- Class: Antimetabolite – purine analog / adenosine deaminase (ADA) inhibitor
Mechanism of Action (MOA)
- Inhibits adenosine deaminase (ADA) → ↑ intracellular adenosine and deoxyadenosine.
- Accumulated deoxyadenosine nucleotides → inhibit DNA synthesis and repair.
- Cytotoxic mainly to lymphocytes, especially T-cells.
Clinical Uses
- Hairy cell leukemia (HCL) → standard first-line therapy.
- Investigated/used off-label in: chronic lymphocytic leukemia (CLL), cutaneous T-cell lymphoma, GVHD prophylaxis (in transplant settings).
Dosing (Adults)
- 4 mg/m² IV q2 weeks.
- Given as slow IV infusion (over 20–30 min).
- Continue until complete response or maximum of ~6 months.
Important:
- Do NOT give with other purine analogs (e.g., fludarabine, cladribine) → risk of fatal immunosuppression.
- Requires prophylaxis for opportunistic infections (e.g., PCP, HSV, VZV).
Toxicities
- Myelosuppression (neutropenia, anemia, thrombocytopenia).
- Immunosuppression → risk of opportunistic infections.
- Nausea, vomiting, diarrhea.
- Hepatotoxicity (↑ LFTs).
- Nephrotoxicity (dose adjust in renal impairment).
- Rare: pulmonary toxicity.
Monitoring
- CBC with differential (before each dose).
- Renal and hepatic function tests.
- Signs of infection (consider antimicrobial prophylaxis).
- Response assessment in HCL: CBC recovery, bone marrow biopsy if indicated.
Summary
Pentostatin (Nipent®) is a purine analog / ADA inhibitor mainly used in hairy cell leukemia. It causes profound immunosuppression, requiring infection prophylaxis and close monitoring. Should not be combined with other purine analogs due to risk of severe/fatal toxicity.