Insights From:Bruce D. Cheson, MD, FACP, FAAAS, Georgetown University Hospital; Shuo Ma, MD, PhD, Northwestern University Feinberg School of Medicine; Richard R. Furman, MD, Weill Cornell Medical College
Shuo Ma, MD, PhD: Another interesting agent is venetoclax. Venetoclax is an inhibitor of BCL-2, the anti-apoptotic protein. Venetoclax is the selective orally available BCL-2 inhibitor that has shown activity in CLL as well as lymphomas. At ASH 2015, there's an update reported with venetoclax single-agent treatment in relapsed/refractory non-Hodgkin lymphoma; 106 patients were included in this study, of whom about 30 patients have follicular lymphoma. The response rate was about 30% for the follicular lymphoma patients, and about 10% had a complete response rate.
This shows that the blocking of BCL-2 is a potential treatment option for follicular lymphoma patients, and I'm sure there will be a lot of different combinations trying to add to this new agent.
Bruce Cheson, MD: The checkpoint inhibitors are drugs that reactivate a dormant immune system. When you've got a tumor, it's like Ambien for our killer T-cells in macrophage—it puts them to sleep. These are drugs which impact the PD-1/PD-L1 axis. And when they inhibit that, the effector cells, the killer cells, rise up and kill the tumors. These drugs—these checkpoint inhibitors—have now been approved for a number of solid tumors. They have demonstrated incredible activity in Hodgkin lymphoma, for nivolumab, a response rate of 87%, or so, in relapsed/refractory patients.
And they are now just being looked at in follicular lymphoma. We do know that in follicular lymphoma, you've got a microenvironment, which is full of effector cells. So the potential is, if you can energize them—wake them up—they may be effective in the treatment of follicular lymphoma. By themselves, the response rates have been modest. The data are sparse; the response rates are modest.
But we are now testing these in combination with other drugs. For example, we have a number of trials combining a drug, which is a checkpoint inhibitor, with, for example, a BTK inhibitor, or a PI3K inhibitor, or even a BCL-2 inhibitor. But there are so many checkpoint inhibitors out there and so many BTK and PI3K inhibitors. It keeps clinical trials in business for a long time. There are all these combinations and permutations. But we'd certainly like to define the best combination for our patients. And this is going to require a lot of correlative science along with the clinical trials so we can better understand the relationship of these drugs to the host and the host microenvironment, and biomarkers. We need to learn more, and then we will develop better regimens for follicular lymphoma that incorporate these sorts of agents. Transcript Edited for Clarity