“With current therapies, the median survival for people with follicular lymphoma [FL] is about 20 years. Most people with FL will live as long as the general population, as it is a disease of morbidity more than mortality. That said, there is still room for improvement,” said formal CHRONOS-3 discussant Peter Martin, MD, of NewYork-Weill Cornell Medicine Medical Center, New York.
“Over the past decade, there have been 14 new drugs approved for FL. As single agents, most are effective for about a year. This prompts an ongoing search for new therapies and rational combinations. Most of us who treat lymphoma know the puzzle is still not solved,” continued Dr. Martin.
Peter Martin, MD
Striking a Balance Between Activity and Safety
Four PI3K inhibitors are approved for the treatment of FL: idelalisib, umbralisib, duvelisib, and copanlisib. Although all agents demonstrated significant and comparable activity in FL, Dr. Martin noted some differences in adherence rates and safety profiles.
“Safety profiles are relevant to indolent NHL. In some instances, inhibition of regulatory T cells may increase antitumor activity but result in loss of self-tolerance as well [eg, liver enzymes, diarrhea]. All of these agents are potentially associated with autoimmune toxicities and also with infections and infection-related deaths,” he explained.
“The management of indolent NHL is about balance. We hope to minimize lymphoma-related symptoms while minimizing treatment-related side effects. The question is whether CHRONOS-3 strikes that balance. We have a hint in that copanlisib is the first PI3K inhibitor to be safely combined with rituximab in a phase III study in indolent NHL,” Dr. Martin stated.
DISCLOSURE: Dr. Martin has served as a consultant or advisor to Bayer, BeiGene, Celgene, Cellectar, IMAB, Janssen, Karyopharm, Kite Pharma, Kite/Gilead, MorphoSys, Regeneron, Sandoz, TeneoBio, and Verastem; has received institutional research funding from Karyopharm; and has been reimbursed for travel, accommodations, or other expenses by Janssen.
The combination of the PI3K inhibitor copanlisib plus the monoclonal antibody rituximab reduced the risk of disease progression or death by 48% compared with placebo plus rituximab in patients with relapsed indolent non-Hodgkin lymphoma (NHL), according to the results of the phase III CHRONOS-3...