Duvelisib — Drug Monograph
Brand names: Copiktra
Drug class: PI3K Inhibitor
Mechanism of Action
Duvelisib is an oral dual inhibitor of the Class I PI3K-delta and PI3K-gamma isoforms. PI3K-delta is primarily expressed in leukocytes and is critical for B-cell proliferation and survival, while PI3K-gamma is involved in the recruitment and activation of supportive immune cells in the tumor microenvironment. Dual inhibition disrupts both autonomous B-cell signaling and the protective signals provided by the microenvironment. This results in decreased growth and survival of malignant B-lineage cells.
FDA Indications
- Treatment of adult patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) after at least two prior therapies
Common Side Effects
- Diarrhea/Colitis
- Neutropenia
- Rash
- Fatigue
- Pyrexia
- Cough
- Nausea
- Upper respiratory tract infection
- Anemia
- Thrombocytopenia
- Musculoskeletal pain
Clinical Pearl
Duvelisib's dual delta/gamma inhibition is thought to differentiate it from delta-only inhibitors, but it carries significant immune-mediated toxicities. The Black Box Warnings for colitis and pneumonitis reflect its potent modulation of the immune system; these side effects often require permanent discontinuation or high-dose corticosteroids. PJP prophylaxis is mandatory while on therapy. In 2021/2022, several PI3K inhibitors, including duvelisib, had their indications for follicular lymphoma…
Related Therapies & Mechanisms
- Copanlisib (Aliqopa) — PI3K Inhibitor · Lymphoma
- Acalabrutinib (Calquence) — Lymphoma
- Alemtuzumab (Campath) — Leukemia
- Bendamustine (Treanda) — Lymphoma