Is it safe to administer polatuzumab vedotin (polatuzumab vedotin) with R-CHP (rituximab, cyclophosphamide, doxorubicin, and prednisone) to patients over 80 years old?

Polatuzumab Vedotin-R-CHP in Patients Over 80 Years Old

Yes, polatuzumab vedotin with R-CHP (Pola-R-CHP) can be administered to patients over 80 years old with diffuse large B-cell lymphoma, but requires dose reduction of chemotherapy agents (not polatuzumab vedotin), comprehensive geriatric assessment, mandatory G-CSF prophylaxis, and close monitoring for treatment-related mortality. 1, 2

Evidence Supporting Use in Patients >80 Years

The most recent real-world data from 2025 demonstrates that Pola-R-CHP is both effective and feasible in this age group:

• Overall response rates of 89.5% were achieved in patients ≥80 years, comparable to younger patients (97.3% in <80 years) 2
• 12-month overall survival of 86.2% and progression-free survival of 78.5% were observed in patients >80 years receiving reduced-dose Pola-R-CHP 1
• The POLARIX subgroup analysis showed clinically meaningful PFS improvements across all older age groups, with particularly strong benefit in patients ≥70 years (37% reduction in risk of progression, relapse, or death; HR 0.63) 3

Critical Dose Modification Strategy

The key to safe administration is selective dose reduction:

• Reduce doxorubicin and cyclophosphamide doses based on geriatric assessment and comorbidities 2
• Maintain full-dose polatuzumab vedotin (1.8 mg/kg) whenever possible, as dose reduction was not required for peripheral neuropathy in the >80 cohort 1
• Median initial dose intensity and average relative dose intensity for cytotoxic agents were markedly lower in patients ≥80 years, while Pola dosing was relatively preserved 2

This approach aligns with established ESMO guidelines recommending attenuated chemotherapy (R-miniCHOP) or substitution/omission of doxorubicin in patients >80 years who are frail or have cardiac dysfunction 4

Mandatory Risk Mitigation Measures

1. Comprehensive Geriatric Assessment

Perform before treatment initiation to identify high-risk patients: 4

• Assess comorbidities, functional status (ECOG performance status), and cognitive function 4
• Geriatric Nutritional Risk Index (GNRI) is critical: Lower GNRI independently correlates with both reduced overall response and increased severe adverse events 2
• Patients with ECOG 3-4 should not receive Pola-R-CHP and require palliative approaches or less intensive regimens 5

2. Prophylactic G-CSF is Mandatory

• Not optional in elderly patients receiving Pola-R-CHP 5, 3
• Febrile neutropenia rates are elevated: 32% in reduced-dose cohorts 1 and 16.3% in patients ≥60 years (vs 7.6% with R-CHOP) 3
• Risk increases substantially with average relative dose intensity <70%, even with dose reductions 1
• ESMO guidelines emphasize that highest treatment-related mortality occurs within first two cycles 5

3. Close Monitoring for Treatment-Related Mortality

Treatment-related mortality is significantly higher in patients ≥80 years:

• TRM of 11.4% in ≥80 years vs 2.3% in <80 years 2
• Most deaths occur early in treatment course 5
• Adequate supportive care is essential to prevent treatment-related mortality, particularly in first two cycles 5

Safety Profile Considerations

The safety profile in older patients is manageable but requires vigilance:

• Grade 3-4 adverse events occur in approximately 63% of patients ≥60 years (similar between Pola-R-CHP and R-CHOP) 3
• Grade 3-5 infections: 15.0% with Pola-R-CHP vs 12.9% with R-CHOP in patients ≥60 years 3
• Peripheral neuropathy is generally mild: In the phase 1b/2 study, 27% had grade 1,11% grade 2, and only 3% grade 3 peripheral neuropathy 6
• No novel toxicities were reported in older age groups 3

Contraindications and When NOT to Use Pola-R-CHP

Do not administer Pola-R-CHP in patients >80 years with:

• ECOG performance status 3-4 5
• Severe cardiac dysfunction precluding any anthracycline exposure 4
• Low GNRI indicating severe malnutrition 2
• Inability to provide adequate supportive care and close monitoring 5

In these cases, consider R-miniCHOP, omission of doxorubicin, or substitution with gemcitabine/etoposide/liposomal doxorubicin as recommended by ESMO guidelines 4

Practical Treatment Algorithm

For fit patients >80 years:

1. Perform comprehensive geriatric assessment including GNRI 2
2. If ECOG 0-2 and adequate nutrition: Proceed with reduced-dose Pola-R-CHP 1, 2
3. Reduce doxorubicin and cyclophosphamide by 20-30% based on comorbidities 2
4. Maintain full-dose polatuzumab vedotin 1.8 mg/kg 1
5. Mandatory prophylactic G-CSF from cycle 1 5, 3
6. Intensive monitoring during first two cycles 5

For frail patients >80 years:

1. Consider R-miniCHOP or modified regimens with doxorubicin substitution/omission 4
2. Clinical trial enrollment when available 4

Common Pitfalls to Avoid

• Do not reduce polatuzumab vedotin dose preemptively based on age alone—maintain 1.8 mg/kg unless toxicity develops 1
• Do not omit G-CSF prophylaxis—this is mandatory, not optional, in elderly patients 5, 3
• Do not use appearance alone to judge fitness—comprehensive geriatric assessment is required 5
• Do not maintain full-dose cytotoxic chemotherapy in very elderly patients—selective dose reduction of doxorubicin/cyclophosphamide improves tolerability 1, 2
• Do not discharge patients immediately after first cycle without adequate observation and supportive care planning 5