Lower dose rituximab is active in adults patients with idiopathic thrombocytopenic purpura

Zaja, Francesco; Battista, Marta Lisa; Pirrotta, Maria Teresa; Palmieri, Salvatore; Montagna, Michela; Vianelli, Nicola; Marin, Luciana; Cavallin, Margherita; Bocchia, Monica; Defina, Marzia; Ippoliti, Micaela; Ferrara, Felicetto; Patriarca, Francesca; Avanzini, Maria Antonietta; Regazzi, Mario; Baccarani, Michele; Isola, Miriam; Soldano, Franca; Fanin, Renato

doi:10.3324/haematol.12206

Cited by 92 publications

(75 citation statements)

References 20 publications

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“…In one small series sustained complete response was achieved in four of 7 patients (57%) and no infusion reactions were seen [59]. In a slightly larger series overall and complete responses were achieved in 21/28 (75%) and 12/28 (43%) patients respectively [60]. Further studies are warranted to confirm these preliminary data, as a lower dose may be associated with a lower risk of toxicities.…”

Section: Rituximabsupporting

confidence: 55%

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Should medical treatment options be exhausted before splenectomy is performed in adult ITP patients? A debate

et al. 2010

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Patients with primary immune thrombocytopenia (ITP) may require treatment to reduce the risk of serious bleeding if platelets remain consistently below 30 x 109/L. While approximately 70-80% of patients respond to an initial course of corticosteroids, relapse is common. For steroid-refractory patients, there is a choice between surgical splenectomy and further medical treatments, based on many factors including the patient's bleeding history, fitness for surgery, comorbidities, tolerance of adverse events, lifestyle and preferences. Treatments that have traditionally been used (corticosteroids, azathioprine, danazol) suppress the immune system, potentially predisposing patients to infection. Recent insights into the underlying pathophysiology of the disease have allowed the development of targeted therapies, including the thrombopoietin (TPO) receptor agonists, which enhance platelet production. Phase III trials have found romiplostim and eltrombopag to be well tolerated and effective in elevating platelet counts and reducing bleeding in both splenectomised and nonsplenectomised patients with chronic ITP. The B-cell targeted monoclonal antibody rituximab has also shown some potential in this setting, although data are currently limited and there are toxicity concerns. The decision whether to proceed to splenectomy or try other medical therapies in corticosteroidrefractory patients remains patient-specific. Splenectomy has its risks (including perioperative and long-term risks), and relapse/nonresponse are relatively common, but it offers the possibility of cure in the majority of patients. However, newer treatments may potentially allow splenectomy to be deferred for prolonged periods, as well as providing alternative treatment options for patients who fail splenectomy . 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 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 However, newer treatments may potentially allow splenectomy to be deferred for prolonged periods, as well as providing alternative treatment options for patients who fail splenectomy.

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Section: Rituximabsupporting

confidence: 55%

“…A low-dose rituximab regimen (100mg weekly for 4 consecutive weeks) has been explored in ITP patients, with encouraging results [59,60]. In one small series sustained complete response was achieved in four of 7 patients (57%) and no infusion reactions were seen [59].…”

Section: Rituximabmentioning

confidence: 99%

Should medical treatment options be exhausted before splenectomy is performed in adult ITP patients? A debate

et al. 2010

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“…Additional mechanisms of action have been proposed, including the indirect modulation of T-cell homeostasis [7]. Three noncontrolled studies have reported the efficacy of RTX given at lower doses (100 mg every week for 4 weeks), and have shown good short-term response rates [8][9][10]. In rheumatoid arthritis (RA), RTX has been licensed at a fixed dose (1,000 mg on days 1 and 2), though this arbitrary regimen was chosen by the manufacturer in both phase II and III trials [11].…”

Section: Introductionmentioning

confidence: 99%

Efficacy and safety of rituximab given at 1,000 mg on days 1 and 15 compared to the standard regimen to treat adult immune thrombocytopenia

Mahévas

Ebbo

Audia³

et al. 2013

American J Hematol

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Rituximab (RTX) is used off-label to treat immune thrombocytopenia (ITP) but the regimen now commonly used in rheumatoid arthritis has not been evaluated in ITP. The aim of this large French multicenter retrospective study was to compare the efficacy and safety of two RTX regimens in adult's ITP. The efficacy of two (RTX) regimens: standard therapy of 375 mg/m 2 weekly for 4 weeks vs. a rheumatoid arthritis (RA) regimen of 1,000 mg on days 1 and 15, to treat ITP was compared. We included adults patients with previously primary ITP treated with RTX instead of treated primary ITP. (CR) was defined as a platelet count >100 3 10 9 /L, and a response (R) by a platelet count of >30 3 10 9 /L with a least a doubling of the baseline value. Of the 107 patients included, 61 (57%) received the standard regimen and 46 (43%) the RA regimen. Baseline characteristics and overall response rates at 3 month (M3) and 12 months (M12) were not significantly different between the groups. At M12, 22/61 patients (36%) treated with the standard regimen and 23/46 (50%) with the RA regimen achieved an overall response (R 1 CR). The initial pattern of response at M3 was associated with a later pattern of response by M12 in both groups. In multivariate analysis, both a younger age and a low number of previous therapies were associated with a higher likelihood of overall response at M12. Tolerance was good and comparable between the two groups. The RA regimen is an effective and safe alternative to the standard regimen to treat adults with ITP. Am. J. Hematol. 88:858-861,

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“…Regarding the effectiveness of low-dose RTX, possible mechanisms may involve the small amount of abnormally activated B-lymphocytes in TTP, as opposed to clonal B-lymphocytes in malignant lymphoma; thus, a lower RTX dose may eliminate the abnormally activated B-lymphocytes. In addition, certain studies have demonstrated that after the first week of RTX treatment, peripheral blood CD20 + cells had almost disappeared in ITP patients (15,16). Therefore, for autoimmune diseases, the current authors hypothesized that RTX may not require a dose as large as that used in B-cell lymphoma.…”

Section: Discussionmentioning

confidence: 99%

Long-term remission induced by low-dose rituximab for relapsed and refractory thrombotic thrombocytopenic purpura: A report of two cases

Tong¹,

Li²,

Ye³

et al. 2015

Experimental and Therapeutic Medicine

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Abstract. Thrombotic thrombocytopenic purpura (TTP) is acquired in the majority of cases. Traditional therapy consists of plasma exchange (PEX), as well as the administration of certain immunosuppressive agents including steroids. A standard dose of rituximab (RTX) at 375 mg/m 2 weekly for 4 consecutive weeks was recently demonstrated to have significant activity in patients with acquired TTP. To date, clinicians have limited experience using low-dose RTX. In the present study, 2 patients were treated with low-dose RTX at 100 mg weekly for 4 consecutive weeks as a salvage therapy following failure to respond to PEX and other immunosuppressive agents. Prior to RTX therapy, the patients had severely deficient ADAMTS13 activity and detectable anti-ADAMTS13 inhibitors. The patients achieved complete remission and presented long-term stabilization during follow-up. Repeated detection during follow-up demonstrated that the patients had 100% ADAMTS13 activity and undetectable anti-ADAMTS13 antibodies. Although further investigation in a prospective clinical trial is required, the use of low-dose RTX seems to be as effective as a standard dose for patients with relapsing or refractory acquired

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Lower dose rituximab is active in adults patients with idiopathic thrombocytopenic purpura

Cited by 92 publications

References 20 publications

Should medical treatment options be exhausted before splenectomy is performed in adult ITP patients? A debate

Should medical treatment options be exhausted before splenectomy is performed in adult ITP patients? A debate

Efficacy and safety of rituximab given at 1,000 mg on days 1 and 15 compared to the standard regimen to treat adult immune thrombocytopenia

Long-term remission induced by low-dose rituximab for relapsed and refractory thrombotic thrombocytopenic purpura: A report of two cases

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