Should rituximab (Rituxan) be repeated?

Repeating Rituximab: Indications and Recommendations

Rituximab should be repeated based on clinical relapse rather than administered on a fixed schedule, with the exception of specific protocols for certain conditions that require maintenance therapy. 1

Disease-Specific Recommendations for Rituximab Retreatment

For Lymphomas:

• Diffuse Large B-Cell Lymphoma (DLBCL):

  • Initial treatment: 6-8 cycles of R-CHOP with 8 doses of rituximab given every 21 days 1
  • Retreatment: Only upon relapse/progression with second-line chemotherapy 1
  • No evidence supports maintenance rituximab in DLBCL

• Lymphocyte-Predominant Hodgkin Lymphoma (LPHL):

  • Maintenance rituximab for 2 years may be considered for patients initially treated with rituximab alone 1
  • However, more recent data suggests maintenance may not significantly increase PFS compared to rituximab alone (67 vs 50 months) 1

• Follicular Lymphoma:

  • For elderly patients with high tumor burden: Consider rituximab maintenance after initial remission 1
  • For relapsed disease with long remission duration (>18-24 months): The initial rituximab/chemotherapy regimen can be repeated 1
  • For shorter remission: Use alternate rituximab/chemotherapy combinations 1

For Autoimmune Conditions:

• Membranous Nephropathy:

  • Retreatment should be considered when patients relapse after initial response 1
  • Patients who initially responded to rituximab have similar outcomes when retreated 1

• Steroid-Dependent Nephrotic Syndrome:

  • Repeated courses of rituximab can achieve long-term remission in 69% of patients 2
  • Time to relapse is significantly longer with 3-4 initial infusions compared to 1-2 infusions 2

• Primary Sjögren Syndrome:

  • Retreatment upon clinical relapse shows 65% response rate in second cycle 3
  • Be aware that 17% of patients develop secondary non-depletion and non-response (2NDNR) 3

Factors Affecting Successful Retreatment

1. Complete B-cell depletion: Achieving complete B-cell depletion in first cycle increases odds of response to subsequent rituximab cycles (OR 9.78) 3

2. Concomitant immunosuppression: Co-prescription of immunosuppressants with rituximab increases odds of response (OR 7.16) 3

3. Timing of retreatment:

   • For most conditions: Retreat upon clinical relapse rather than fixed schedule 4
   • For vaccinations: Time vaccination for when next rituximab dose is due, then hold rituximab for at least 2 weeks after vaccination 1

Important Considerations and Cautions

• Monitor for infusion reactions: Most common adverse effect (up to 77% during first infusion) 5

  • Premedicate with diphenhydramine, acetaminophen, and corticosteroids
  • Use gradual infusion and close monitoring

• Infection risk: Occurs in approximately 31% of patients on R-CHOP 5

  • Consider prophylactic antibiotics for high-risk patients
  • Monitor for hepatitis B reactivation in HBsAg or anti-HBc positive patients

• Secondary non-response: About 1 in 6 patients may develop secondary non-depletion and non-response in repeat cycles 3

• Alternative approaches: For patients who fail to respond to repeated rituximab, consider alternative immunosuppressants or combination therapy 6

Conclusion

The decision to repeat rituximab should be based primarily on clinical relapse rather than fixed schedules, except in specific protocols requiring maintenance therapy. Complete B-cell depletion and concomitant immunosuppression improve the likelihood of sustained response to repeated rituximab cycles. Monitor closely for infusion reactions and infections with each retreatment.