Hyperleukocytosis increases risk of fatal hyperkalemia with new ibrutinib/venetoclax regimen for refractory mantle cell lymphoma

J Chemother. 2019 Nov-Dec;31(7-8):428-431. doi: 10.1080/1120009X.2019.1687995. Epub 2019 Nov 18.

Abstract

Background: A recent phase 2 study reported success using combination of ibrutinib and venetoclax for relapsed/refractory mantle cell lymphoma (MCL). We report a case of MCL with hyperleukocytosis that developed fatal hyperkalemia after a single low initiation dose of venetoclax.Case report: A 72-year-old man with known MCL was admitted for hyperkalemia and anemia (Hgb = 6.6 g/dL, K+ =9.6 mmol/L). Repeated K+ measurements and clinical evaluation were consistent with pseudohyperkalemia. The patient's lymphocyte count had risen from 15.2 to 466.8 K/uL in the preceding 1.5 months despite 8 cycles of ibrutinib. Based on the results of a recent phase 2 study Venetoclax was added; after a single very low initiation dose of venetoclax the patient developed fatal hyperkalemia.Discussion: The proliferation of new therapies is making difficult to perform randomized clinical trials large enough to capture potential risks of new therapies in specific scenarios. Fatal hyperkalemia resulted from use of a recently recommended combination regimen for refractory/relapsed MCL in a phase 2 study, despite dose escalation and TLS prophylaxis suggesting increased risk of this regimen for patients with hyperleukocytosis.

Keywords: Lymphoma; adverse drug event; ibrutinib; leukocytosis; mantle-cell; venetoclax.

Publication types

  • Case Reports

MeSH terms

  • Adenine / analogs & derivatives
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bridged Bicyclo Compounds, Heterocyclic / adverse effects
  • Bridged Bicyclo Compounds, Heterocyclic / therapeutic use*
  • Humans
  • Hyperkalemia / chemically induced*
  • Leukocytosis / physiopathology*
  • Lymphoma, Mantle-Cell / drug therapy*
  • Male
  • Neoplasm Recurrence, Local / drug therapy
  • Piperidines
  • Pyrazoles / adverse effects
  • Pyrazoles / therapeutic use*
  • Pyrimidines / adverse effects
  • Pyrimidines / therapeutic use*
  • Sulfonamides / adverse effects
  • Sulfonamides / therapeutic use*

Substances

  • Bridged Bicyclo Compounds, Heterocyclic
  • Piperidines
  • Pyrazoles
  • Pyrimidines
  • Sulfonamides
  • ibrutinib
  • Adenine
  • venetoclax