Duvelisib

Duvelisib is an oral small-molecule inhibitor of phosphoinositide 3-kinase (PI3K) that selectively targets the delta and gamma isoforms (PI3K-δ and PI3K-γ). By inhibiting PI3K signaling in malignant B and T cells and their microenvironment, it aims to reduce tumor cell survival and disrupt tumor-supportive interactions.

In the United States, duvelisib was approved by the FDA in 2018 for adults with relapsed or refractory follicular lymphoma after at least two prior systemic therapies. The drug has been studied in other B-cell malignancies, including chronic lymphocytic leukemia/small lymphocytic lymphoma and mantle cell lymphoma, but approvals have primarily centered on follicular lymphoma; use in other indications varies by country and guidelines.

Duvelisib carries significant safety concerns. The FDA assigns boxed warnings for serious or life-threatening infections, hepatotoxicity, and severe or fatal diarrhea/colitis; additional risks include pneumonitis, intestinal perforation, rash, and other immune-mediated toxicities. Because of these risks, a risk evaluation and mitigation strategy (REMS) is in place for surveillance and patient management. Common adverse events reported in trials include diarrhea, rash, nausea, fatigue, and cytopenias; serious infections and liver enzyme elevations can occur. Caution is advised with concomitant immunosuppressants and strong inhibitors or inducers of CYP3A4, and patients require monitoring for infection, liver function, and gastrointestinal symptoms.

Duvelisib is a substrate of CYP3A4 and is administered orally; dose adjustments are made for hepatic impairment and drug interactions as per labeling.