PI3K Inhibitors in R/R Follicular Lymphoma - Episode 2

Why Do Most Patients with Follicular Lymphoma Relapse?

Pier Luigi Zinzani, MD, PhD:According to the GELF criteria, we need a tumor burden—an important tumor burden—and, in this case, we have to start with the treatment. Watch and wait is the alternative according to the GELF criteria—or, in other countries, where they’re using the BNLI [British National Lymphoma Investigation] criteria. When you have a small tumor burden, you can watch and wait with an indolent lymphoma like follicular lymphoma.

Follicular lymphoma is an indolent disease. Right now, according to the conventional chemoimmunotherapy—like, for example, bendamustine plus rituximab or R-CHOP, which is cyclophosphamide, doxorubicin, vincristine, and prednisone plus rituximab—plus 2 years of maintenance, we can cure at least a third, 35% of the patients. I mean cure because we have patients, also in our institution, in continuous complete response after more than 7, 8 years. And so these are very important data for our patients. So at least one-third of the patients can be considered cured when you apply the conventional chemoimmunotherapy plus 2 years of maintenance treatment with rituximab. Anyway, of course, this being an indolent lymphoma, the other two-thirds of the patients will relapse. And for this reason, it’s very important that in the new era in terms of this new class of PI3K inhibitors, right now we can put copanlisib and idelalisib in the third line because, according to the indication by the FDA…you can use idelalisib only in double-refractory patients or rituximab-refractory patients and also alkylating agent—containing regimen refractory patients. On the other hand, you can use copanlisib in patients that relapse or refractory with at least 2 prior regimens of chemoimmunotherapy.

There is a pharmacokinetic resistance. If I use bendamustine/rituximab in frontline and I have a relapse in the second line, it’s better that I don’t use bendamustine again. You have to move to CVP [cyclophosphamide, vincristine, and prednisone] or CHOP plus rituximab. And, in particular, for a young patient, an alternative could be the consolidation with transplantation after the salvage treatment with CHOP or CVP.

When I compare the NCCN [National Comprehensive Cancer Network] Guideline and the European Guidelines, some differences are called into the different healthcare system anyway. For the relapsed/refractory patient, you can use CHOP-R or CVP-R because right now, in…most…American hospitals, including community hospitals and academic hospitals, for at least 70% of the patients with follicular lymphoma, the frontline treatment is represented by bendamustine plus rituximab. Of course, when you move to the third line, you can use idelalisib, you can use copanlisib, and actually, there is another new PI3K inhibitor called duvelisib.

Transcript edited for clarity.