A distinctive form of immune thrombocytopenia in a phase 2 study of alemtuzumab for the treatment of relapsing-remitting multiple sclerosis.

Abstract

In a phase 2 clinical trial of annual alemtuzumab for treatment of relapsing-remitting multiple sclerosis, 6 of 216 patients (2.8%) developed immune thrombocytopenia (ITP). Over mean follow-up of 4.5 years, the incidence rate of ITP was 6.2 (95% confidence interval, 2.3-13.3) per 1000 person-years. Median times from initial and last alemtuzumab exposure to ITP diagnosis were 24.5 and 10.5 months, respectively. Five patients developed severe thrombocytopenia. Four were symptomatic, including fatal intracranial hemorrhage in the index case. Four patients received standard first-line ITP therapy, all of whom responded to treatment within 1 week. All 5 surviving patients achieved complete remission and remained in complete remission without need for ongoing ITP therapy for a median duration of 34 months at last follow-up. A monitoring plan for the early detection of ITP, implemented after presentation of the index case, identified all 5 subsequent cases before serious hemorrhagic morbidity or mortality occurred. In conclusion, we describe a distinctive form of ITP associated with alemtuzumab treatment characterized by delayed presentation after drug exposure, responsiveness to conventional ITP therapies, and prolonged remission. Clinicians should maintain a high level of vigilance and consider routine monitoring for ITP in patients treated with this agent. This trial was registered at www.clinicaltrials.gov as #NCT00050778.

• Authors: Adam Cuker, Alasdair J Coles, Herman Sullivan, Edward Fox, Mark Goldberg, Pedro Oyuela, Annie Purvis, Diana S Beardsley, David H Margolin
• Journal: Blood (Blood) Vol. 118 Issue 24 Pg. 6299-305 (Dec 08 2011) ISSN: 1528-0020 [Electronic] United States
• PMID: 21960587 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal, Humanized
• Antibodies, Neoplasm
• Antigens, CD
• Antigens, Neoplasm
• CD52 Antigen
• CD52 protein, human
• Glycoproteins
• Immunologic Factors
• Alemtuzumab

Topics

• Adult
• Alemtuzumab
• Antibodies, Monoclonal, Humanized (administration & dosage, adverse effects, therapeutic use)
• Antibodies, Neoplasm (administration & dosage, adverse effects, therapeutic use)
• Antigens, CD
• Antigens, Neoplasm
• CD52 Antigen
• Cohort Studies
• Drug Monitoring
• Early Termination of Clinical Trials
• Europe (epidemiology)
• Female
• Follow-Up Studies
• Glycoproteins (antagonists & inhibitors)
• Humans
• Immunologic Factors (administration & dosage, adverse effects, therapeutic use)
• Incidence
• Male
• Multiple Sclerosis, Relapsing-Remitting (blood, drug therapy, immunology, prevention & control)
• Platelet Count
• Purpura, Thrombocytopenic, Idiopathic (chemically induced, epidemiology, immunology, therapy)
• Remission Induction
• Secondary Prevention
• Severity of Illness Index
• United States (epidemiology)