Low incidence of tumor lysis syndrome in elderly patients with chronic lymphocytic leukemia treated with venetoclax under real-world conditions: results from the prospective observational VeRVe study

Ann Hematol. 2024 Jun;103(6):2013-2020. doi: 10.1007/s00277-024-05638-7. Epub 2024 Feb 29.

Abstract

Venetoclax is active in both frontline and relapsed/refractory settings for the treatment of chronic lymphocytic leukemia (CLL). Although the prevalence and severity of tumor lysis syndrome (TLS) are well characterized in clinical trials, laboratory and clinical TLS remain relatively unexplored in real-world clinical practice.In this prospective, real-world observational study, we aimed to determine the incidence and outcomes of TLS in patients with CLL receiving venetoclax outside a clinical trial. The study (VeRVe) was conducted in centers in Austria, Germany, and Switzerland.Two hundred and thirty-nine patients were treated according to local label with at least one dose of venetoclax. Patient demographics, baseline characteristics, and blood chemistry at baseline were documented, and descriptive statistical analyses were conducted.Seventy eight patients (33%) were treated with venetoclax monotherapy, 101 (42%) with venetoclax in combination with rituximab and 60 (25%) with venetoclax in combination with obinutuzumab. In all cases, the TLS risk mitigation strategy adhered to the ramp-up protocol. Median age was 73 years and 66% of patients were male. The majority of patients (75%) had relapsed/refractory CLL, 63/192 (32.8%) patients tested had a del(17p) and 93/134 (69.4%) patients tested had unmutated immunoglobulin heavy chain variable region gene (IGHV). Clinical TLS occurred in 5 patients (2.1%) and laboratory TLS occurred in 15 patients (6.3%). Ten patients received specific treatment, of which 6 were hospitalized. There were no deaths due to a TLS event and venetoclax was well-tolerated. Of the 5 clinical TLS events reported, none were fatal or resulted in renal failure (NCT03342144, registered on Nov 10, 2017).

Keywords: Chronic lymphocytic leukemia; Real-world evidence; Tumor lysis syndrome; Venetoclax.

Publication types

  • Observational Study
  • Multicenter Study

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Austria / epidemiology
  • Bridged Bicyclo Compounds, Heterocyclic* / administration & dosage
  • Bridged Bicyclo Compounds, Heterocyclic* / adverse effects
  • Bridged Bicyclo Compounds, Heterocyclic* / therapeutic use
  • Female
  • Germany / epidemiology
  • Humans
  • Incidence
  • Leukemia, Lymphocytic, Chronic, B-Cell* / drug therapy
  • Male
  • Middle Aged
  • Prospective Studies
  • Rituximab / administration & dosage
  • Rituximab / adverse effects
  • Rituximab / therapeutic use
  • Sulfonamides* / administration & dosage
  • Sulfonamides* / adverse effects
  • Sulfonamides* / therapeutic use
  • Tumor Lysis Syndrome* / etiology

Substances

  • venetoclax
  • Sulfonamides
  • Bridged Bicyclo Compounds, Heterocyclic
  • Antibodies, Monoclonal, Humanized
  • obinutuzumab
  • Rituximab
  • Antineoplastic Agents

Associated data

  • ClinicalTrials.gov/NCT03342144