What is the dosing regimen for Rituximab (rituximab) as part of a desensitization protocol for a kidney transplant workup patient with positive Donor-Specific Antibodies (DSA)?

Rituximab Dosing Regimen for Desensitization in Kidney Transplant Patients with Positive DSA

The recommended dosing regimen for rituximab as part of a desensitization protocol for kidney transplant patients with positive donor-specific antibodies (DSA) is 375 mg/m² IV, typically administered as a single dose or two doses separated by 1-2 weeks. 1

Desensitization Protocol Components

• Rituximab is most effective when used as part of a comprehensive desensitization protocol that includes plasmapheresis and intravenous immunoglobulin (IVIG) 2
• A typical desensitization protocol for kidney transplant candidates with positive DSA includes:
  • Plasmapheresis: 5-6 sessions over 10-14 days 1
  • IVIG: 2 g/kg divided into doses (often administered after plasmapheresis) 1, 3
  • Rituximab: 375 mg/m² IV, typically as a single dose or two doses of 1g (375 mg/m² for smaller patients) 1, 4

Timing Considerations

• Rituximab is most commonly administered:
  • As a single dose at the beginning of the desensitization protocol 5
  • Or as two doses on days 7 and 21 of the protocol 1
  • Some centers administer rituximab on day 8 after transplantation when used in deceased donor protocols 3

Monitoring and Response Assessment

• Monitor DSA levels before and after desensitization to assess efficacy 5, 4
• Successful desensitization typically results in:
  • Reduction in DSA mean fluorescence intensity (MFI) by approximately 46% at 1 month post-transplant 4
  • Complete response (MFI <1000) in approximately 62% of patients 4
  • Partial response (MFI reduced but >1000) in an additional 31% of patients 4

Advanced Protocols for Highly Sensitized Patients

• For highly sensitized patients who fail to respond to conventional desensitization:
  • Consider a phased approach with rituximab followed by bortezomib 6
  • Administer rituximab first, then monitor for reappearance of naive B cells while memory B cells remain undetectable 6
  • When naive B cells reappear, administer one cycle of bortezomib (1.3 mg/m² on days 1,4,8, and 11) followed by plasmapheresis 1, 6

Premedication and Adverse Effect Management

• Premedicate with:
  • Diphenhydramine 25-50 mg 7
  • Acetaminophen 650 mg 7
  • Methylprednisolone 40 mg IV (for moderate to severe reactions) 7
• Common adverse effects include:
  • Infusion reactions (up to 20% with first infusion) 7
  • Cytokine release syndrome 7
  • Gastrointestinal side effects 7

Efficacy and Outcomes

• Rituximab as part of desensitization protocols has demonstrated:
  • Significant reduction in DSA levels that can be sustained for up to 3 years post-transplant 4
  • Reduced incidence and magnitude of HLA antibody rebound post-transplant 5
  • Excellent 3-year patient and graft survival rates (95% and 90%, respectively) 4
  • Low incidence of acute rejection (approximately 14%) 4

Important Considerations and Caveats

• Rituximab appears more effective at preventing new antibody formation than eliminating existing DSAs 5
• Memory B cells may be less effectively depleted, particularly those specific to previous allografts or pregnancies 5
• Screening for hepatitis B infection before initiating rituximab is essential to prevent viral reactivation 7
• Consider adding bortezomib to the protocol for patients with persistent high-level DSAs despite rituximab, plasmapheresis, and IVIG 8, 6