ASH 2023 | Five-year follow-up of the CAPTIVATE trial: ibrutinib retreatment in patients with CLL

We are presenting at ASH in San Diego the update after five years of follow-up of the CAPTIVATE study. The CAPTIVATE study is a Phase II international study, where patients with chronic lymphocytic leukemia in frontline have been treated with the combination of ibrutinib, given for three months as a lead-in and then combined with venetoclax for 12 months. The study was made of two different cohorts. One cohort was MRD driven, so patients at the end of the treatment were randomized based on the level of MRD or minimal residual disease achieved. And then we had a cohort of fixed duration. And indeed the fixed duration treatment is what has been approved in the European Community and can be used now in frontline for patients.

Now we are presenting the follow-up. In particular, we are presenting the data on the retreatment of patient progressing after the combination of ibrutinib plus venetoclax. So we combine part of the two cohorts of patients. So all those patients who stopped the treatment, either because it was in the pre-fixed, predetermined, cohort where everybody stopped at the end of the 15 months, or in the MRD cohort, those who stopped because they reached undetectable MRD. So we combine all these patients and actually very few of these patients, only 53 patients progressed and four of them had a Richter transformation. All the others progressed with the CLL and they had the possibility to be retreated. I have to say that roughly two-thirds of the patients have not yet needed the retreatment. The other patients had been retreated mainly with ibrutinib continuous treatment and, a small portion, six patients with ibrutinib plus venetoclax. Seven patients have been treated with other treatments.

The interesting point that I think is what is the major conclusion of this work is that patients who relapsed after ibrutinib plus venetoclax can be safely and effectively treated either with ibrutinib alone or venetoclax plus ibrutinib if more than two years after the end of the treatment. And in fact, virtually all patients responded. And those patients that I presented who did not officially respond is because the follow-up was too short. But with the longer follow-up, we indeed saw that the patients achieved either partial response or complete response. So that’s very reassuring. And the other message, which is also important, is that this patient did not develop mutations in BTK or BCL2. So that again suggested that patients remain responsive to these drugs, as shown also by the efficacy of the retreatment.