The stem of our question is from seeing patients in clinic who, unfortunately, have progression of their disease following a CD19 specific CAR T-cell therapy for large B-cell lymphomas. Currently there is not a lot of data to guide us in terms of how to best manage these individuals. So what our group data at the University of Washington and Fred Hutchinson Cancer Research Center, what we did was look at a cohort of patients that, unfortunately, showed progression of disease and we tried to delineate their outcomes and look at different predictors of outcomes.
How did you do this?
We identified almost 60 patients and, unfortunately, they were individuals that progressed either early or a little bit later. How we defined these two groups were early progressors were those that essentially had evidence of disease progression really at their first restaging studies. The other group that we defined as a cohort of delayed progressors had either stable disease or better on their initial disease response assessment and subsequently progressed or had to receive any anti-lymphoma therapy.
What we found was when we combined the two groups together for our cohort of about 58 patients the median overall survival after evidence for progression was roughly 5-6 months which is not great. It’s also a little bit more discouraging in that when we separated out the two groups those that progressed early really did not do well, median overall survival around 3 months or so compared to those who had some benefit from CAR T-cell therapy and then subsequently progressed – they had a median overall survival of about 13-14 months. So certainly the early progressors, in our opinion, are a pretty high risk group and certainly much more research should be done in terms of looking at how to manage these individuals when we see them back in clinic.
What’s next?
This was really hypothesis generating, gathering some data. Probably for the first time looking specifically at patients who progressed and trying to get a better understanding, at least from our institution, of how we’re treating them. What we found was very few individuals enrolled onto a clinical trial right after evidence for progression and certainly multiple reasons are at play. Very few people ended up getting an allogeneic stem cell transplant but of the five people who eventually got a transplant, two of them are still alive so there is some suggestion that if patients are able to get subsequent therapy they will survive longer. Understanding that space right now will be critical in helping our patients.
Hopefully this is going to be data that helps generate clinical trials and prospective studies, potentially combination approaches, and really affecting durable complete responses for our patients so that they don’t even have evidence for progression after receiving the CAR T-cell therapy because it’s such a promising therapy.
