Ibrutinib plus venetoclax for the first-line treatment of CLL/SLL: Results from the CAPTIVATE study
Prof Constantine Tam - Peter MacCallum Cancer Centre, Melbourne, Australia
The CAPTIVATE study is a frontline study in CLL and it’s a study of a combination of ibrutinib plus venetoclax for the frontline treatment of CLL. By way of background, up to this time most of the data surrounding CLL has been with chemotherapy and more recently with the BTK inhibitor studies. BTK inhibitors have become a standard of care in frontline but need to be continued indefinitely.
So CAPTIVATE asked the question of whether combining ibrutinib and venetoclax, so two oral novel agents, may be able to give us a time-limited treatment option where patients can take the therapy for a period of time and then come off therapy in deep remission. In short, 164 patients were enrolled. The patients received three months of ibrutinib followed by twelve months of ibrutinib combined with venetoclax.
What we found was that the regimen was very well tolerated. It was an entirely oral regimen. Patients had a less than 5% discontinuation rate due to adverse events and 90% of patients were able to complete the treatment sequence. After the twelve months of combination therapy patients had very deep responses and, in fact, the minimal residual disease clearance rate in those patients was 75% meaning that three out of four patients were able to achieve the deepest remission possible using an all-oral novel therapy induction regimen.
Those are very encouraging results. At the moment there are different cohorts enrolled in this study. Some patients are assigned to have ongoing therapy, others are assigned to stop all the treatment altogether. So time will tell whether this very deep remission is durable without any requirement for maintenance treatment and whether this is a viable option as a time-limited treatment.
152 patients completed the treatment sequence in this cohort and were assigned to different maintenance strategies including no treatment, treatment with ibrutinib alone or treatment with the combination indefinitely. Because of the high disease clearance rate seen in this cohort we have also recruited a separate cohort of patients and there are 159 patients. Those patients simply received the twelve months of combination therapy and then they stopped. That cohort is about one year behind because the data is less mature but by the time we’ve finished we will have around 350 patients assigned to different strategies and we can define what the best post-induction strategies are.
Really we aren’t seeing any unusual side effects above the expected of ibrutinib and venetoclax individually. Probably for us some of the major concerns are tumour lysis syndrome, which is a big issue with venetoclax. But what we have found was that after three months of ibrutinib that almost all the patients who were at high tumour lysis risk have decreased to intermediate or low tumour lysis risk because the ibrutinib has managed to debulk the disease. So in the first cohort of 164 patients only one patient developed tumour lysis syndrome and this was a laboratory only event with no clinical consequence.
What this means for the patients is that instead of looking at chemotherapy or indefinite novel therapy that there is now on the horizon very soon a combination of novel therapies that will allow them to take treatment for a fixed duration of time and come off treatment in very good remission and be able to live hopefully normal, treatment-free lives for several years.