What are the implications of Cytomegalovirus (CMV) infection in adults?

From the Guidelines

For adults with CMV infection, particularly those who are immunocompromised, the use of letermovir as prophylaxis is recommended, as it has been shown to significantly reduce the incidence of CMV reactivation and disease in allogeneic HCT recipients, with a lower toxicity profile compared to other CMV-targeted drugs 1.

Key Considerations for CMV Infection Management

• CMV infections are a significant concern in patients with cancer, especially those undergoing allogeneic hematopoietic cell transplantation (HCT) or receiving T-cell depleting therapies like alemtuzumab.
• The risk of CMV reactivation and disease is highest among HCT recipients with CMV-seropositive status prior to transplant, with an incidence of reactivation ranging from 50% to 60% and CMV disease in about 10%–30% of seropositive recipients 1.
• Letermovir has been demonstrated to be effective in reducing the incidence of prophylaxis failure and clinically significant CMV infection in allogeneic HCT recipients, with a well-tolerated safety profile 1.
• For pre-emptive therapy, valganciclovir and ganciclovir are considered the agents of choice, with foscarnet used for patients who cannot tolerate ganciclovir or as second-line therapy 1.

Treatment and Prophylaxis Recommendations

• Letermovir is recommended for prophylaxis in high-risk adults, such as those undergoing allogeneic HCT, at a daily dose of 480 mg (or 240 mg in patients taking ciclosporin) for 14 weeks after transplantation 1.
• For symptomatic CMV infection, first-line treatment includes ganciclovir or oral valganciclovir, with alternative medications like foscarnet or cidofovir considered for resistant cases.
• Regular monitoring of CMV viral load is crucial for early detection of reactivation and prompt initiation of treatment in high-risk patients.

From the FDA Drug Label

1 INDICATIONS & USAGE

1.1 Adult Patients Treatment of Cytomegalovirus (CMV) Retinitis: Valganciclovir tablets, USP are indicated for the treatment of CMV retinitis in patients with acquired immunodeficiency syndrome (AIDS) [see Clinical Studies ( 14. 1)]. Prevention of CMV Disease: Valganciclovir tablets, USP are indicated for the prevention of CMV disease in kidney, heart, and kidney-pancreas transplant patients at high risk (Donor CMV seropositive/Recipient CMV seronegative [D+/R-]) [see Clinical Studies ( 14.1)].

Valganciclovir is indicated for the treatment of CMV retinitis in adults with AIDS and for the prevention of CMV disease in high-risk adult transplant patients, such as those with a D+/R- serostatus 2.

• Treatment: CMV retinitis in adults with AIDS
• Prevention: CMV disease in high-risk adult transplant patients (D+/R-)

From the Research

CMV Infection in Adults

• CMV infection in healthy adults is usually asymptomatic or causes a mild mononucleosis-like syndrome 3
• However, CMV disease can cause significant morbidity and mortality in neonates and severely immunocompromised adults 3, 4
• The incidence of severe CMV disease in immunocompetent adults appears to be greater than previously thought, which may be partly due to immune dysfunction related to comorbidities such as kidney disease or diabetes mellitus 3

Diagnosis and Treatment

• Non-invasive testing for CMV is widely available and can facilitate early diagnosis if used appropriately 3
• Current evidence suggests that targeted antiviral therapy with ganciclovir or valganciclovir is appropriate for severe CMV disease in immunocompetent adults 3, 5
• However, the decision to treat CMV infection depends mainly on the immune status of the host, with symptomatic treatment recommended for immunocompetent patients and antiviral therapy and immunotherapy recommended for immunocompromised patients 4
• New antiviral compounds with new mechanisms of action, such as artesunate, leflunomide, letermovir, and maribavir, are being investigated in clinical studies 6

Management of Ganciclovir Resistance

• Ganciclovir resistance poses a major challenge in solid organ transplant recipients, with a development of resistance associated with increased morbidity and mortality 7
• Second-line options to treat ganciclovir resistance include foscarnet and cidofovir, but these drugs are often poorly tolerated due to high rates of toxicity 7
• CMV immunoglobulin and leflunomide have been used to treat ganciclovir-resistant CMV infection in cardiothoracic transplant recipients, with reported success 7