Blood cancers

Australian study provides insight into long-term efficacy of venetoclax in relapsed CLL

An extended follow-up on pooled data from four early-phase clinical trials of venetoclax in patients with previously treated CLL or small lymphocytic lymphoma has confirmed which patients are most likely to do well.

The study, comprising 436 patients who had been heavily treated with a median of three prior therapies, found a three-year progression free survival of 83% in patients who had achieved complete remission (CR) on venetoclax.

The majority of patients had one of more characteristics associated with poor prognosis such as del(17p), del(11q) or bulky adenopathy ≥5cm at study entry.

Median follow-up on the patients was 35.5 months (range 0-69 months).

Lead author Professor Andrew Roberts, from the Walter and Eliza Hall Institute of Medical Research (WEHI), Melbourne, told the limbic patients who achieved CR or MRD negativity in the blood did very well in the long term.

“The bottom line is that the majority of people have responded well to venetoclax but the people who have the greatest reduction in the amount of leukaemia, do best in the long run.”

The study found patients who had more than three prior therapies or prior ibrutinib therapy had a lower chance of any response or complete remission while patients with bulky disease were also less likely to achieve complete remission.

“One of the things you can certainly do if people have bulky disease is make sure you add in another drug. Here in Australia, under PBS, venetoclax is approved for treatment of relapsed CLL in combination with rituximab.”

He said while the combination doesn’t fully overcome the negative prognostic features associated with bulky disease, it did make a difference.

“The aim of treatment with venetoclax or venetoclax plus rituximab should be to get a CR or at least MRD negative and if so, patients are destined to do well in the long term.”

“But even with that, if you start with bulky disease or have an aberration of p53 gene or have a mutation in NOTCH 1 or previously failed the BTK inhibitor ibrutinib, then their remission and response isn’t going to be as a long as someone who either didn’t have those features or didn’t have the previous treatment.”

He said an extended follow-up focused on safety had found the drug was fairly well tolerated with most people having some side effects, commonly nausea or loose bowels.

“Importantly the risk of tumor lysis syndrome is very low if you follow the rules and give it slowly. And we found the risk of infection in CLL was also quite low.”

Professor Roberts added there was a lot of interest in the soon-to-be-released findings from the first trial of venetoclax plus obinutuzumab versus standard chemotherapy plus obinutuzumab in the first line setting.

Disclosure: WEHI receives royalties related to venetoclax and Professor Roberts also receives a financial benefit as a result of previous work developing venetoclax. The research was funded by Abbvie.

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