What Are the Side Effects of Rituximab Maintenance?

You will not have to stay on rituximab maintenance forever. Standard maintenance therapy for follicular lymphoma is typically given for up to two years ^[1][2]. Its primary purpose is to keep your disease in remission longer. However, because it continuously suppresses a part of your immune system, it carries risks such as increased susceptibility to infections, low antibody levels (hypogammaglobulinemia), and late drops in white blood cell counts (late-onset neutropenia) ^[1][3].

The Goal, Timeline, and Logistics of Maintenance Therapy

After you successfully complete your initial treatment (induction therapy) and your lymphoma is in remission, your doctor may recommend rituximab maintenance. While being in remission is wonderful news, acknowledging that you still have to visit the cancer center regularly for two years can feel like a heavy emotional and logistical burden.

• Duration: It is generally administered once every 8 weeks for up to two years ^[1].
• Administration: Maintenance can be given as a traditional intravenous (IV) infusion at the cancer center or, in some cases, as a much faster subcutaneous injection (a shot under the skin), which significantly shortens your time in the clinic ^[4][5].
• Purpose: The goal is to extend your progression-free survival—the length of time you live without the disease returning or worsening. Studies show that two years of maintenance significantly delays the need for further chemotherapy ^[1][6].
• Overall Survival: While it keeps the lymphoma away longer, studies show that patients who receive maintenance live roughly the same total amount of time as those who do not (overall survival) ^[1].

Because it does not extend your total lifespan, the decision to complete the full two years of maintenance is a balance between enjoying a longer remission and managing the side effects of prolonged immune suppression.

Key Side Effects to Watch For

Rituximab works by targeting and depleting B-cells, a type of white blood cell involved in your lymphoma. However, because healthy B-cells are responsible for producing immunoglobulins (antibodies) that fight off illnesses, depleting them leaves your immune system compromised ^[7][3].

Increased Risk of Infections

The most common side effect of extended rituximab use is a higher risk of infections, such as colds, sinus infections, or bronchitis ^[8][9]. Your care team will monitor you closely, and you should report any signs of infection (like a fever, cough, or sore throat) immediately.

Hypogammaglobulinemia (Low Antibodies)

Because rituximab keeps your B-cell count low for two years, your overall antibody levels can drop, a condition called hypogammaglobulinemia ^[7].

• This makes it harder for your body to fight off recurrent infections.
• Your doctor can check your immunoglobulin levels through a simple blood draw (often done right before your maintenance infusion).
• If your levels become dangerously low and you are getting frequent infections, your doctor might recommend stopping the rituximab or giving you immunoglobulin replacement therapy (IgRT) to temporarily boost your antibodies ^[10][11].

Late-Onset Neutropenia

Neutrophils are a different type of white blood cell that acts as a first responder to bacterial infections. Late-onset neutropenia is a sudden drop in these cells that can happen months after you start or even finish rituximab therapy ^[12][3].

• It happens in roughly 6% of patients receiving this treatment ^[12].
• Often, it causes no symptoms and resolves on its own without needing specific treatment ^[13][14].
• Because low neutrophils leave you vulnerable to severe infections, your care team will continue monitoring your complete blood counts (CBC) throughout your maintenance period, typically via a blood draw before each treatment ^[15].

Reduced Vaccine Effectiveness

Because your B-cells are depleted and cannot efficiently produce antibodies, standard vaccines (like the flu, COVID-19, or RSV vaccines) will not work as well while you are on maintenance therapy ^[16][17]. Although your immune system may still mount a partial defense using other immune cells, you should consult your care team about the optimal timing for vaccines. Furthermore, you must avoid “live” vaccines (like the yellow fever or oral polio vaccines) while you are immunocompromised.

Daily Precautions

While on maintenance therapy, taking practical steps can help you live safely:

• Avoid sick contacts: Steer clear of crowds and people who are visibly ill.
• Practice good hygiene: Wash hands frequently and carry hand sanitizer.
• Masking: Consider wearing a high-quality mask (like an N95) when in crowded indoor spaces or during peak cold and flu seasons.
• Food safety: Ensure your food is properly cooked and avoid unpasteurized dairy products to minimize exposure to foodborne bacteria.

If the side effects, emotional toll, or infection risks ever outweigh the benefits, you and your doctor can decide to stop maintenance therapy early.