Ofatumumab for acute treatment and prophylaxis of a patient with multiple relapses of acquired thrombotic thrombocytopenic purpura

Abstract

Acquired thrombotic thrombocytopenic purpura (TTP) is an autoimmune disorder resulting in potentially life-threating systemic thrombotic microangiopathy due to production of antibodies directed against the von Willebrand factor-cleaving protease ADAMTS13. Typically managed with plasma exchange, glucocorticoids, and the first-generation anti-CD20 monoclonal antibody rituximab, patients with multiple relapses or refractory disease present unique management challenges. We describe a case of a young woman with multiple relapses of TTP despite standard therapy who was treated with ofatumumab, a second-generation anti-CD20 monoclonal antibody, after developing a severe hypersensitivity reaction to rituximab precluding its use. Ofatumumab was effective for the treatment of an acute relapse of TTP in combination with plasmapheresis and as a single-agent for prophylaxis. The patient has had no evidence of relapse 2 years after completion of acute treatment and 1 year after completing prophylactic therapy. Hypersensitivity to ofatumumab did not develop.

Expert statement on the ICU management of patients with thrombotic thrombocytopenic purpura

“…As stated above, we suggest caplacizumab as a first line agent in all severe TTP patients, especially with a high and prolonged risk of thromboembolic events and sudden death 17,103 . In case of failure of rituximab, ofatumumab might be an option 109 . It has also been suggested that in patients unresponsive to treatment, centrifugation devices might be preferred over plasma filters (lower shear stress rates).…”

The use of obinutuzumab and ofatumumab in the treatment of immune thrombotic thrombocytopenic purpura

“…The former is also currently licensed for the use in relapsing multiple sclerosis 13,15 . Case reports of the successful use of both mAbs leading to disease remission have been described by ours and other centres in patients with iTTP who have not tolerated rituximab, although some cross‐reactivity of side‐effects were described in one case 16–19 …”

“…13,15 Case reports of the successful use of both mAbs leading to disease remission have been described by ours and other centres in patients with iTTP who have not tolerated rituximab, although some cross-reactivity of side-effects were described in one case. [16][17][18][19] As a result of this, we aimed to evaluate the use of ofatumumab and obinutuzumab for iTTP in the UK to assess their clinical efficacy and safety profile in those who have not tolerated rituximab previously or shown poor responses.…”

Unresponsive Thrombotic Thrombocytopenic Purpura (TTP): Challenges and Solutions

“… 48 Patients who fail or become intolerant to rituximab may benefit from treatment with other anti-CD20 antibodies (eg obinutuzumab 49 or ofatumumab). 50 …”