ASH 2021 | CAPTIVATE: Ibrutinib and venetoclax in CLL
Jacqueline Barrientos, MD, MS, Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, shares data from the Phase II CAPTIVATE trial (NCT02910583), which investigated the Bruton’s tyrosine kinase (BTK) inhibitor ibrutinib and venetoclax in patients with chronic lymphocytic leukemia (CLL). Patients initially received ibrutinib as debulking therapy, and then received 12 cycles of ibrutinib with venetoclax. Complete remission and minimal residual disease (MRD) were observed in a large number of patients, with no changed in toxicity reported. Ibrutinib with venetoclax is a promising regimen that is effective in patient with CLL and can additionally reduce progression rates in patients. This interview took place at the 63rd ASH Annual Meeting and Exposition congress in Atlanta, GA.
Transcript (edited for clarity)
So the CAPTIVATE study is a Phase II study in treatment-naive patients with a diagnosis of CLL. It included even patients that had a 17p deletion, and it combined ibrutinib, a first generation BTK inhibitor, with the BCL-2 inhibitor, venetoclax. The way that the trial was designed was to do an initial debulking phase of three months of ibrutinib. And then that minimizes the risk for tumor lysis syndrome, which is a known, bad outcome that can happen in patients that are treated with venetoclax when they start...
So the CAPTIVATE study is a Phase II study in treatment-naive patients with a diagnosis of CLL. It included even patients that had a 17p deletion, and it combined ibrutinib, a first generation BTK inhibitor, with the BCL-2 inhibitor, venetoclax. The way that the trial was designed was to do an initial debulking phase of three months of ibrutinib. And then that minimizes the risk for tumor lysis syndrome, which is a known, bad outcome that can happen in patients that are treated with venetoclax when they start. Then we start off the ramp up schema per guidelines, which is 20 milligrams per week, and then followed by 50 milligrams, a hundred milligrams, 200 milligrams to target dosing of 400 milligrams. Once you get to the 400 milligram dose, you combine both ibrutinib continue and 400 milligrams daily of venetoclax for a total of 12 cycles. So a total of 15 cycles in total for a patient is three months of ibrutinib and then combined therapy of 12 months.
And then you stop. And what you do is you see what happens with these patients after the fixed duration treatment strategy. And what we found out was that there were a very high number of majority of patients who achieved complete remission and undetectable MRD, and they are still in remission even two years later off any therapy. There was no increase in the toxicity profile of the combination of the study in patients that are young and fit. Very few discontinuations, very few drug holds. And so for us, I think it’s a very promising new regimen. And in the future, it might allow us to stop either drug in a sense that we can then minimize the potential for toxicities that can occur later on. And it can also minimize the risk for mutations that stop the response. Like for example, minimize the risk for progression due to a BTK mutation, PLC gamma mutation or BCL-2 mutation. So it’s a very promising new treatment strategy that is currently being evaluated, not only under the CAPTIVATE study, in several other study centers as well.
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