ade 3 or 4 anemia was 38%. Seventeen percent of previously untreated patients and 66% of previously treated patients received either erythropoiesis stimulating agents, transfusions or both.
Thrombocytopenia: In previously untreated patients, the incidence of Grade 3 or 4 thrombocytopenia was 14% with a median time to onset of 9 days and a median duration of 14 days. In previously treated patients, the incidence of Grade 3 or 4 thrombocytopenia was 52% with a median duration of 21 days. Autoimmune thrombocytopenia was reported in 2% of previously treated patients with one fatality.
Infusion reactions: Infusion reactions, which included pyrexia, chills, hypotension, urticaria, and dyspnea, were common. Grade 3 and 4 pyrexia and/or chills occurred in approximately 10% of previously untreated patients and in approximately 35% of previously treated patients. The occurrence of infusion reactions was greatest during the initial week of treatment and decreased with subsequent doses of Campath. All patients were pretreated with antipyretics and antihistamines; additionally, 43% of previously untreated patients received glucocorticoid pre-treatment.
Infections: In the study of previously untreated patients, patients were tested weekly for CMV using a PCR assay from initiation through completion of therapy, and every 2 weeks for the first 2 months following therapy. CMV infection occurred in 16% (23/147) of previously untreated patients; approximately one-third of these infections were serious or life threatening. In studies of previously treated patients in which routine CMV surveillance was not required, CMV infection was documented in 6% (9/149) of patients; nearly all of these infections were serious or life threatening.
Other infections were reported in approximately 50% of patients across all studies. Grade 3 - 5 sepsis ranged from 3% to 10% across studies and was higher in previously treated patients. Grade 3 - 4 febrile neutropenia ranged from 5 to 10% across studies and was higher in previously treated patients. Infection-related fatalities occurred in 2% of previously untreated patients and 16% of previously treated patients. There were 198 episodes of other infection in 109 previously untreated patients; 16% were bacterial, 7% were fungal, 4% were other viral, and in 73%, the organism was not identified.
Cardiac: Cardiac dysrhythmias occurred in approximately 14% of previously untreated patients. The majority were tachycardias and were temporally associated with infusion; dysrhythmias were Grade 3 or 4 in 1% of patients.
Previously Untreated Patients
Table 1 contains selected adverse reactions observed in 294 patients randomized (1:1) to receive Campath or chlorambucil as first line therapy for B-CLL. Campath was administered at a dose of 30 mg intravenously three times weekly for up to 12 weeks. The median duration of therapy was 11.7 weeks with a median weekly dose of 82 mg (25-75% interquartile range: 69 mg – 90 mg).
Previously Treated Patients
Additional safety information was obtained from 3 single arm studies of 149 previously treated patients with CLL administered 30 mg Campath intravenously three times weekly for 4 to 12 weeks (median cumulative dose 673 mg [range 2 – 1106 mg]; median duration of therapy 8.0 weeks). Adverse reactions in these studies not listed in Table 1 that occurred at an incidence rate of > 5% were fatigue, nausea, emesis, musculoskeletal pain, anorexia, dysesthesia, mucositis, and bronchospasm.
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