Radhakrishnan Ramchandren, MD: The CHRONOS studies looked at a PI3-kinase inhibitor called copanlisib in relapsed/refractory follicular lymphoma. In these studies, the thought process behind the agent, which inhibits both PI3K delta and alpha, is that alpha upregulation may be a potential mechanism for resistance of PI3-kinase in this population. The other approved agent in this population, idelalisib, inhibits PI3K delta, specifically. So, that was the rationale behind this particular study.

This study evaluated 142 patients with indolent lymphoma. The majority had follicular lymphoma. It’s important to note that the majority of patients responded to this therapy—59% of patients saw at least a partial response, with the vast majority of patients having tumor reduction, as a whole. From a toxicity point of view, this study did demonstrate some similar and some dissimilar toxicities with idelalisib and other PI3K delta kinase inhibitors.

The long-term update at the ASH annual meeting demonstrated no additional significant toxicities with longer follow-up in this population, as compared with the original paper that published in the Journal of Clinical Oncology in 2017.

This is important with this class of agents because many of these adverse events—particularly pneumonitis, colitis, and other immune events, as well as infectious events—may develop over time rather than with initial therapy. And so, longer follow-up with these novel agents may be important to fully compare both toxicity and activity.

In terms of patient selection, the side effect profile is slightly different. Hyperglycemia, hypertension, and headache all may correspond to copanlisib. This is not typically seen with idelalisib. Based on the toxicity profiles of the drugs, I would suggest that those be taken into consideration when choosing these agents for patients. These drugs have not been compared in a head-to-head format, so it’s difficult to say that one is better or more effective than another at this time. I would recommend the use of this agent in patients who have relapsed/refractory follicular lymphoma, who have relapsed after at least 2 prior lines of therapy, per the FDA approval.

Transcript Edited for Clarity