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 future of PI3K inhibitors in follicular lymphoma.

Novel PI3K inhibitors are currently in clinical development, says Leonard. Additionally, clinical trials are evaluating PI3K inhibitors in different dosing schedules, which could minimize toxicities associated with the agents, Leonard explains. Further study is needed to determine whether minimizing toxicity will result in improved efficacy because of fewer treatment discontinuations, Leonard says. 

PI3K inhibitors are unlikely to play a significant role in the up-front treatment of patients with follicular lymphoma because of the adverse effects they can cause, Leonard says. Although they will remain in the relapsed/refractory setting, it would be beneficial to identify which patient populations are more likely to benefit from PI3K inhibitors vs others, as well as what combinations, beyond those with CD20-directed antibodies, are optimal in this patient population, concludes Leonard.

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John P. Leonard, MD, discusses the future of PI3K inhibitors in follicular lymphoma.  



Dr. Leonard on the Future of 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. 

John P. Leonard, MD, discusses the potential for combination regimens with PI3K inhibitors in follicular lymphoma.  



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

John Leonard, MD, medical oncology, at Weill Cornell Medicine and NewYorkPresbyterian Hospital, discusses treatment considerations for patients with follicular lymphoma.

Current treatment options include rituximab and bendamustine, which have been around for sometime, as well as newer agents like obinutuzumab, says Leonard. There is also data that shows that idelalisib, a P13-kinase inhibitor, can work in rituximab-refractory patients, says Leonard. R-CHOP is another options as well as radioimmunotherapy and stem-cell transplant.

Several clinical are also investigating new agents in relapsed follicular lymphoma. These include the AUGMENT study, a double-blind randomized, parallel group study that is evaluating the efficacy and safety of lenalidomide in combination with rituximab in patients with relapsed or refractory follicular lymphoma.

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John Leonard, MD, medical oncology, at Weill Cornell Medicine and NewYorkPresbyterian Hospital, discusses follicular lymphoma treatment considerations. Treatment options include rituximab and bendamustine, which have been around for sometime, as well as newer agents like obinutuzumab, says Leonard.

John Leonard, MD

Articles

Dr. Leonard on the Future of PI3K Inhibitors in Follicular Lymphoma

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

Dr. John Leonard on Treatment Options for Relapsed Follicular Lymphoma