporting of these data are the sole responsibility of the authors. We acknowledge the efforts of the National Cancer Institute; the Office of Research, Development and Information, CMS; Information Management Services (IMS), Inc.; and the Surveillance, Epidemiology, and End Results (SEER) Program tumor registries in the creation of the SEER-Medicare database. The collection of cancer incidence data used in this study was supported by the California Department of Public Health as part of the statewide cancer reporting program mandated by California Health and Safety Code Section 103885; the National Cancer Institute’s Surveillance, Epidemiology and End Results Program under contract HHSN261201000140C awarded to the Cancer Prevention Institute of California, contract HHSN261201000035C awarded to the University of Southern California, and contract HHSN261201000034C awarded to the Public Health Institute; and the Centers for Disease Control and Prevention’s National Program of Cancer Registries, under agreement # U58DP003862-01 awarded to the California Department of Public Health. The ideas and opinions expressed herein are those of the author(s) and endorsement by the State of California Department of Public Health, the National Cancer Institute, and the Centers for Disease Control and Prevention or their Contractors and Subcontractors is not intended nor should be inferred. We acknowledge the efforts of the National Cancer Institute; the Office of Research, Development and Information, CMS; Information Management Services (IMS), Inc.; and the Surveillance, Epidemiology, and End Results (SEER) Program tumor registries in the creation of the SEER-Medicare database.

Funding

Supported by the American Cancer Society Grant (grant number 128608-RSGI-15-211-01-CPHPS) and the National Institute of General Medical Sciences (grant number U54GM115677).

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Authors and Affiliations

  1. Department of Medicine, Rhode Island Hospital, Providence, RI, USA

    Mengyang Di

  2. The Warren Alpert Medical School of Brown University, Providence, RI, USA

    Mengyang Di, Thomas A. Ollila & Adam J. Olszewski

  3. Division of Hematology-Oncology, Rhode Island Hospital, Providence, RI, USA

    Thomas A. Ollila & Adam J. Olszewski

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Contributions

M.D. designed research, conducted data analyses, interpreted data, and wrote the manuscript; T.A.O. designed research, interpreted data, and wrote the manuscript; A.J.O. curated the data, designed research, conducted data analyses, interpreted data, and wrote the manuscript.

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Correspondence to Adam J. Olszewski.

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A.J.O. reports research funding from Genentech, TG Therapeutics, Spectrum Pharmaceuticals, and Adaptive Biotechnologies. M.D. and T.A.O. declare no conflict of interest.

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Di, M., Ollila, T.A. & Olszewski, A.J. 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 (2020). https://doi.org/10.1038/s41375-020-0798-9

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