Rituximab is an effective and safe therapeutic alternative in adults with refractory and severe autoimmune hemolytic anemia

Abstract

Rituximab-induced B cell depletion has been proven to be a useful therapy for autoimmune hemolytic anemia (AIHA). The aim of this retrospective study was to evaluate the effectiveness of rituximab in the treatment of 36 patients with AIHA refractory to several treatments. These patients had received a median of four (1-8) previous treatments, and 13 patients had undergone splenectomy. Rituximab was administered by intravenous infusion at a dose of 375 mg/m2 once weekly for 4 doses in 29 patients, and 7 patients received 1-6 doses. Overall, 28 of 36 patients (77%) achieved response. Twenty-two patients (61%) reached a complete response (CR), and 6 patients (16%) obtained a partial response (PR). All patients that reached CR (61%) were able to maintain the response during more than 6 months with a median follow-up of 14 months (1-86 months). Sixteen patients maintained response (Maintained Response; MR) for more than 1 year. The predictors of MR were achievement of CR and negative Coombs test result. Splenectomized patients showed a better response rate than those non-splenectomized. Rituximab was well tolerated, and only one patient presented a transitory rash during infusion. Rituximab induced clinical responses in multi-treated severe refractory both warm and cold AIHA patients with little toxicity and consequently, this therapy should be considered as an early therapeutic option in this setting.Response to Reviewers: In order to read the response to reviewers see attachment. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 2 AbstractRituximab-induced B cell depletion has been proven to be a useful therapy for autoimmune hemolytic anemia (AIHA). The aim of this retrospective study was to evaluate the effectiveness of rituximab in the treatment of 36 patients with AIHA refractory to several treatments. These patients had received a median of four (1-8) previous treatments, and 13 patients had undergone splenectomy.Rituximab was administered by intravenous infusion at a dose of 375 mg/m 2 once weekly for 4 doses in 29 patients, and 7 patients received 1-6 doses.Overall, 28 of 36 patients (77%) achieved response. Twenty-two patients (61%) reached a complete response (CR), and 6 patients (16%) obtained a partial response (PR). All patients that reached CR (61%) were able to maintain the response during more than 6 months with a median follow-up of 14 months (1-86 months). Sixteen patients maintained response (Maintained Response; MR) for more than 1 year. The predictors of MR were achievement of CR and negative Coombs test result. Splenectomized patients showed a better response rate than those non-splenectomized. Rituximab was well tolerated, and only one patient presented a transitory rash during infusion. Rituximab induced clinical responses in multi-treated severe refractory both warm and cold AIHA pati...

New autoimmune diseases after cord blood transplantation: a retrospective study of EUROCORD and the Autoimmune Disease Working Party of the European Group for Blood and Marrow Transplantation

“…2 Treatment of AIHA, ITP, and Evans syndrome was based on prednisone and RTX and CSA were most often used as immunosuppressive agents. Half of these patients needed second-line treatment and most responded to RTX, which was used in all but one patient as it has been shown to induce remissions of ITP 20 and AIHA 21 outside of the setting of HSCT. However, controlled data on the treatment for ADs after CBT are lacking, so more specific recommendations cannot be given at this stage.…”

Treatment of autoimmune hemolytic anemias

“…33 Rituximab has been shown to be effective both in idiopathic and secondary AIHA, including those associated with autoimmune and lymphoproliferative disorders, and bone marrow transplant. 31,32,[34][35][36][37] Responses to treatment were observed in monotherapy or in combination with corticosteroids, immunosuppressants and interferon-α, 35,36 and regardless of prior therapy. 34,35 The time to response varies considerably, with some patients responding very quickly and others taking weeks or even months to achieve their maximum response.…”

“…39 It is worth remembering that rituximab re-treatment may be effective 35,39,40 and some patients responded to re-treatment more than once. 34,35 Rituximab has also been found to be effective in Evans syndrome with a reported overall response of 83% (66% complete). 41 The response is even greater (up to 94%) considering the more recent and numerous series.…”

“…31,32,[34][35][36][37] Responses to treatment were observed in monotherapy or in combination with corticosteroids, immunosuppressants and interferon-α, 35,36 and regardless of prior therapy. 34,35 The time to response varies considerably, with some patients responding very quickly and others taking weeks or even months to achieve their maximum response. 35,38 In a recent multicenter retrospective study, the time to response was one month post-initiation of rituximab in 87.5% and three months in 12.5% of patients.…”

Rituximab in patients with refractory autoimmune hemolytic anemia

“…In their analysis the authors show that treatment with anti CD20 monoclonal antibodies is associated with an overall and complete response rate of 77% and 61% respectively [1]. As stated by Penalver et al most available evidence on the use of rituximab in AIHA is based on retrospective case reports and smaller case series, with only few uncontrolled prospective trials, which is mainly due to the rarity of the disorder.…”