Venetoclax (Venclexta) in combination with obinutuzumab has been added to the PBS as a first line therapy in patients with CLL who are unfit for conventional chemotherapy.
The PBS listing follows trial data including from the CLL-14 study published last year in the NEJM which found venetoclax and obinutuzumab was associated with longer PFS than chlorambucil and obinutuzumab.
Professor Stephen Opat, from Melbourne Haematology and Monash Health, told the limbic the extended PBS listing provides a new treatment option for older patients who aren’t fit for chemotherapy due to comorbidities, particularly renal impairment.
“So the problem was, with older patients you could only give gentle chemotherapy which meant you didn’t get such a deep response which means they would relapse sooner or not even respond.”
“But with venetoclax and obinutuzumab, you can get the same sort of depth of response without the toxicity that you see with chemotherapy. So now, older patients can get the same sort of response you would see in younger patients with treatment like FCR chemotherapy.”
He said the ongoing CRISTALLO study would provide evidence for first line therapy with the novel combination in younger patients otherwise fit for chemotherapy.
“There just needs to be more time for the data to mature,” he said.
“These trials are largely showing improvement in progression free survival and we are hoping to see improvement in overall survival over time. It might take 4-5 years to see a survival difference, if it’s there.”
He said the future was probably that, as in myeloma, all patients will eventually see all the different agents: “…some patients you are going to be able to treat with venetoclax-obinutuzumab and they might never need another treatment. And others, as soon as you stop after 2-3 years, the disease will come back.”
“So I think the next step is for us to further understand the molecular profile which will work out who responds best to a fixed duration treatment and who is going to need a continuous treatment.”