High dose Rituximab (anti-cd20 monoclonal antibody) in children with chronic refractory immune
thrombocytopenic purpura: efficacy and safety of treatment, single center experience
(preliminary result)
Mohammad O. Olfat, MD, Ahmad M. Tarawah, MD Maternity and Children Hospital, King Abdullah Medical City
Madinah, Saudi Arabia
Immune Thrombocytopenic Purpura (ITP)
• Incidence 2.3 – 5.3 X105
• Chronic ITP (> 12 months) 20 %
First-line management Second-line therapy
Prednisone Rituximab Splenectomy
HD Dexamethasone TPO-RA Cyclophosphamide
Immunoglobulin Cyclosporine Azathioprine
Anti-D immunoglobulin Vincristine
Danazol
Hydroxychloroquine
Mycophenolate Mofetil
Terrell, Deirdra R., et al. American journal of hematology 85.3 (2010): 174-180. Lambert, Michele P., and Terry B. Gernsheimer. Blood 129.21 (2017): 2829-2835.
Rituximab
• McLaughlin, Peter, et al. "Rituximab chimeric anti-CD20 monoclonal antibody therapy for relapsed indolent lymphoma: half of patients respond to a four-dose treatment program." Journal of clinical oncology 16.8 (1998): 2825-2833.
• Van Der Kolk, Le, et al. "Chimeric Anti-cd20 Monoclonal Antibody (rituximab) Plus G-csf In Relapsed B-cell Lymphoma." British Journal of Haematology 102
• Saleh, Mansoor N., et al. "A pilot study of the anti-CD20 monoclonal antibody rituximab in patients
with refractory immune thrombocytopenia." Seminars in oncology. Vol. 27. No. 6 Suppl 12. 2000.
• Zaja, Francesco, et al. "Earlier administration of rituximab allows higher rate of long-lasting response in adult patients with autoimmune thrombocytopenia." Experimental hematology 34.5 (2006): 571-572.
• Patel, Vivek L., et al. "Outcomes 5 years after response to rituximab therapy in children and adults with immune thrombocytopenia." Blood 119.25 (2012): 5989-5995.
• Gudbrandsdottir, Sif, et al. "Effects of rituximab and dexamethasone on regulatory and proinflammatory B‐cell subsets in patients with primary immune thrombocytopenia." European journal of haematology 100.1 (2018): 45-52.
Rituximab
• Rituximab is a chimeric, monoclonal anti-CD20 antibody that targets B lymphocytes and causes Fc-mediated cell lysis
liver sections of a tumor Rituximab treated mouse injected untreated mouse Di Gaetano, Nicola, et al. The Journal of Immunology 171.3 (2003): 1581-1587.
Platelet response to rituximab
Arnold, Donald M., et al. Annals of internal medicine 146.1 (2007): 25-33.
Roberto Stasi et al. Blood 2001;98:952-957
• 18 studies
• 352 patients (0.5 to 19 years old)
• Doses of rituximab • 375 mg/m2/week for 1∼6 dose escalation to 750 mg/m2/dose
• 100 mg/dose/week for 4 doses
• 500 mg/m2/dose every 2 weeks for 2 doses
• Response • Response (platelet count ≥30×109 /L) 68%
• Complete response (platelet count ≥100×109 /L) 39%
• Time to response 0.3 to 17.0 weeks Liang, Yi, et al PloS one 7.5 (2012): e36698.
Rituximab plus standard of care for treatment of primary immune thrombocytopenia: a systematic review and meta-analysis
Chugh, Shaan, et alThe Lancet Haematology 2.2 (2015): e75-e81.
Complete response Partial response reduction in bleeding increase in infections
32.5
46.7
5.2
12.1
46.5
57.6
9.2
20.1
standard of care rituximab
P= 0·0020 P= 0·11 P= 0·44 P= 0·17
Outcomes 5 years after response to rituximab
therapy in children and adults with immune
thrombocytopenia
Vivek L. Patel et al. Blood 2012;119:5989-5995
High dose Rituximab (anti-cd20 monoclonal antibody) in children with chronic refractory immune thrombocytopenic purpura: efficacy and safety of treatment, single center experience (preliminary result)
High dose Rituximab (anti-cd20 monoclonal antibody) in children with chronic refractory immune thrombocytopenic purpura: efficacy and safety of treatment, single center experience (preliminary result)
METHODS
• Single arm, single center, open label prospective study.
• Study has been opened on June 2015 – on going. • Children 2-14 years
• Chronic refractory ITP.
• Rituximab (anti-CD20) 500 mg/m2 IV on day 1 and day15.
• Course can be repeated after 13 weeks if no response after first course.
High dose Rituximab (anti-cd20 monoclonal antibody) in children with chronic refractory immune thrombocytopenic purpura: efficacy and safety of treatment, single center experience (preliminary result)
RESULTS
• 8 patients
• 5 girls and 3 boys.
• Current median age is 9.8 years (4.7-14)
• Median age at diagnosis was 6.4 years (1.2-8.5).
• All subjects have shown unsuccessful or non-persistent response to oral prednisolone at dose of 2m/kg.
• Splenectomy performed in one patient
High dose Rituximab (anti-cd20 monoclonal antibody) in children with chronic refractory immune thrombocytopenic purpura: efficacy and safety of treatment, single center experience (preliminary result)
• RESULTS
6 Months Rituximab
50
100
200
300
High dose Rituximab (anti-cd20 monoclonal antibody) in children with chronic refractory immune thrombocytopenic purpura: efficacy and safety of treatment, single center experience (preliminary result)
• RESULTS
6 Months 12 Months Rituximab
50
100
200
300
High dose Rituximab (anti-cd20 monoclonal antibody) in children with chronic refractory immune thrombocytopenic purpura: efficacy and safety of treatment, single center experience (preliminary result)
• RESULTS
6 Months 12 Months 18 Months 24 Months Rituximab
50
100
200
300
High dose Rituximab (anti-cd20 monoclonal antibody) in children with chronic refractory immune thrombocytopenic purpura: efficacy and safety of treatment, single center experience (preliminary result)
RESULTS
• Adverse effects
• Leukopenia 1
• Major infection 0
• Recurrent infection 0
• Other side effects 0
High dose Rituximab (anti-cd20 monoclonal antibody) in children with chronic refractory immune thrombocytopenic purpura: efficacy and safety of treatment, single center experience (preliminary result)
CONCLUSION
High dose Rituximab (anti-cd20 monoclonal antibody) in children with chronic refractory immune thrombocytopenic purpura: efficacy and safety of treatment, single center experience (preliminary result)
8th PAN-ARAB HEMATOLOGY CONGRESS
MADINAH, SAUDI ARABIA
FEBRUARY 16-18, 2019