What is the recommended treatment for Cytomegalovirus (CMV) viremia in patients with lymphoma?

Treatment of CMV Viremia in Patients with Lymphoma

Oral valganciclovir is the first-line treatment for CMV viremia in patients with lymphoma, with intravenous ganciclovir reserved for cases with severe disease or concerns about absorption. 1

First-Line Treatment Options

• Oral valganciclovir: 900 mg twice daily (adjusted for renal function) is the preferred first-line treatment due to its excellent bioavailability and convenience 1
• Intravenous ganciclovir: 5 mg/kg twice daily should be used for patients with severe disease, concerns about gastrointestinal absorption, or very high viral loads 1
• Treatment should continue for at least 2 weeks and until CMV is no longer detectable by PCR 1

Monitoring During Treatment

• Weekly monitoring of CMV viral load by PCR is essential to assess treatment response 1, 2
• Regular monitoring for treatment-related adverse effects:
  • Neutropenia and thrombocytopenia with ganciclovir/valganciclovir 3
  • Renal function should be monitored, especially with foscarnet 2

Management of Treatment-Related Complications

• For severe neutropenia (ANC <500 cells/μL) during valganciclovir treatment:
  • Consider filgrastim (G-CSF) at 5 mcg/kg/day subcutaneously 3
  • Hold valganciclovir until ANC ≥1000/mm³, then resume at original dose if recovery occurs within 7 days 3
  • If neutropenia persists >7 days, consider dose reduction or alternative therapy 3

Second-Line Treatment Options

For CMV infections refractory to or intolerant of first-line therapy:

• Foscarnet: Recommended when ganciclovir is not tolerated due to myelosuppression 1, 2
• Cidofovir: Has shown response rates of 62% in primary pre-emptive therapy 1
• Maribavir: For refractory or resistant CMV infections with 56% clearance rate versus 24% with other agents (p<0.001) and significantly less nephrotoxicity than foscarnet (8.5% vs 21.3%) and less neutropenia than ganciclovir/valganciclovir (9.4% vs 33.9%) 1

Special Considerations for Lymphoma Patients

• CMV infections are common in patients with lymphoproliferative malignancies, especially those receiving:
  • T-cell suppressive therapy with purine analogs 1
  • Alemtuzumab therapy (highest risk 3-6 weeks after initiation when T-cell counts reach nadir) 1
• A small randomized study (n=40) showed that prophylactic valganciclovir significantly reduced CMV reactivation compared to valacyclovir (0% vs 35%, p=0.004) in patients with lymphoproliferative disease on alemtuzumab-containing regimens 1

Prevention Strategies

• Weekly CMV surveillance by PCR is recommended during alemtuzumab therapy and for at least 2 months after completion of treatment 1
• Pre-emptive therapy should be initiated upon confirmation of CMV viremia (defined as PCR positivity in ≥2 consecutive samples obtained 1 week apart) 1
• Acyclovir and valacyclovir are not recommended for CMV prophylaxis or treatment due to weak activity against CMV 2

Treatment Algorithm

1. Confirm CMV viremia: Two consecutive positive PCR tests one week apart 1
2. Assess severity and patient factors:
   • For non-severe disease with intact GI function: Oral valganciclovir 1
   • For severe disease or poor absorption: IV ganciclovir 1
3. Monitor weekly for treatment response 1, 2
4. Continue treatment for at least 2 weeks and until CMV is undetectable 1
5. For treatment failure or intolerance: Switch to foscarnet, cidofovir, or consider maribavir 1