high dose rituximab (anti-cd20 monoclonal antibody) in...

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)


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.


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


• RESULTS

6 Months Rituximab

50

100

200

300


• RESULTS

6 Months 12 Months Rituximab

50

100

200

300


• RESULTS

6 Months 12 Months 18 Months 24 Months Rituximab

50

100

200

300


RESULTS

• Adverse effects

• Leukopenia 1

• Major infection 0

• Recurrent infection 0

• Other side effects 0


CONCLUSION


8th PAN-ARAB HEMATOLOGY CONGRESS

MADINAH, SAUDI ARABIA

FEBRUARY 16-18, 2019

high dose rituximab (anti-cd20 monoclonal antibody) in...

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