Insights From: Bruce Cheson, MD, Lombardi Comprehensive Cancer Center; Anas Younes, MD, Memorial Sloan Kettering Cancer Center
Anas Younes, MD: Follicular lymphoma is a chronic lymphoid malignancy. It’s really unique because although it is not curable, it is treatable. The average lifespan these days is about 18 to 20 years, so any patient would require multiple treatments in their lifespan. The more active treatments we have down the line, the longer the patient’s survival will be. But it’s an irritating disease, and the patients don’t like to come back and forth even though we tell them it’s not life-threatening. It’s a chronic disease, but the anxiety and the inconvenience of coming back and forth for multiple treatments in a lifespan is not ideal. So, I think we should focus on improving the frontline regimens that can give you longer progression-free survival, even though they may not cure you. If they give you 15 years to first remission, it’s better than having 6 or 7 years to first remission. Whether or not maintenance is involved, it doesn’t matter, but I think we should focus on improving the outcome of frontline regimens in the next few years.
Bruce Cheson, MD: Where copanlisib fits in to the clinical management of patients with follicular and low-grade lymphoma remains to be defined. Its activity appears to be comparable to idelalisib. Will it supplant idelalisib? Well, if it is indeed less toxic, it might, but I think the major issue is the schedule of administration, which is 3 weeks in a row and then a week off. To do this indefinitely, you’re going to have problems with patient compliance.
It would be prudent to develop a strategy where you could discontinue this drug after a finite period of time. We’re running into this with all the new agents—ibrutinib, idelalisib—that are given virtually indefinitely. Patient compliance and expense become major issues, and so it would be wise to find a truncated program that would also help it in its competition with the other PI3 kinase inhibitors out there. There are still others we haven’t talked about, such as TGR-1202s, umbralisib, which doesn’t seem to have any of these adverse effects because of the differential effect on T-regulatory cells. But, again, we haven’t seen long-term follow-up with that drug either.
So, it’s going to be an important time in the evaluation of these drugs. Clinical trials are critical, close follow-up is important, and publication of the data will be important to educate physicians in the community as to where to best use the drugs. What we have learned from the idelalisib experience is that patients who receive it early in the course of the disease—such as frontline, younger patients who have an intact immune system—tend to have greater toxicity. Are we going to see that with copanlisib? I have no idea. So, if one of the objects is to move a drug to the frontline, then you have to be very, very careful with a drug in the same class.
The goal of treatment is not to wait for patients to be refractory, not to wait for patients to relapse. It is to develop the most effective, yet least toxic, induction strategies. Fewer patients progress, increasing the chance that we may actually be curing patients with follicular and low-grade lymphomas.