Clinical bottom line
Anti-CD20 monoclonal antibody therapies, increasingly used in hematologic malignancies, autoimmune diseases, and neurologic disorders, carry a heightened risk of infectious complications, notably hepatitis B virus (HBV) reactivation and bacterial sinusitis. Careful pre-treatment screening, vigilant monitoring, and prophylactic strategies are essential to mitigate these risks. Current evidence supports protocol-driven HBV serological screening and antiviral prophylaxis in at-risk patients, while emerging data highlight the need for awareness of upper respiratory infections, including rhinosinusitis, during therapy. Clinicians should balance immunosuppressive benefits with infection risk, tailoring management to individual patient profiles.
What the evidence shows
Anti-CD20 monoclonal antibodies target the CD20 antigen on B cells, leading to B cell depletion and immunomodulation (Anti-CD20 monoclonal antibody, 2020). This mechanism underpins their efficacy in diseases such as multiple sclerosis (MS) and certain lymphomas but also predisposes patients to infections due to impaired humoral immunity (Chisari et al., 2022).
One of the most clinically significant infectious risks is HBV reactivation. Mastroianni et al. (2011) detailed that patients receiving anti-CD20 therapies are at substantial risk for HBV reactivation, which can lead to fulminant hepatitis and liver failure. This risk is particularly pronounced in patients with prior or occult HBV infection. Schluenz et al. (2019) demonstrated that compliance with protocol-driven HBV serological screening before initiation of anti-CD20 therapy significantly reduces reactivation rates by enabling timely antiviral prophylaxis.
Beyond viral reactivation, Tolaymat et al. (2026) conducted a scoping review highlighting an increased incidence of rhinosinusitis in adults receiving anti-CD20 therapy, often compounded by concurrent tumor necrosis factor alpha inhibitors. This suggests a broader susceptibility to bacterial infections of the upper respiratory tract, likely related to impaired B cell-mediated immune responses.
While anti-CD20 therapies have revolutionized treatment paradigms, their immunosuppressive effects necessitate a comprehensive infectious risk assessment. Shimada et al. (2018) emphasized the complexity of managing infections in patients with primary effusion lymphoma treated with anti-CD20 antibodies, underscoring the need for multidisciplinary care.
Caveats and uncertainty
The majority of evidence derives from observational studies, retrospective cohorts, and expert consensus rather than large randomized controlled trials specifically powered to evaluate infection risk stratified by anti-CD20 agents. Variability in patient populations, underlying diseases, and concomitant immunosuppressive therapies complicate risk attribution.
The optimal duration and choice of antiviral prophylaxis for HBV reactivation remain areas of ongoing research, with some uncertainty about management in patients with resolved HBV infection (HBsAg-negative, anti-HBc-positive). Additionally, the incidence and clinical impact of other opportunistic infections beyond HBV and rhinosinusitis are less well characterized.
Data on infection risk in emerging anti-CD20 agents beyond rituximab, such as obinutuzumab or ofatumumab, are limited, warranting cautious extrapolation. The evolving landscape of combination immunotherapies may further modify infection risk profiles.
How this may change practice
Clinicians initiating anti-CD20 monoclonal antibody therapy should implement standardized HBV screening protocols, including HBsAg, anti-HBc, and HBV DNA testing where indicated, to identify candidates for antiviral prophylaxis (Schluenz et al., 2019; Mastroianni et al., 2011). Prophylaxis should be maintained during and for an appropriate period after therapy completion.
Heightened clinical vigilance for bacterial infections such as rhinosinusitis is warranted, especially in patients receiving combination immunomodulatory treatments (Tolaymat et al., 2026). Early recognition and treatment of infections can prevent complications.
Multidisciplinary collaboration involving infectious disease specialists, hematologists, neurologists, and primary care providers is critical to optimize infection prevention and management strategies tailored to individual patient risks.
Ongoing education about infection risks associated with anti-CD20 therapies should be integrated into clinical practice guidelines and institutional protocols to improve patient outcomes.