Maintenance rituximab for relapsing thrombotic thrombocytopenic purpura: a case report

Abstract

BACKGROUND Appropriate management to prevent relapses of acquired, autoimmune thrombotic thrombocytopenic purpura (TTP) is not clear. Rituximab (375 mg/m2/week × 4) is effective treatment for acute episodes but it is not consistently effective for prevention of relapses. Maintenance rituximab, 375 mg/m2/3 months for 2 years, is commonly used to prevent progression of follicular lymphoma, but the outcome of maintenance rituximab to prevent TTP relapses has been rarely reported. CASE REPORT An 8‐year‐old girl was diagnosed with acquired TTP in 2008; her ADAMTS13 activity was less than 5%, with a functional inhibitor of greater than 8 Bethesda units/mL. She achieved remission with therapeutic plasma exchange, corticosteroids, and rituximab (375 mg/m2/week × 4). During the following 6 years she had seven additional episodes. Each episode responded to therapeutic plasma exchange, sometimes requiring additional treatments (corticosteroids, rituximab, and cyclophosphamide). However, these treatments, as well as splenectomy and trials of cyclophosphamide and mycophenolate mofetil during clinical remissions, failed to prevent relapses. Her ADAMTS13 activity remained 8% or less throughout all of her remissions. Maintenance rituximab was begun in 2013: 500 mg (313 mg/m2) every 2–3 months × 5, then 600 mg (375 mg/m2) every 6 months × 2. After 1 year, her ADAMTS13 was 26%; after 2 years, 51%. During the past 3 years since stopping rituximab, she has remained well, with normal ADAMTS13 activity (70%–78%). CONCLUSION Maintenance rituximab treatment may be effective for prevention of relapses in patients with acquired, autoimmune TTP, even when splenectomy and intensive immunosuppression, including multiple conventional courses of rituximab, fail to prevent subsequent relapses.

Refractory thrombotic thrombocytopenic purpura related to checkpoint inhibitor immunotherapy

“…While reports of sustained response following multiple initial TTP relapses have been reported when sustained intervention with rituximab therapy has been employed, 25 an altered course of auto reactive B‐lymphocyte development and plasma cell formation may result in plasma cells that continue to produce anti‐ADAMTS13 autoantibodies after TPE that may be refractory to anti‐CD20 therapy. In this setting, while anti‐ADAMTS13 may initially decrease with the use of rituximab due to inhibition of B‐lymphocyte differentiation into antibody‐secreting cells, such as short‐lived plasmablasts, 26 persisting long‐lived CD20‐negative plasma cells that form as a result of an enhanced TFH response may continue to produce autoantibodies that contribute to delays in achieving increased levels of ADAMTS13 activity 24 .…”

Thrombotic Thrombocytopenic Purpura: When Basic Science Meets Clinical Research

“…In these cases, a more intensive regimen inspired from those used in lymphoid malignancies and consisting of 4 to 6 weekly infusions and/or maintenance treatment (4 infusions/year for 2 years) may overcome rituximab refractoriness. 59,60 Recently, subcutaneous preemptive rituximab was shown to have similar efficacy than IV perfusion as a preemptive treatment for iTTP and could ease the management of these patients, notably when repeated administrations are needed, by decreasing the burden of care and improving patients' satisfaction. Therefore, subcutaneous rituximab could represent a new standard of care in the prevention of iTTP relapses.…”

Immune-Mediated Thrombotic Thrombocytopenic Purpura: A Narrative Review of Diagnosis and Treatment in Adults

“…10 mg IV followed by 10 mg SC daily Consider early use in patients with high-risk disease and timely access to ADAMTS13 testing. Case reports of complete remission in patients with multirefractory iTTP [76][77][78][79] Splenectomy Consider in the nonacute period of primary refractory or multiply relapsed iTTP when other options have been exhausted 10-year RFS of 70% (95% CI: 50-83%); relapse rate reduced from 0.74/year to 0.1 relapse/year 92 Prevention of relapses Rituximab Available evidence supports pre-emptive rituximab when ADAMTS13 activity becomes <10% [82][83][84][85][86][87] To prevent one relapse NNT 1.6 67 To prevent one death NNT 32 67 Abbreviations: ADAMTS13, a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13; CR, complete remission; CSA, cyclosporine; iTTP, immune TTP; IV, intravenously; NNT, number needed to treat; PEX, plasma exchange; PO, orally; RFS, relapse-free survival; TTP, thrombotic thrombocytopenic purpura.…”

“…There is mounting evidence in support of pre-emptive rituximab to prevent relapses in patients in clinical remission when ADAMTS13 activity becomes undetectable (< 10%). [82][83][84][85][86][87] It remains unclear which is the superior strategy for reducing the rate of disease relapse: upfront treatment with rituximab in the acute phase versus prophylactic administration in remission if declining or persistently low ADAMTS13 levels. Finally, while the introduction of rituximab has been a significant breakthrough in iTTP management leading to shorter response time, fewer and later relapses, it did not affect early deaths within the first 10 days of diagnosis.…”