Ibrutinib and venetoclax continue to provide benefits for patients with chronic CLL and SLL

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Published: 24 Jun 2024
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Dr Paolo Ghia - Università Vita-Salute San Raffaele, Milan, Italy

Dr Paolo Ghia talks to ecancer about the phase 2 CAPTIVATE study.

It demonstrated that first-line treatment with ibrutinib and venetoclax in CLL/SLL patients provided a 5-year progression-free survival rate of 67% and overall survival rate of 96%.

Higher progression-free survival was seen in patients with undetectable minimal residual disease.

Patients with high-risk genomic features had varied progression-free survival rates, with 41% for those with del(17p)/mutated TP53.

Retreatment with ibrutinib alone or with venetoclax showed promising response rates (86% and 71%, respectively).

The combination therapy offers durable benefits, especially for high-risk patients.

Ibrutinib and venetoclax continue to provide benefits for patients with chronic CLL and SLL

Dr Paolo Ghia - Università Vita-Salute San Raffaele, Milan, Italy

The study is the CAPTIVATE study which is a phase II international multicentre study where we explored the combination of ibrutinib, a BTK inhibitor, with venetoclax, a BCL-2 inhibitor, as front-line therapy in patients with chronic lymphocytic leukaemia.

What was the study design?

The study design was a little bit complicated, it consisted of two different cohorts. They were not randomised, they were different cohorts. The first cohort was the so-called MRD, minimal residual disease, cohort where patients were treated with three months of ibrutinib and then 12 months of the combination of ibrutinib plus venetoclax and then at the end of the 15 months of treatment patients were randomised based on the level of undetectable MRD. Patients who reached undetectable MRD were randomised to either placebo, so to stop the treatment, or to continue ibrutinib, while instead the patients who did not achieve undetectable MRD were randomised to continue either ibrutinib as a continuous therapy or ibrutinib plus venetoclax.

The other cohort was the so-called fixed duration cohort where patients at the end of the 15 months all interrupted the treatment, regardless of MRD status.

What were the results of this study?

The results of the study, here at EHA we presented the results, an update of the results of the patients who stopped the treatment to see actually how the patients would perform as a long-term outcome in a fixed duration manner of treatment but also to see how the patients could be re-treated when relapsing.

In this study that we presented we have now a median follow-up of 5.5 years and what we showed is that the responses were very durable. Roughly three-quarters of the patients still maintained a response after a median of 5.5 years and there were differences, as we know, based on the genetic features of the patient. In particular, the unmutated patients, patients with unmutated immunoglobin genes that are considered to be the most difficult to treat, they still also maintained a response that was present in 68% of the patients after 5.5 years.

Patients with aberration of the p53 gene which are the very high risk patients had a progression earlier but still roughly around 50% of the patients were still in response after 5 years of treatment. So, overall every patient benefitted from that. What was more interesting is that those patients who relapsed could be re-treated with either ibrutinib alone or ibrutinib plus venetoclax, achieving responses in most of the cases.

What is the clinical significance of these results?

The results are clinically very relevant because we show that we can provide a fixed duration treatment that is very simple to administer because it’s all oral. Virtually all patients, including those with high risk features can benefit from it in terms of progression free survival and durability of response. In addition, we can also show that patients can be re-treated using the same drugs so we are not losing any options for our patients but all options remain on the table when they need again treatment.

What is next for this study?

It’s a longer follow-up, that’s always what we want to see because we want to be reassured on the length and durability of the responses and we want also to increase the number of patients who will eventually need treatment. So really to have again consistent results in terms of re-treatment.