PV-CHP Chemo Protocol Summary

Polatuzumab vedotin: Pneumonia, URTI, neutropenia, thrombocytopenia, anemia, hypokalemia, peripheral neuropathy, diarrhea, nausea, constipation, vomiting, mucositis, abdominal pain, fatigue, infusion-related reaction.
Rituximab: Severe cytokine release syndrome, increased infective complications, progressive multifocal leukoencephalopathy.
Cyclophosphamide: Dysuria, hemorrhagic cystitis (rare), taste disturbances.
Doxorubicin: Cardiomyopathy, alopecia, urinary discoloration (red).
Prednisolone: Weight gain, GI disturbances, hyperglycemia, CNS disturbances, cushingoid changes, glucose intolerance.
Monitoring: FBC, U&E (including magnesium and calcium), glucose and LFTs prior to each cycle. Cardiac function (LVEF), hepatitis B status.

Neutrophil Criteria: $≥1x10^9/L$
Platelet Criteria: $≥75x10^9/L$
Hemoglobin Consideration: Consider transfusion if symptomatic or hemoglobin < 8g/dL.
Grade 3-4 Neutropenia:
- Withhold until ANC > 1000/µL.
- If ANC recovers by Day 7, resume without dose reduction.
- If ANC recovers after Day 7, consider reducing cyclophosphamide and/or doxorubicin by 25-50%.
Grade 3-4 Thrombocytopenia:
- Withhold until platelets > 75,000/µL.
- If platelets recover by Day 7, resume without dose reduction.
- If platelets recover after Day 7, consider reducing cyclophosphamide and/or doxorubicin by 25-50%.

Cyclophosphamide: No adjustment necessary.
Doxorubicin:
- Bilirubin < 30 µmol and AST/ALT 2-3xULN: 75% dose.
- Bilirubin 30-50 µmol and/or AST/ALT > 3xULN: 50% dose.
- Bilirubin 51-85 µmol: 25% dose.
- Bilirubin > 85 µmol: Omit.
Rituximab: No adjustment necessary.
Polatuzumab vedotin:
- Mild impairment (AST or ALT >1-2.5xULN or total bilirubin 1-1.5xULN): No adjustment.
- Moderate to severe: No information available.

Cyclophosphamide:
- Creatinine clearance > 20 ml/min: 100% dose.
- Creatinine clearance 10-20 ml/min: 75% dose.
- Creatinine clearance < 10 ml/min: 50% dose. (Consider mesna)
Doxorubicin:
- Creatinine clearance < 10 ml/min: 75% dose.
Rituximab: No adjustment necessary.
Polatuzumab vedotin:
- Creatinine clearance > 30 ml/min: 100% dose.
- Creatinine clearance < 30 ml/min: No information available.

Grade 2 Motor Neuropathy:
- Withhold until improvement to Grade ≤1.
- Restart at next cycle at 1.4mg/kg; if already at 1.4mg/kg, restart at 1.0mg/kg; if already at 1.0mg/kg, discontinue.
Grade 3 Motor Neuropathy:
- Withhold until improvement to Grade ≤1.
- Restart at next cycle at 1.4mg/kg; if already at 1.4mg/kg, restart at 1.0mg/kg; if already at 1.0mg/kg, discontinue.
Grade 2 Sensory Neuropathy:
- Reduce dose to 1.4mg/kg; if recurs, reduce to 1.0mg/kg; if already at 1.0mg/kg, discontinue.
Grade 3 Sensory Neuropathy:
- Withhold until improvement to Grade ≤2.
- Reduce to 1.4mg/kg; if already at 1.4mg/kg, reduce to 1.0mg/kg; if already at 1.0mg/kg, discontinue.
Grade 4 Motor or Sensory Neuropathy: Discontinue.

Grade 1-3: Interrupt, give supportive treatment. Discontinue permanently for first instance of Grade 3 wheezing, bronchospasm, or generalized urticaria, or for recurrent Grade 2 wheezing/urticaria, or recurrence of any Grade 3 symptoms. Resume at 50% rate upon resolution; escalate by 50 mg/hour every 30 minutes if no symptoms. Next cycle: infuse over 90 minutes, then 30 minutes if tolerated. Premedicate all cycles.
Grade 4: Stop immediately, give supportive treatment, permanently discontinue.

Monitor for new/worsening neurological, cognitive, or behavioral changes.
Withhold polatuzumab vedotin and concomitant chemotherapy if suspected; discontinue permanently if confirmed.

Doxorubicin: Discontinue if cardiac failure develops. Max lifetime cumulative dose is $450mg/m^2$ (or $400mg/m^2$ with prior mediastinal/pericardial radiotherapy).
Rituximab: Monitor for infusion-related reactions (cytokine release syndrome, hypersensitivity). Assess for cold/flu-like symptoms before treatment (hepatotoxicity risk). Monitor for PML.

21-day cycles for up to 6 cycles.
Cycle 1:
- Day 1: Rituximab $375mg/m^2$ IV, Prednisolone 100mg oral (Days 1-5)
- Day 2: Polatuzumab vedotin 1.8mg/kg IV, Cyclophosphamide $750mg/m^2$ IV, Doxorubicin $50mg/m^2$ IV
Cycles 2-6:
- Day 1: Rituximab $375mg/m^2$ IV, Polatuzumab vedotin 1.8mg/kg IV, Cyclophosphamide $750mg/m^2$ IV, Doxorubicin $50mg/m^2$ IV, Prednisolone 100mg oral (Days 1-5)

Extravasation Risk:
- Cyclophosphamide: Neutral
- Doxorubicin: Vesicant
- Polatuzumab vedotin: Neutral
- Rituximab: Neutral
Prednisolone: Take in the morning with or after food.
First polatuzumab vedotin infusion over 90 minutes, monitor for 90 minutes. Subsequent infusions may be given over 30 minutes if tolerated, followed by 30-minute monitoring.
Polatuzumab vedotin: Administer via sterile, non-pyrogenic, low protein binding 0.2µ or 0.22µ filter.
Rituximab: Refer to administration guidelines.

Antiemetics: Ondansetron 8mg IV/PO 15-30 minutes pre-chemo. Metoclopramide 10mg PO PRN, Ondansetron 8mg PO BID x3 days (take home).
Rituximab/Polatuzumab vedotin Pre-medication: Chlorphenamine 10mg IV & Paracetamol 1000mg PO 30 minutes prior. Prednisolone 100mg PO on morning of treatment and for 4 days after.
Infusion Reactions: Hydrocortisone 100mg IV PRN (Rituximab), Salbutamol 2.5mg nebule PRN (bronchospasm), Pethidine 25-50mg IV PRN (rigors).
Growth Factors: Filgrastim/Lenograstim/Pegfilgrastim (per formulary) from Day 6 for 7 days (or Pegfilgrastim on Day 2).
Allopurinol: 300mg PO daily x7 days (1st cycle only).
Anti-infective Prophylaxis: Aciclovir 400mg PO BID, Co-trimoxazole 960mg PO MWF.
Mouthwashes: As per policy for mucositis.
Gastric Protection: PPI or H2 antagonist (high risk patients).