Why can Rituximab (rituximab) be administered subcutaneously (SQ) versus intravenously (IV) for certain indications?

Rituximab Subcutaneous vs. Intravenous Administration: Indications and Considerations

Rituximab can be administered subcutaneously (SC) only for specific indications, primarily follicular lymphoma and diffuse large B-cell lymphoma, after patients have tolerated at least one intravenous dose. The subcutaneous formulation is not approved for all indications that the intravenous formulation is used for.

Approved Indications for Subcutaneous Rituximab

Specific Conditions Where SC Administration is Approved:

• Follicular lymphoma (FL)
• Diffuse large B-cell lymphoma (DLBCL)

Key Administration Requirements:

• Patients must first receive at least one full dose of rituximab intravenously to assess tolerance 1
• SC rituximab is administered as a fixed dose of 1400 mg regardless of body surface area 2
• The first intravenous dose is typically 375 mg/m² 1

Evidence Supporting SC Administration

Patient Preference and Satisfaction:

• In the PrefMab study, 81% of patients with DLBCL or FL preferred subcutaneous over intravenous administration 2
• SC administration significantly reduces chair time for patients (minutes vs. hours for IV)
• Patient satisfaction as measured by the Rituximab Administration Satisfaction Questionnaire was higher for SC versus IV administration 2

Clinical Efficacy:

• A recent randomized trial showed that SC rituximab with short maintenance improved progression-free survival in low-tumor burden FL compared to standard IV rituximab (4-year PFS: 58.1% vs. 41.2%) 3
• Complete response rates were higher with SC rituximab (59.0% vs. 36.3%) 3

Indications Where SC Administration is NOT Approved

Rituximab SC is not approved for:

• Chronic lymphocytic leukemia (CLL) 1, 4
• Pemphigus vulgaris 1
• Acute lymphoblastic leukemia 1
• Other autoimmune conditions

Administration Protocol

Standard SC Administration:

1. First dose: Rituximab 375 mg/m² IV to assess tolerance
2. Subsequent doses: Rituximab 1400 mg SC fixed dose
3. For elderly vulnerable patients with follicular lymphoma, SC administration can be used after tolerating the first IV application 1

Special Considerations:

• SC administration is typically performed in the abdominal wall
• Administration time is approximately 5-7 minutes compared to several hours for IV infusion
• Patients should be monitored for at least 15 minutes following SC administration

Clinical Pearls and Pitfalls

Benefits of SC Administration:

• Reduced administration time
• Decreased healthcare resource utilization
• Improved patient convenience and satisfaction
• Fixed dosing simplifies preparation

Important Precautions:

• Always administer the first dose intravenously to monitor for infusion reactions
• Hepatitis B testing is required before initiating rituximab regardless of administration route 1
• Anti-infective prophylaxis considerations remain the same for both routes of administration
• SC administration is contraindicated in patients who experienced severe reactions to IV rituximab

Conclusion

Subcutaneous rituximab offers a convenient alternative to intravenous administration for specific lymphoma indications (FL and DLBCL) after patients have demonstrated tolerance to at least one IV dose. The evidence shows high patient preference and satisfaction with SC administration without compromising efficacy. For other indications such as CLL, pemphigus vulgaris, and other conditions, the intravenous formulation remains the only approved administration route.