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

Doyle, Andrew J.; Stubbs, Matthew; Lester, Will; Thomas, Will; Westwood, John‐Paul; Thomas, Mari; Percy, Charles H.; Prasannan, Nithya; Scully, Marie

doi:10.1111/bjh.18192

Cited by 12 publications

(12 citation statements)

References 27 publications

(67 reference statements)

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“…More recently, Ofatumumab and Obinutuzumab use has been reported by Doyle et al , 42 with treatment of 15 patients in 26 treatment episodes, ofatumumab ( n = 18) and obinutuzumab ( n = 8). In 21/26 cases, these agents were given as pre-emptive therapy to prevent a TTP relapse; in 12/15 cases, patients had previously developed serum sickness associated with rituximab.…”

Section: Use Of Elective Immunosuppressive Therapy To Prevent Ttp Rel...mentioning

confidence: 96%

“…These agents were generally well tolerated, with 4/26 (15%) episodes of adverse events, comprising two infections and two atopic episodes. 42 …”

Section: Use Of Elective Immunosuppressive Therapy To Prevent Ttp Rel...mentioning

confidence: 99%

“…These agents were generally well tolerated, with 4/26 (15%) episodes of adverse events, comprising two infections and two atopic episodes. 42 Other immunosuppressive agents MMF. MMF is an immunosuppressive agent that works by reducing B and T lymphocyte proliferation and antibody production.…”

Section: Ofatumumab and Obinutuzumabmentioning

confidence: 99%

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Management of acquired, immune thrombocytopenic purpura (iTTP): beyond the acute phase

Westwood¹,

Scully

2022

Therapeutic Advances in Hematology

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Modern therapy for acute TTP has resulted in a dramatic improvement in outcomes, with the combination of plasma exchange, immunosuppression, and caplacizumab being associated with >90% survival rates following an acute episode. TTP is no longer associated with just the acute episode, but requires long-term follow-up. There remains significant morbidity associated with acute TTP, and many patients suffer marked neuropsychological sequelae, including impairment in cognitive functioning, affective disorders, and reduction in health-related quality of life measures. The focus of management beyond the acute phase centres on relapse prevention, via careful monitoring of patients and the use of either ad hoc or regular immunosuppressive therapies. The main therapy used is rituximab, but despite more limited evidence, other immunosuppressive therapies may be required to aim for normalisation of ADAMTS 13 activity. Follow-up with a reduction in ADAMTS 13 activity levels (ADAMTS 13 relapse), rituximab is central to normalisation of activity levels and prevention of a clinical relapse. Fundamental to elective therapy is the role of ADAMTS 13 activity monitoring, and impact of reduced ADAMTS13 activity on end organ damage. This review discusses monitoring and treatment strategy for long-term management of TTP, including the variety of therapies available to maintain remission, prevent relapse and a summary of a long-term treatment pathway.

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Section: Use Of Elective Immunosuppressive Therapy To Prevent Ttp Rel...mentioning

confidence: 96%

“…These agents were generally well tolerated, with 4/26 (15%) episodes of adverse events, comprising two infections and two atopic episodes. 42 …”

Section: Use Of Elective Immunosuppressive Therapy To Prevent Ttp Rel...mentioning

confidence: 99%

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Management of acquired, immune thrombocytopenic purpura (iTTP): beyond the acute phase

Westwood¹,

Scully

2022

Therapeutic Advances in Hematology

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“…That is why the report by Doyle et al . showing the use of other anti‐CD20 monoclonal options in iTTP is an exciting study 1 . In this report it is shown that ofatumumab and obinutuzumab, both monoclonals with specificity to epitopes different from rituximab on CD20, can be effectively utilized in iTTP patients either not responding as expected or reacting adversely to rituximab.…”

mentioning

confidence: 89%

“…That is why the report by Doyle et al showing the use of other anti-CD20 monoclonal options in iTTP is an exciting study. 1 In this report it is shown that ofatumumab and obinutuzumab, both monoclonals with specificity to epitopes different from rituximab on CD20, can be effectively utilized in iTTP patients either not responding as expected or reacting adversely to rituximab. This report describes how these monoclonals were used as monotherapy pre-emptively if there was evidence of ADAMTS13 activity decrease or clinical suspicion of relapse, by either starting at lower test doses and then increasing them as tolerance to the medication was established or starting at a therapeutically appropriate larger dose while taking under consideration clinical need.…”

Section: Introductionmentioning

confidence: 96%

Anti‐CD20 therapeutic options in immune‐mediated thrombotic thrombocytopenic purpura

Maitta

2022

Br J Haematol

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Summary Immunosuppression with rituximab in immune‐mediated thrombotic thrombocytopenic purpura helps decrease production of autoantibody mediating ADAMTS13 clearance from circulation. Failure to respond to rituximab in a satisfactory way or made difficult by adverse events to the medication does not represent a reason to stop considering anti‐CD20 therapies to control antibody production. Therefore, both of atumumab and obinutuzumab with specificity to CD20, represent potentially valuable therapeutic tools in patients who are not candidates for rituximab. Commentary on: Doyle et al. The use of obinutuzumab and ofatumumab in the treatment of immune thrombotic thrombocytopenic purpura. Br J Haematol. 2022;198:391‐396.1

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Current state and potential applications of neonatal Fc receptor (FcRn) inhibitors in hematologic conditions

Jacobs,

Booth,

Raza

et al. 2024

American J Hematol

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The neonatal fragment crystallizable (Fc) receptor (FcRn) transports IgG across mucosal surfaces and the placenta and protects IgG from degradation. Numerous clinical trials are investigating therapeutic FcRn inhibition for various immune‐mediated neuromuscular and rheumatologic conditions; however, FcRn inhibition also represents a potential therapy for IgG‐mediated hematologic conditions (e.g., immune thrombocytopenia, autoimmune hemolytic anemia, immune thrombotic thrombocytopenic purpura, acquired hemophilia, red blood cell/platelet alloimmunization). Current evidence derived from both in vitro and in vivo studies suggests that FcRn inhibitors effectively reduce total IgG levels without impacting its production or altering the levels of other immunoglobulin isotypes. Moreover, the risk of serious adverse events, including serious infections, appears to be lower than that seen with other commonly used immunomodulatory/immunosuppressive therapies, albeit in the setting of limited clinical trial data. Ultimately, additional clinical trials that include varied patient populations are required prior to incorporating these agents into standard treatment algorithms for most hematologic conditions. However, based on the pathophysiology of IgG‐mediated hematologic disorders and the mechanism of action of FcRn inhibitors, these agents may represent a future novel therapeutic strategy for patients with hematologic conditions caused by IgG antibodies.

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

Cited by 12 publications

References 27 publications

Management of acquired, immune thrombocytopenic purpura (iTTP): beyond the acute phase

Management of acquired, immune thrombocytopenic purpura (iTTP): beyond the acute phase

Anti‐CD20 therapeutic options in immune‐mediated thrombotic thrombocytopenic purpura

Current state and potential applications of neonatal Fc receptor (FcRn) inhibitors in hematologic conditions

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