The Use of Anti-CD20 Chimeric Monoclonal Antibody, Rituximab in Adult Patients with Treatment Refractory Immune Thrombocytopenia.

Introduction: Approximately 20–30% of treated patients with immune thrombocytopenia (IT) will become resistant to standard therapy. Rituximab has been reported to be effective in nearly 50% of such patients. The following report describes our experience using rituximab as both a splenectomy-sparing and salvage intervention in a heterogenous group of IT patients.

Patients and Methods: 11 patients were evaluated retrospectively. Their characteristics were as follows: median age of 44 (range 20–79); 6 were female; median IT duration was 2.8 yrs (range 1mo-17yrs); median number of prior treatments was 3 (range 1–8); all patients had received steroids and most, high dose immunoglobulin. Other treatments included anti-RhD, vincristine, danazol, cyclophosphamide, staphylococcal protein-A column, plasmapheresis, mycophenolate mofetil, cyclosporine and autologous stem cell transplantation (ASCT). 6 patients (55%) had been splenectomized. 8 patients had primary idiopathic thrombocytopenic purpura (ITP) including 2 cases of Evan’s syndrome (ES) and 3 had secondary IT associated with antiphospholipid antibody syndrome (APS), cutaneous panniculitis-like T-cell lymphoma and chronic lymphocytic leukemia (CLL). The planned treatment was rituximab 375 mg/m2 i.v. weekly x 4. A complete response (CR) was defined as a rise in platelet count >100 X 10⁹/L for greater than 3 months, partial response (PR) was defined as a rise in platelet count >50 X 10⁹/L and no response (NR) was defined as no change or a rise < 50 X10⁹/L.

Results: All patients received the 4 doses of rituximab except 1 patient who achieved CR after 1 dose. Of the 8 primary ITP patients 6 (75%) attained CR, 1 had a transient PR and 1 a NR. All 3 patients with secondary IT reached CR. Overall, 91% of patients responded and 81% had CR. 1 ITP patient was spared a splenectomy and remains in CR at 7 mos. 5 of 6 (83%) splenectomized ITP patients reached CR and the 6^th had a brief PR and failed to respond to retreatment. 4 of 5 splenectomized patients remain in CR at 3, 3, 32 and 34 mos, respectively. The last patient is a 44 y/o M with ES for 17 yrs who attained a transient CR with stable hemolysis but relapsed and was retreated 6 mos later with a sustained CR for nearly 3 years while maintained on intermittent rituximab therapy. Notably, he has experienced hypogammaglobulinemia with recurrent pneumonia. The 5^th splenectomized patient reaching CR was a 35 y/o M with ES refractory to extensive pretreatment including ASCT and had a transient PR only after rituximab. He was retreated 4 mos later and reached a sustained CR 3 mos from last dose but died from hepatic failure characterized by marked cholestasis with loss of bile ducts of unclear etiology but possibly drug related. Among those with secondary IT is a 27 y/o F with APS who responded after 1 rituximab dose and remains in CR at 12 mos. Both cases of CLL and T-cell lymphoma remain untreated for their primary disease and continue in CR at 6 and 22 mos, respectively. No characteristic predicting response was identified. Rituximab therapy was well tolerated with limited infusional reaction, fatigue and headache occurring in 3 of 10 patients.

Conclusion: In contrast to published reports, 81% of our refractory IT patients treated with rituximab had durable responses. Furthermore, it appears retreatment and maintenance therapy may be effective in refractory IT at the expense of possibly an increased risk for infection.