Safety and Efficacy of Rituximab and Cyclophosphamide in a Case of Resistant Acquired Hemophilia A in Course of Chronic Lymphocytic Leukemia

Abstract Abstract 2224 Introduction OBI-1 is an investigational B-domain deleted recombinant porcine factor VIII (FVIII) with low cross-reactivity to anti-human FVIII antibodies. Acquired hemophilia A (AHA) is caused by autoantibodies (inhibitors) against human FVIII. Patients are predominantly elderly and have co-morbidities. Current pharmacologic treatment of bleeds is guided by clinical assessment alone as there is no laboratory surrogate for efficacy. Importantly, OBI-1 efficacy can be monitored by FVIII levels in addition to clinical assessment. Methods Accur8 Auto-antibody trial (NCT01178294) is a prospective, open label, Phase 2/3 study. The primary objective is to evaluate efficacy of OBI-1 treatment for serious (life- or limb-threatening) bleeds in patients ≥18 years with AHA. FVIII levels are obtained before and within 10–20 min following initial OBI-1 dose (200U/kg) and at 2–3 h. Additional OBI-1 doses (≤400U/kg every 2–3 h) are administered to achieve target FVIII levels. The primary efficacy outcome is the control of bleeding 24 h after starting OBI-1. Results As of July, 2012, fifteen patients with severe bleeds were entered into the trial along with one individual treated under compassionate use and all had successful control of hemorrhage at 24 h and subsequent resolution of the bleed. Therapeutic FVIII activity levels were achieved and maintained with intermittent OBI-1 administration based on FVIII levels. Six serious adverse events were reported including four deaths after treatment was discontinued, all being unrelated to OBI-1 as determined by the investigators. Antibodies to OBI-1 developed in two subjects indicated with an * in the table below. However, both responded toOBI-1. Conclusions These interim results provide support for the safety and efficacy of OBI-1 in the treatment of serious bleeding episodes in AHA. Additional confirming data could establish OBI-1 as a useful treatment option for AHA. Disclosures: St. Louis: Inspiration Biopharmaceuticals Inc: Research Funding. Kruse-Jarres:Inspiration Biopharmaceiticals Inc: Research Funding. Greist:Inspiration Biopharmaceuticals Inc: Research Funding. Shapiro:Inspiration Biopharmaceuticals Inc: Research Funding. Smith:Inspiration Biopharmaceuticals Inc: Research Funding. Drebes:Inspiration Biopharmaceuticals Inc: Research Funding. Gomperts:Inspiration Biopharmaceuticals Inc: Consultancy.

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To Evaluate the Safety and Tolerability, Find an Appropriate Dose to Optimize Safety and Efficacy, and Evaluate Clinical Activity of PBCAR20A in Subjects With Relapsed/Refractory (r/r) Non-Hodgkin Lymphoma (NHL) or r/r Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL)

Case Medical Research ◽

10.31525/ct1-nct04030195 ◽

2019 ◽

Author(s):

Keyword(s):

Chronic Lymphocytic Leukemia ◽

Hodgkin Lymphoma ◽

Lymphocytic Leukemia ◽

Clinical Activity ◽

Small Lymphocytic Lymphoma ◽

Safety And Efficacy ◽

Non Hodgkin Lymphoma

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Matching-adjusted indirect comparisons of safety and efficacy of acalabrutinib versus other targeted therapies in patients with treatment-naïve chronic lymphocytic leukemia

Leukemia & Lymphoma ◽

10.1080/10428194.2021.1913144 ◽

2021 ◽

pp. 1-16

Author(s):

Matthew S. Davids ◽

Claire Telford ◽

Sarang Abhyankar ◽

Catherine Waweru ◽

Ingo Ringshausen

Keyword(s):

Chronic Lymphocytic Leukemia ◽

Targeted Therapies ◽

Lymphocytic Leukemia ◽

Safety And Efficacy ◽

Treatment Naïve ◽

Indirect Comparisons

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Successful Management of Acquired Hemophilia A Associated with Bullous Pemphigoid: A Case Report and Review of the Literature

Case Reports in Hematology ◽

10.1155/2017/2057019 ◽

2017 ◽

Vol 2017 ◽

pp. 1-7 ◽

Cited By ~ 4

Author(s):

Quentin Binet ◽

Catherine Lambert ◽

Laurine Sacré ◽

Stéphane Eeckhoudt ◽

Cedric Hermans

Keyword(s):

Bullous Pemphigoid ◽

Neutralizing Antibodies ◽

Hemophilia A ◽

Rare Condition ◽

Term Treatment ◽

Acquired Hemophilia A ◽

Acquired Hemophilia ◽

Short Term Treatment ◽

Life Threatening ◽

Dose Levels

Background. Acquired hemophilia A (AHA) is a rare condition, due to the spontaneous formation of neutralizing antibodies against endogenous factor VIII. About half the cases are associated with pregnancy, postpartum, autoimmune diseases, malignancies, or adverse drug reactions. Symptoms include severe and unexpected bleeding that may prove life-threatening.Case Study. We report a case of AHA associated with bullous pemphigoid (BP), a chronic, autoimmune, subepidermal, blistering skin disease. To our knowledge, this is the 25th documented case of such an association. Following treatment for less than 3 months consisting of methylprednisolone at decreasing dose levels along with four courses of rituximab (monoclonal antibody directed against the CD20 protein), AHA was completely cured and BP well-controlled.Conclusions. This report illustrates a rare association of AHA and BP, supporting the possibility of eradicating the inhibitor with a well-conducted short-term treatment.

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