Blood cancers

Synergy in new drug combo for lymphoma

Australian research has found the new combination of ibrutinib and venetoclax is effective in patients with relapsed or refractory mantle cell lymphoma.

The phase 2 study, presented recently at the 14th International Conference on Malignant Lymphoma in Lugano, Switzerland, is the first in the world to report on patients receiving full clinical doses of the two drugs.

Associate Professor Con Tam, director of haematology at St Vincent’s Hospital Melbourne and lead for low-grade lymphoma at the Victorian Comprehensive Cancer Center, told the limbic ibrutinib alone had resulted in a complete remission rate of 9% at the same assessment timepoint in a similar group of patients.

“We are now seeing a complete remission rate of 58% at week 16 which in our view is demonstrating a synergistic effect. In addition, 77% of complete responders are negative for minimal residual disease as evaluated by marrow flow cytometry.”

The study of 24 patients, mostly men with a median age of 68 years, started patients on ibrutinib then introduced a standard ramp-up of venetoclax to 400mg daily.

“Our number one concern was massive tumour lysis syndrome. However in most patients ibrutinib was very helpful in reducing tumour bulk which lessened the risk of tumour lysis syndrome.”

He said they were not surprised when the two patients who did not respond to ibrutinib, and instead had tumour growth during ibrutinib induction, developed features of tumour lysis syndrome on venetoclax initiation. These patients had bulky disease at the time of venetoclax dosing.

Although both patients could be managed and both dose escalated to 400mg venetoclax, neither did well overall.

Associate Professor Tam said there was more work to be done to identify the biomarkers that could help predict response to the combination of drugs.

“There were no obvious clinical features to predict who was going to respond or not. All patients had highly refractory disease and had failed previous chemotherapy or a stem cell transplant.”

A phase 3 study and similar research in CLL and marginal zone lymphoma were underway.


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