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.

Patients’ priorities in selecting chronic lymphocytic leukemia treatments

“…This overstates the actual risk, which is highest at the start of treatment. 18,19 Cost had a big impact on treatment choice.…”

Management of patients with previously untreated chronic lymphocytic leukaemia with obinutuzumab and chlorambucil

“…Patients at the highest risk of tumour lysis syndrome (TLS) are those with bulky disease or those with a very high circulating tumour burden, for example, those with white cell counts of more than 50 × 10 9 /L . TLS was observed in 14 patients (4%) treated with obinutuzumab–chlorambucil in the CLL11 study, compared to none in the rituximab–chlorambucil arm and <1% in the chlorambucil monotherapy arm.…”

The confused oncologic patient: a rational clinical approach

“…24–27 Volume depletion and hematologic cancers associated with a high tumor burden are the major risk factors. Encephalopathy and seizures are common symptoms; prevention and treatment require aggressive hydration, urine alkalinization, and allopurinol or rasburicase to reduce urate levels.…”