ASH 2021 | 2 year DFS data from the CAPTIVATE trial

The CAPTIVATE Study is an international, multicenter, Phase II study evaluating patients with chronic lymphocytic leukemia in first line treatment. And the cohort, there are two different cohorts, a so-called fixed duration cohort and the MRD, minimal residual disease cohort. The results of this cohort, I presented at ASH this year.

In this case, the patients were treated for three months with ibrutinib as debulking agent, and then for 12 cycles, 12 months with a combination of ibrutinib plus venetoclax. At the end of the 12 months of combination, patients were randomized based on the level of MRD or minimal residual disease achieved. Those who achieved undetectable MRD, they were randomized to either stop the treatment, so a placebo arm, or continue ibrutinib monotherapy. The patients who did not achieve undetectable MRD, they were randomized to continue either ibrutinib monotherapy, or ibrutinib plus venetoclax.

And this year I presented at ASH two-year disease-free survival, and the disease-free survival is different from the progression-free survival, because it considers not only freedom from progression of disease and death, but also freedom from MRD relapse. So it is much more stringent than the PFS rate.

In this case, we showed the two-year disease-free survival of the placebo and ibrutinib arm and here they are both more than 95% with no significant difference so suggesting the idea that patients with confirmed undetectable MRD can safely interrupt the treatment as there is no difference with continuing ibrutinib.

We also presented the three-year progression-free survival for all the arms of the study. So for the placebo and the ibrutinib arm, for patients who achieved undetectable MRD, but also for the ibrutinib and ibrutinib plus venetoclax arm for the patients who did not achieve undetectable MRD. And all together, the three-year PFS rate is more than 95% in all the four arms indicating that if we tailor the treatment based on the level of MRD, we can optimize the outcome for all the responses in all our patients.

We achieved these amazing results, I would say, with a very safe toxicity profile. So the combination of ibrutinib plus venetoclax did not show any increase in terms of adverse events, with the exception of diarrhea that was present in more than 50% of the patients, but in most of them, if not all, of low grade.

On the other side, patients experienced adverse events in similar frequencies expected from the monotherapy. So like for example, 35% of patients experienced neutropenia likely due to mostly due venetoclax, but this did not translate into an increase of infection that was only present in 8% of the patient. Also, very low frequency of atrial fibrillation and major hemorrhage that are typical adverse events associated with ibrutinib.