What are the guidelines for ruling out active infections, including military tuberculosis, before initiating treatment with atezolizumab (anti-PD-L1 monoclonal antibody) and bevacizumab (vascular endothelial growth factor inhibitor) for hepatocellular carcinoma (HCC)?

Guidelines for Ruling Out Active Infections Before Initiating Atezolizumab Plus Bevacizumab for HCC

Before initiating atezolizumab plus bevacizumab therapy for hepatocellular carcinoma, patients must undergo screening for active infections, particularly esophageal varices, and receive appropriate treatment according to institutional guidelines. 1

Pre-Treatment Infection Screening Requirements

Endoscopic Evaluation for Varices

• Gastrointestinal bleeding is a known adverse effect of bevacizumab, requiring mandatory endoscopic evaluation and treatment of esophageal varices before initiating therapy 1
• Patients with portal hypertension should have had upper GI endoscopy within 6 months and adequately treated varices prior to starting treatment 1
• Untreated or incompletely treated esophageal or gastric varices with bleeding or high risk for bleeding are absolute contraindications to therapy 1

Viral Hepatitis Screening

• Patients must be screened for hepatitis B virus (HBV) and hepatitis C virus (HCV) co-infection 1
• Co-infection with both HBV and HCV was an exclusion criterion in the IMbrave150 trial that established this regimen as standard of care 1
• For patients with chronic viral hepatitis, appropriate antiviral therapy should be initiated before immunotherapy to prevent viral reactivation 1

Tuberculosis Screening

• While not explicitly mentioned in HCC-specific guidelines, standard pre-immunotherapy screening should include evaluation for latent or active tuberculosis 1
• Screening typically involves tuberculin skin testing or interferon-gamma release assay (IGRA), with chest imaging for those with positive results 1

Other Contraindications Related to Immune Status

• History of autoimmune diseases is a contraindication for atezolizumab therapy 1
• Previous allogeneic stem cell or solid organ transplantation precludes the use of atezolizumab 1
• Idiopathic pulmonary fibrosis or pneumonitis are contraindications for immunotherapy 1

Treatment Algorithm for Infection Screening

1. Initial Laboratory Screening:

   • Complete blood count with differential 1
   • Comprehensive metabolic panel 1
   • Hepatitis B surface antigen, surface antibody, and core antibody 1
   • Hepatitis C antibody with reflex PCR if positive 1
   • HIV testing 1
   • Tuberculosis screening (PPD or IGRA) 1

2. Imaging Studies:

   • Chest radiograph to evaluate for pulmonary infections or tuberculosis 1
   • Consider chest CT for patients with positive TB screening tests 1

3. Endoscopic Evaluation:

   • Upper GI endoscopy within 6 months before treatment initiation 1
   • Treatment of any identified varices according to standard guidelines 1

4. Clinical Assessment:

   • Evaluation for signs and symptoms of active infection 1
   • Review of autoimmune disease history 1
   • Assessment of immunosuppressive medication use 1

Common Pitfalls and Caveats

• Bleeding Risk: The risk of variceal bleeding with bevacizumab is significant, with 10% of patients experiencing grade ≥3 bleeding events in post-approval studies, including 2% with fatal outcomes 2
• Autoimmune Conditions: Patients with active or previously documented autoimmune disease should carefully consider the risk of immune-related adverse effects associated with atezolizumab 1
• Treatment Alternatives: For patients with contraindications to atezolizumab plus bevacizumab, alternative first-line therapies include sorafenib, lenvatinib, or durvalumab 1
• Child-Pugh Classification: Most clinical trials were limited to Child-Pugh A patients, with limited data on efficacy and safety in Child-Pugh B or C patients 1
• Monitoring Requirements: Ongoing monitoring for infections during treatment is essential, particularly in cirrhotic patients who are immunocompromised 1

Special Considerations for Specific Patient Populations

• Patients with Cirrhosis: Higher risk of infections and bleeding complications; require more intensive monitoring 1
• Transplant Recipients: Atezolizumab is contraindicated in patients with prior solid organ transplantation 1
• Hepatitis B Carriers: Require prophylactic antiviral therapy before and during immunotherapy 1
• Patients with Prior Immunotherapy: Those who experienced immune-related adverse events with previous immunotherapy require careful evaluation 1

By following these comprehensive screening guidelines, clinicians can minimize the risk of serious complications related to infections when initiating atezolizumab plus bevacizumab therapy for hepatocellular carcinoma.