Dr. Leonard on the Potential for Combinations With PI3K Inhibitors in Follicular Lymphoma

John P. Leonard, MD, The Richard T. Silver Distinguished Professor of Hematology and Medical Oncology, professor of medicine, executive vice chairman, Department of Medicine, senior associate dean for Innovation and Initiatives, Weill Cornell Medicine, attending physician, NewYork-Presbyterian Hospital, discusses the potential for combination regimens with PI3K inhibitors in follicular lymphoma.

Currently, the FDA-approved PI3K inhibitors—copanlisib (Aliqopa), idelalisib (Zydelig), duvelisib (Copiktra), and umbralisib (Ukoniq)—are reserved for patients with relapsed/refractory follicular lymphoma, Leonard says. Moreover, the agents are typically utilized following chemotherapy with or without a CD20-directed antibody, Leonard says. Then, patients may receive an additional CD20-directed antibody, such as rituximab (Rituxan), in combination with chemotherapy or lenalidomide (Revlimid) as second-line therapy, Leonard says. PI3K inhibitors are considered following one or more lines of prior chemoimmunotherapy in patients who are often refractory to rituximab and lenalidomide, Leonard explains.

However, findings from the phase 3 CHRONOS-3 trial (NCT02367040) demonstrated a median progression-free survival of 21.5 months with copanlisib in combination with rituximab vs 13.8 months with rituximab plus placebo in patients with relapsed/refractory indolent non-Hodgkin lymphoma, including follicular lymphoma, Leonard says. As such, it is possible that combination strategies featuring PI3K inhibitors will move into earlier lines of therapy, concludes Leonard.