Safety and efficacy of the novel BTK inhibitor zanubrutinib in patients with CLL/SLL

Prof Constantine Tam - Peter MacCallum Cancer Centre, Melbourne, Australia

Both of my other oral presentations concern the new BTK inhibitor zanubrutinib. This is a second generation BTK inhibitor. It’s different from ibrutinib in that it’s more specific so potentially there will be less side effects. Also the drug is very potent and very high drug levels; the drug levels are about eight times higher than that of ibrutinib. What we reported are two cohorts of patients. We reported a cohort of patients with CLL that we treated for about 2½ years on this drug and these are patients from the original phase I study of zanubrutinib. What we reported was a very favourable safety profile so the drug behaved like ibrutinib in terms of side effects. So you still get bruising and atrial fibrillation and the ibrutinib side effects but the rates are numerically lower. So, for example, atrial fibrillation which happens in about 5-10% of patients treated on ibrutinib is under 5% with this drug. The drug is very effective, we had high response rates and the remission durations are durable.

Based on the initial phase I study we have gone on to do a registration phase III study which is the subject of my second presentation. In that phase III study patients are randomised between zanubrutinib and chemotherapy as first line treatment of CLL. However, if during screening they are identified to have a 17p deletion on FISH which predicts chemoresistance, those patients are not randomised and are assigned to receive zanubrutinib alone.

So my second presentation is actually not about the randomised portion of that study, it’s about those patients who have got 17p deletion CLL who traditionally do very poorly with normal treatment and how they went when they were assigned to zanubrutinib. In total we had 109 patients treated with zanubrutinib for 17p deletion CLL and we had a very high response rate – 92.7%. There was only one patient who progressed, who had primary progression. So basically everyone responded to the drug and at about ten months of follow-up, so a fairly short follow-up so far, but the remissions appear to be very durable.

I don’t think the data is surprising. We knew that BTK inhibitors as a class work well for 17p deletion CLL. But it’s very gratifying to see a high response rate, durable responses, the toxicity profile was very benign and also this is possibly the largest experience with 17p CLL treated uniformly in the front line. So we look forward to updating this cohort in subsequent meetings.