Definition
Duvelisib is an oral PI3K inhibitor (phosphoinositide 3-kinase inhibitor) with selective activity against PI3K-δ (delta) and PI3K-γ (gamma) isoforms. It is used in the treatment of certain relapsed or refractory hematologic malignancies.
Mechanism of Action
- Inhibits PI3K-δ, reducing proliferation and survival of malignant B-cells.
- Inhibits PI3K-γ, modulating tumor microenvironment and decreasing pro-tumor immune signaling.
- Net effect: induces apoptosis in malignant lymphocytes and reduces survival signaling.
Indications (FDA-approved)
- Relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) after at least two prior therapies.
- Relapsed or refractory follicular lymphoma (FL) after at least two prior systemic therapies (accelerated approval; may be subject to withdrawal based on confirmatory trials).
Dosing
- Duvelisib 25 mg orally twice daily, continuous until disease progression or unacceptable toxicity.
- Taken with or without food.
Pharmacist-Relevant Toxicities
| Category | Key Concerns / Monitoring |
|---|---|
| Infections | Risk of serious/fatal infections (bacterial, viral, fungal, opportunistic); PJP and CMV prophylaxis may be required |
| Diarrhea / Colitis | Can be severe or fatal; monitor closely, manage with steroids or dose modification |
| Hepatotoxicity | Transaminase elevations; monitor LFTs |
| Cutaneous reactions | Severe rash, SJS/TEN reported |
| Pneumonitis | Non-infectious pneumonitis possible; monitor for cough, dyspnea |
| Myelosuppression | Neutropenia, anemia, thrombocytopenia—monitor CBC |
| Secondary malignancies | Risk of cutaneous malignancies; sun protection advised |
Drug Interactions
- Substrate of CYP3A4:
- Avoid strong inhibitors/inducers (may need dose adjustment).
- Avoid concurrent hepatotoxic or immunosuppressive agents when possible.
Pharmacist Counseling Points
- Take 25 mg BID continuously until progression/toxicity.
- Report diarrhea early; it can be severe and life-threatening.
- Infection prophylaxis (e.g., PJP, antiviral) may be needed.
- Avoid strong CYP3A4 modulators (e.g., ketoconazole, rifampin).
- Sun protection to lower risk of secondary skin cancers.
- Monitor CBC, LFTs, pulmonary symptoms regularly.