Ibrutinib plus venetoclax is a trial we designed a few years ago. Ibrutinib is currently approved for patients with CLL and venetoclax is also approved for patients with relapsed refractory CLL. So a few years ago, based on some level 3 data and some other convincing data we felt that these drugs personally could be safely combined and they might lead to increased activity, clinical activity, of these drugs.
So we designed this clinical trial where patients get three months of ibrutinib first and then we add venetoclax and continue the ibrutinib for a total of two years. We reported the data for the first 80 patients we have treated with the first line therapy of CLL and these were the patients who had high risk features such as deletion 17p, deletion 11q, unmutated V gene, and those are the data we reported at the ASH meeting a couple of days ago.
What we saw was that at one year of the combination 61% of the patients had undetectable MRD, so there was no MRD detectable, and approximately close to 90% of the patients had achieved a complete remission. So these rates appear to be much higher than what you would have achieved if you had used these drugs by themselves. So by combining the drugs we are seeing much higher efficacy. I should point out that one of the side effects we are seeing more is called neutropenia and we are seeing more of that, almost 50% of the patients had what is called grade 3 or 4 neutropenia. But that was easily manageable by halting the drugs, decreasing the dose of the drugs or using growth factor support such as GCSF.
What could be the implications?
This is a concept which is now emerging quite a bit in the field; it’s not just us there are other groups also looking at the same combination, also for frontline patients as well as for relapsed refractory patients. The early data seems to be consistent in all the studies that this combination is quite active for patients – high rates of remissions are achieved for the patients. So there are already randomised phase III studies ongoing where this combination is being tested so depending on the results of those studies, which may take a couple of years or three years down the line, we’ll have to see if these studies are positive but if they are positive then this may eventually become maybe one of the potential regimens to treat patients with CLL.
One of the advantages of this regimen is that it’s a one or two year regimen, depending on the study you look at. That’s an advantage because if you were to take ibrutinib by itself you will take the drug forever, for the rest of your life, that’s the recommendation. So basically by giving one or two years of therapy, a time-limited approach, you’re able to cut down the cost of the drugs, you’re able to cut down possibly the long-term toxicities of the drug so that would be also an appealing aspect of it. But, again, I should point out that all the studies we are doing and others are doing are right now early on. Most of the studies have been enrolling in the last one or two years so we will have to wait some more time before we see how these responses are met.