Rituximab Use in Children
Rituximab can be used as a second-line treatment option for children with chronic refractory immune thrombocytopenia (ITP) with response rates between 31-68%, but should be reserved for those with significant ongoing bleeding despite first-line therapies. 1
Indications for Rituximab in Pediatric Patients
- Rituximab is indicated for children with chronic refractory ITP who have significant ongoing bleeding despite treatment with IVIg, anti-D, or conventional doses of corticosteroids (grade 2C) 1
- Rituximab may be considered as an alternative to splenectomy in children and adolescents with chronic ITP or in patients who do not respond favorably to splenectomy (grade 2C) 1
- Rituximab is FDA-approved for pediatric patients 2 years of age and older with Granulomatosis with Polyangiitis (GPA) and Microscopic Polyangiitis (MPA) 2
- Rituximab is FDA-approved for pediatric patients aged 6 months and older with previously untreated, advanced stage, CD20-positive DLBCL/BL/BLL/B-AL (diffuse large B-cell lymphoma/Burkitt lymphoma/Burkitt-like lymphoma/B-cell acute leukemia) 2
Dosing in Children
- For ITP: 375 mg/m² weekly for 4 doses 1, 3
- For GPA/MPA: 375 mg/m² once weekly for 4 weeks 2
- For CD20-positive DLBCL/BL/BLL/B-AL: in combination with chemotherapy as per protocols 2
Efficacy in Pediatric ITP
- Response rate (platelet count ≥50 × 10⁹/L) ranges between 31% and 68% in children with chronic refractory ITP 1
- Complete response (platelet count >150,000/mcL) has been reported in 63% of children with chronic ITP, with responses lasting 4-30 months 3
- Rituximab should be considered after failure of first-line therapies (IVIg, IV anti-D, short-course corticosteroids) 1
Safety and Adverse Events
- Infusion-related adverse events occur in approximately 15.4% of pediatric patients 4
- Anaphylaxis has been reported in 3.6% of pediatric patients 4
- Serum sickness can occur following rituximab administration 1, 3
- Infections occur in about 47.9% of pediatric patients receiving rituximab, with severe infections in 17.9% 4
- Risk factors for infection include:
- Transient severe acute thrombocytopenia and neutropenia may occur a few days after rituximab infusion 6
- Severe neutropenia (neutrophil count <500/mm³) has been reported in pediatric patients 7
- Hypogammaglobulinemia (IgG levels <500 mg/dL) can develop in pediatric patients 7
Immune Recovery After Rituximab
- CD19+ or CD20+ B-cell counts typically normalize in a median of 9.0 months (IQR 5.9-14.4 months) following rituximab use 4
- 51% of patients evaluated beyond one year still have low-for-age B-cell counts 4
- Recovery of CD27+ memory B-cell numbers occurs in a median of 15.7 months (IQR 6.0-22.7 months) 4
- Low immunoglobulin G (IgG) levels develop in 23.2% of patients with normal baseline values 4
- Low IgM levels develop in 40.8% of patients with normal baseline values 4
- Among patients evaluated beyond 12 months from rituximab, 13.7% have persistently low IgG and 33.9% have persistently low IgM 4
Monitoring Recommendations
- Monitor complete blood counts after rituximab infusion 6, 7
- Monitor immunoglobulin levels before and after treatment 4, 7
- Monitor for signs of infection during and after treatment 4, 5
- Monitor CD19+ B-cell counts to assess immune recovery 4, 7
Precautions and Contraindications
- Rituximab is not indicated in pediatric patients less than 2 years of age with GPA or MPA 2
- Rituximab has not been established as safe and effective in pediatric patients with chronic lymphocytic leukemia (CLL), pemphigus vulgaris (PV), or rheumatoid arthritis (RA) 2
- Verify pregnancy status in females of reproductive potential before initiating rituximab 2
- Advise females of reproductive potential to use effective contraception during treatment and for 12 months after the last dose 2
- Advise women not to breastfeed during treatment and for 6 months after the last dose 2