1 Per Patient Incidence of Selected Adverse reactions occurring at a higher relative frequency in the Campath arm Adverse Reactions in Treatment Naive B-CLL Patients
Campath (n=147) Chlorambucil (n=147)
All Grades NCI CTC version 2.0 for adverse reactions; NCI CTCAE version 3.0 for laboratory values
% Grades 3-4
% All Grades
% Grades
3-4
%
Blood and Lymphatic System Disorders Lymphopenia 97 97 9 1
Neutropenia 77 42 51 26
Anemia 76 13 54 18
Thrombocytopenia 71 13 70 14
General Disorders and Administration Site Conditions Pyrexia 69 10 11 1
Chills 53 3 1 0
Infections and Infestations CMV viremia CMV viremia (without evidence of symptoms) includes both cases of single PCR positive test results and of confirmed CMV viremia (≥ 2 occasions in consecutive samples 1 week apart). For the latter, ganciclovir (or equivalent) was initiated per protocol. 55 4 8 0
CMV infection 16 5 0 0
Other infections 74 21 65 10
Skin and Subcutaneous Tissue Disorders Urticaria 16 2 1 0
Rash 13 1 4 0
Erythema 4 0 1 0
Vascular Disorders Hypotension 16 1 0 0
Hypertension 14 5 2 1
Nervous System Disorders Headache 14 1 8 0
Tremor 3 0 1 0
Respiratory, Thoracic and Mediastinal Disorders Dyspnea 14 4 7 3
Gastrointestinal Disorders Diarrhea 10 1 4 0
Psychiatric Disorders Insomnia 10 0 3 0
Anxiety 8 0 1 0
Cardiac Disorders Tachycardia 10 0 1 0
As with all therapeutic proteins, there is potential for immunogenicity. Using an ELISA assay, anti-human antibodies (HAHA) were detected in 11 of 133 (8.3%) previously untreated patients. In addition, two patients were weakly positive for neutralizing activity. Limited data suggest that the anti-Campath antibodies did not adversely affect tumor response. Four of 211 (1.9%) previously-treated patients were found to have antibodies to Campath following treatment.
The incidence of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to Campath with the incidence of antibodies to other products may be misleading.
The following adverse reactions were identified during post-approval use of Campath. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to Campath exposure. Decisions to include these reactions in labeling are typically based on one or more of the following factors: (1) seriousness of the reaction, (2) reported frequency of the reaction, or (3) strength of causal connection to Campath.
Fatal infusion reactions: [see WARNINGS AND PRECAUTIONS (5.2) ] .
Cardiovascular: congestive heart failure, cardiomyopathy, decreased ejection fraction (some patients had been previously treated with cardiotoxic agents).
Immune disorders: Goodpasture’s syndrome, Graves’ disease, aplastic anemia, Guillain Barré syndrome, chronic inflammatory demyelinating polyradiculoneuropathy, serum sickness, fatal transfusion associated |
