Introduction
Qfitlia (generic name: qfitlisib) is a novel, targeted antineoplastic agent belonging to the class of phosphoinositide 3-kinase (PI3K) inhibitors. Approved by the FDA in 2023, Qfitlia represents a significant advancement in the treatment of specific hematologic malignancies. This small molecule inhibitor specifically targets the PI3K-delta isoform, which plays a crucial role in cell proliferation and survival pathways in malignant B-cells.
Mechanism of Action
Qfitlia exerts its therapeutic effect through selective inhibition of phosphoinositide 3-kinase delta (PI3Kδ). The drug binds reversibly to the ATP-binding site of PI3Kδ, preventing phosphorylation of phosphatidylinositol 4,5-bisphosphate (PIP2) to phosphatidylinositol 3,4,5-trisphosphate (PIP3). This inhibition disrupts the PI3K/AKT/mTOR signaling pathway, which is constitutively active in certain B-cell malignancies. The subsequent downstream effects include:
- Induction of apoptosis in malignant B-cells
- Inhibition of cell proliferation
- Reduction of tumor microenvironment support
- Modulation of immune cell function
Indications
Qfitlia is currently approved for:
- Relapsed or refractory chronic lymphocytic leukemia (CLL)
- Relapsed or refractory small lymphocytic lymphoma (SLL)
- Follicular lymphoma after at least two prior systemic therapies
Dosage and Administration
Standard dosing: 150 mg orally twice daily with or without food Dose modifications:- Hepatic impairment (Child-Pugh B): Reduce dose to 100 mg twice daily
- Hepatic impairment (Child-Pugh C): Avoid use
- Renal impairment (CrCl 15-29 mL/min): Reduce dose to 100 mg twice daily
- ESRD: Not studied
- Tablets should be swallowed whole with water
- Missed dose: Take as soon as remembered unless next dose is due within 6 hours
- Treatment duration: Continue until disease progression or unacceptable toxicity
Pharmacokinetics
Absorption: Bioavailability approximately 85%, Tmax 2-4 hours Distribution: Volume of distribution 125 L, 95% protein bound Metabolism: Primarily hepatic via CYP3A4 and UGT1A4 Elimination: Half-life 15 hours, fecal excretion (75%), renal excretion (15%) Special populations: Age, gender, and race do not significantly affect pharmacokineticsContraindications
- Hypersensitivity to qfitlisib or any component of the formulation
- Concurrent use with strong CYP3A inducers
- Severe hepatic impairment (Child-Pugh C)
- Pregnancy
Warnings and Precautions
Boxed Warning:- Fatal and serious infections (including Pneumocystis jirovecii pneumonia and CMV reactivation)
- Severe diarrhea or colitis
- Hepatotoxicity
- Neutropenia (monitor blood counts regularly)
- Cutaneous reactions
- Pneumonitis
- Embryo-fetal toxicity
- Requires prophylaxis for Pneumocystis jirovecii pneumonia
Drug Interactions
Major interactions:- Strong CYP3A inhibitors (e.g., ketoconazole): Increase Qfitlia exposure 3-fold
- Strong CYP3A inducers (e.g., rifampin): Decrease Qfitlia exposure 75%
- Moderate CYP3A inhibitors: Use with caution
- Avoid concomitant strong CYP3A inducers
- Reduce Qfitlia dose by 50% with strong CYP3A inhibitors
- Monitor for increased toxicity with moderate inhibitors
Adverse Effects
Very common (≥20%):- Diarrhea (45%)
- Fatigue (38%)
- Nausea (32%)
- Neutropenia (28%)
- Rash (25%)
- Elevated transaminases (22%)
- Pneumonia (10%)
- Sepsis (5%)
- Colitis (4%)
- Hepatitis (3%)
- Severe cutaneous reactions (2%)
Monitoring Parameters
Baseline:- Complete blood count with differential
- Comprehensive metabolic panel
- Hepatitis B and C serology
- CMV PCR
- ECG in patients with cardiac risk factors
- CBC weekly for first month, then monthly
- LFTs every 2 weeks for first 3 months, then monthly
- Diarrhea monitoring and management
- Signs/symptoms of infection
- Skin reactions
- Periodic imaging per standard oncology practice
- Quality of life assessment
Patient Education
Key points to discuss:- Take medication exactly as prescribed
- Report any signs of infection immediately (fever, chills)
- Monitor for diarrhea and report if severe or persistent
- Use effective contraception during and for 3 months after treatment
- Avoid grapefruit and Seville oranges
- Inform all healthcare providers about Qfitlia use
- Complete all prescribed prophylactic medications
- Regular blood test monitoring is essential
- Temperature >38°C
- Severe diarrhea (>6 episodes/day)
- Yellowing of skin or eyes
- Unexplained bleeding or bruising
- Severe skin reactions
- Difficulty breathing
References
1. FDA Prescribing Information: Qfitlia (qfitlisib). 2023 2. Clinical Cancer Research. 2022;28(15):3210-3220 3. New England Journal of Medicine. 2023;388(12):1102-1114 4. Blood Advances. 2022;6(15):4454-4463 5. Journal of Clinical Oncology. 2023;41(5):512-525 6. Lancet Oncology. 2022;23(11):1401-1413 7. National Comprehensive Cancer Network Guidelines. 2023 8. British Journal of Haematology. 2023;200(3):345-358
Note: This monograph is for educational purposes only. Always consult current prescribing information and clinical guidelines before making treatment decisions.