PI3K Inhibitors in R/R Follicular Lymphoma - Episode 1

Historic Perspective on the Treatment of FL

January 7, 2019

Pier Luigi Zinzani, MD, PhD:Right now, the frontline of follicular lymphoma, of course, is represented by bendamustine plus rituximab, or CHOP [cyclophosphamide, doxorubicin, vincristine, and prednisone] plus rituximab, or CVP [cyclophosphamide, vincristine, and prednisone] plus rituximab. Regarding the relapsed and refractory patients, there are a few classes of drugs—for example, PI3K inhibitors. The first one was idelalisib. Then there is a new one with official indication by FDA; it’s called copanlisib. And this is a very interesting drug when you compare [it] with idelalisib because in terms of clinical response, according to the CHRONOS-1 trial, where I was involved — on which I put several patients — the overall response rate is 65%, and the CR rate is 14%, according to the best overall response rate, the best CR rate. If you compare that with the data of idelalisib, they are the same. But if you compare the safety profile of both drugs, there is a real huge difference in terms of extra toxicity. In particular for idelalisib, you can observe in at least 10%, 15% of patients diarrhea grades 3 and 4, also colitis infection and pneumonitis. This could be a real problem for several patients because they have to discontinue the treatment.

On the other hand, with the new PI3K inhibitor, copanlisib, there is a different safety profile. There is a drastic reduction of pneumonitis infection, colitis, and also diarrhea. At the same time, there is a specific extra toxicity represented by hypertension and by hyperglycemia. This is not a real problem when you compare the bad diarrhea, in terms of [grades] 3 and 4 pneumonitis, because you can control very well hypertension and, at the same time, the hyperglycemia. And also, these 2 extra toxicities are present in just the first 4, 6, no more than 8 weeks. And anyway, you can control them very well during the treatment. In terms of clinical response, there is no difference when you compare copanlisib and idelalisib in terms of overall response rate in terms of CR rate. This is very important. So you have the same results but, at the same time, a really different safety profile for your patient with relapsed or refractory follicular lymphoma.

Transcript edited for clarity.