ASH 2013 - New Orleans, LA, US
New agents in CLL
Dr Jacqueline Barrientos - LIJ Medical Center, New York, USA
It’s an amazing time, it’s a great time. There are a lot of new drugs coming up in the pipeline and we’re expecting hopefully that the FDA will review these favourably and we will get some new drugs available for our patients. We are getting to that point where we might consider doing chemo-free therapies which is what we all want but we will see. We still don’t know for how long we can take these drugs; we still have to study a little bit more these drugs and what combinations would be best but all the results are astonishing and unprecedented in people that essentially have not a very good outcome in the past.
For example, one new drug in the pipeline which is now approved by the FDA, it’s obinutuzumab, also known as Gazyva or previously GA101. That drug has been tried and tested in people that are frail and elderly, treatment naïve, never treated before. Beautiful results and those results will be presented at this year’s plenary session by Dr Valentine Goede and colleagues from Germany. It showed a 78% overall response rate with activity in the bone marrow. There were a lot of complete remissions, about 24%, 23% of people that had a response in the bone marrow. The drug was used in combination with chlorambucil and it showed complete superiority in comparison with Rituxan and with chlorambucil or with chlorambucil alone. So it might be one new standard of care for people with treatment naïve disease.
Now, other new drugs that are now in phase III trials include ibrutinib which is a Bruton’s tyrosine kinase inhibitor that targets the B-cell signalling receptor and the other one is idelalisib and both drugs are showing unprecedented responses both in treatment naïve patients and in relapsed refractory disease. So that’s very exciting too. Those are oral drugs so there might be a new future instead of traditional chemotherapy that targets all the cells, the good ones and the bad ones, we might be able to minimise the side effect profile.
Will you select which patients are eligible or will this be given to all patients?
At this time, for example, we have very good data for relapsed refractory disease for patients with the B-cell receptor signalling agents, particularly with ibrutinib. Dr Farooqui and colleagues are going to present in patients who are older than 65 or patients with 17p deletion that could be either treatment naïve or relapsed refractory. He’s showing 66% overall response rate with an additional 24% of patients with partial remission with lymphocytosis. It’s a hard concept to understand but both agents, ibrutinib and idelalisib, they are working in a way that we never saw before. So the guidelines for response will have to be changed in the future. In the past you needed a decrease in the size of the lymph nodes and, at the same time, you also needed a decrease in the number of lymphocytes running around in your peripheral blood. But with these two agents you take the pill, your lymph nodes shrink immediately but your white blood cell count goes up. So there are some people that don’t get to be responders yet because they still have the lymphocytosis or the lymphocytes running around in your blood. We have noted that as a monotherapy the longer that you take the drug the more responses you get because the lymphocytosis eventually resolves. But in combination you see that the lymphocytosis doesn’t last as long and it’s not as pronounced. So Dr Jan Burger will present that also at this year’s ASH where he will have more mature data on his forty patients with high risk disease where they are trying ibrutinib in combination with Rituxan. He’s showing 95% overall response rate but, again, he said a word of caution – we still don’t know if the addition of rituximab will make a better outcome in the long term or it might be just a cosmetic thing, that the lymphocytosis lasts a shorter time and s less.
Now in patients that take the ibrutinib single agent, what the NIH team saw, Dr Farooqui is the leader, he’s going to present that the patients with 17p deletion are the ones that are taking the longest to get rid of the lymphocytosis. So that group of patients, even though we are getting excellent results and excellent outcomes, overall what we’ve seen from our previous data and the data that was published in the New England Journal is that those are the patients that are at a high risk for relapse later on or maybe at risk for ibrutinib resistance which we also presented at ASCO and I think the manuscript is in preparation.
If these patients relapse, is there any other option for them?
Yes, traditionally idelalisib came into the clinical trials earlier on and there were many patients that were salvaged once they’d relapsed with ibrutinib. Now there are new drugs in the pipeline, one of them is ABT-199 and personally I’ve used such a drug in one of my patients with relapsed disease. I know that there are some other groups that have used other of the drugs in the pipelines and they have been salvaged. I know that one of the patients that relapsed with the disease, he went on to the clinical trial with CAR19 from where they re-engineered the T-cells from the patients to recognise the CD19 receptor on the surface and then the cells attacked the CLL. So yes, we do have options of care as long as the patients are willing to participate in clinical trials.
