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Tumor lysis syndrome in the era of novel and targeted agents in patients with hematologic malignancies: a systematic review

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Abstract

Effective new treatments are now available for patients with hematologic malignancies. However, their propensity to cause tumor lysis syndrome (TLS) has not been systematically examined. A literature search identified published Phase I–III clinical trials of monoclonal antibodies (otlertuzumab, brentuximab, obinutuzumab, ibritumomab, ofatumumab); tyrosine kinase inhibitors (alvocidib [flavopiridol], dinaciclib, ibrutinib, nilotinib, dasatinib, idelalisib, venetoclax [ABT-199]); proteasome inhibitors (oprozomib, carfilzomib); chimeric antigen receptor (CAR) T cells; and the proapoptotic agent lenalidomide. Abstracts from major congresses were also reviewed. Idelalisib and ofatumumab had no reported TLS. TLS incidence was ≤5 % with brentuximab vedotin (for anaplastic large-cell lymphoma), carfilzomib and lenalidomide (for multiple myeloma), dasatinib (for acute lymphoblastic leukemia), and oprozomib (for various hematologic malignancies). TLS incidences were 8.3 and 8.9 % in two trials of venetoclax (for chronic lymphocytic leukemia [CLL]) and 10 % in trials of CAR T cells (for B-cell malignancies) and obinutuzumab (for non-Hodgkin lymphoma). TLS rates of 15 % with dinaciclib and 42 and 53 % with alvocidib (with sequential cytarabine and mitoxantrone) were seen in trials of acute leukemias. TLS mitigation was employed routinely in clinical trials of alvocidib and lenalidomide. However, TLS mitigation strategies were not mentioned or stated only in general terms for many studies of other agents. The risk of TLS persists in the current era of novel and targeted therapy for hematologic malignancies and was seen to some extent with most agents. Our findings underscore the importance of continued awareness, risk assessment, and prevention to reduce this serious potential complication of effective anticancer therapy.

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Acknowledgments

Editorial and medical writing support was provided by Laurie Orloski, PharmD, and Mariana Ovnic, PhD, at Complete Publication Solutions, LLC. This support was provided by Sanofi.

Funding

This work was supported by Sanofi.

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Authors and Affiliations

  1. University of Memphis, School of Health Studies, Memphis, TN, 38002, USA

    Scott C. Howard

  2. Northwestern Memorial Hospital, Chicago, IL, USA

    Steven Trifilio

  3. Colorado Blood Cancer Institute at Presbyterian St. Luke’s Medical Center, Denver, CO, USA

    Tara K. Gregory

  4. University of Arkansas for Medical Sciences, Myeloma Institute, Little Rock, AR, USA

    Nadine Baxter

  5. The University of Arizona Cancer Center, Tucson, AZ, USA

    Ali McBride

Authors
  1. Scott C. Howard
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  2. Steven Trifilio
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  3. Tara K. Gregory
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  4. Nadine Baxter
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  5. Ali McBride
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Corresponding author

Correspondence to Scott C. Howard.

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Conflict of Interest

SH has served as a consultant and/or speaker for Sanofi, Jazz Pharmaceuticals, and Sigma Tau and received research funding from Jazz Pharmaceuticals and BTG. ST has served as an advisor to Sanofi. TKG has served as a consultant to Novartis, Celgene, and Sanofi. NB has served as an advisor and speaker for Sanofi. AM has served as an advisor for Sanofi.

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Howard, S.C., Trifilio, S., Gregory, T.K. et al. Tumor lysis syndrome in the era of novel and targeted agents in patients with hematologic malignancies: a systematic review. Ann Hematol 95, 563–573 (2016). https://doi.org/10.1007/s00277-015-2585-7

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  • DOI: https://doi.org/10.1007/s00277-015-2585-7

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