Clear role for kinase inhibitors in CLL, says expert

Blood cancers

By Mardi Chapman

29 Nov 2016

Patients with relapsed/refractory chronic lymphocytic leukaemia (CLL) who have to discontinue use of a kinase inhibitor can be salvaged by switching to an alternate drug in the same class.

According to a retrospective US study of 178 CLL patients who discontinued either ibrutinib or idelalisib, the sequence of kinase inhibitors for those who switched did not affect progression free survival or overall survival.

The overall response rate to a first kinase inhibitor was 62% and 50% for the subsequent drug.

Professor Stephen Mulligan, senior staff specialist at the Royal North Shore Hospital and president of the CLL Australian Research Consortium, said kinase inhibitors had a clear role in the relapsed/refractory setting and an increasing role as frontline therapy.

“These agents are life saving. They meet a previously unmet need and revolutionise our management – keeping patients alive who would otherwise have succumbed to their disease.”

“There has been widespread adoption of ibrutinib in particular which is generally well tolerated and remarkably effective but the information has been relatively slow in coming in,” he said.

He said ibrutinib was currently under consideration by the PBAC and expected to be available on the PBS in early 2017.

The 50% response rate to a second kinase inhibitor was evidence that we need access to more than one of these agents, he added.

The study found about half (51%) of patients discontinued kinase inhibitor therapy because of adverse effects including atrial fibrillation, infection or cytopenias with ibrutinib and pneumonitis, colitis or rash with idelalisib.

However Professor Mulligan said the rate of discontinuation due to adverse effects was far in excess of his clinical experience with the drugs.

He said multiple complex interactions between patients’ haematological needs, bleeding risks due to platelet inhibition and AF-induced stroke risk requiring anticoagulation could be managed without discontinuation of the drug.

 The study found other reasons for discontinuing the drugs included CLL progression (29%) and Richter transformation (8%). Alternate kinase inhibitor therapy in these cases were however associated with poorer outcomes.

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