title: Tumor lysis syndrome in the era of novel and targeted agents in patients with hematologic malignancies: a systematic review.
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.
authors.affiliation: University of Memphis, School of Health Studies, Memphis, TN, 38002, USA. Scott.howard@worldchildcancer.us.
authors.forename: Scott C
authors.initials: SC
authors.lastname: Howard
authors.affiliation: Northwestern Memorial Hospital, Chicago, IL, USA.
authors.forename: Steven
authors.initials: S
authors.lastname: Trifilio
authors.affiliation: Colorado Blood Cancer Institute at Presbyterian St. Luke's Medical Center, Denver, CO, USA.
authors.forename: Tara K
authors.initials: TK
authors.lastname: Gregory
authors.affiliation: University of Arkansas for Medical Sciences, Myeloma Institute, Little Rock, AR, USA.
authors.forename: Nadine
authors.initials: N
authors.lastname: Baxter
authors.affiliation: The University of Arizona Cancer Center, Tucson, AZ, USA.
authors.forename: Ali
authors.initials: A
authors.lastname: McBride
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects*; D002986:Clinical Trials as Topic / Q000379:methods; D016503:Drug Delivery Systems / Q000009:adverse effects / Q000379:methods*; D019337:Hematologic Neoplasms / Q000175:diagnosis* / Q000188:drug therapy*; D006801:Humans; D012307:Risk Factors; D015275:Tumor Lysis Syndrome / Q000175:diagnosis* / Q000209:etiology
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents
keywords: Hematologic malignancies; Prophylaxis; Targeted treatment; Tumor lysis syndrome