tes observed in practice. The adverse reaction information from clinical trials does, however, provide a basis for identifying the adverse events that appear to be related to drug use and for approximating rates.
Safety data, except where indicated, are based on 149 patients with B-CLL enrolled in studies of Campath as a single agent administered at a maintenance dose of 30 mg intravenously three times weekly for 4 to 12 weeks. Table 2 lists adverse events including severe or life threatening (NCI-CTC Grade 3 or 4) adverse events reported in > 5% of the patients. More detailed information and follow-up were available for Study 1 (93 patients), therefore the narrative description of certain events, noted below, is based on this study.
Infusion-Related Adverse Events:
Infusion-related adverse events resulted in discontinuation of Campath therapy in 6% of the patients enrolled in Study 1. The most commonly reported infusion-related adverse events on this study included rigors in 89% of patients, drug-related fever in 83%, nausea in 47%, vomiting in 33%, and hypotension in 15%. Other frequently reported infusion-related events include, rash in 30% of patients, fatigue in 22%, urticaria in 22%, dyspnea in 17%, pruritus in 14%, headache in 13%, and diarrhea in 13%. Similar types of adverse events were reported on the supporting studies (see Table 2). Acute infusion-related events were most common during the first week of therapy. Antihistamines, acetaminophen, antiemetics, meperidine, and corticosteroids as well as incremental dose escalation were used to prevent or ameliorate infusion-related events. (See WARNINGS and DOSAGE AND ADMINISTRATION.)
Infections:
On Study 1, all patients were required to receive anti-herpes and anti-PCP prophylaxis (see DOSAGE AND ADMINISTRATION) and were followed for infections for 6 months. Forty (43%) of 93 patients experienced 59 infections (one or more infections per patient) related to Campath during treatment or within 6 months of the last dose. Of these, 34 (37%) patients experienced 42 infections that were of Grade 3 or 4 severity; 11 (18%) were fatal. Fifty-five percent of the Grade 3 or 4 infections occurred during treatment or within 30 days of last dose. In addition one or more episodes of febrile neutropenia (ANC £ 500 cells/mL were reported in 10% of patients.
The following types of infections were reported in Study 1: Grade 3 or 4 sepsis in 12% of patients with one fatality, Grade 3 or 4 pneumonia in 15% with five fatalities, and opportunistic infections in 17% with four fatalities. Candida infections were reported in 5% of patients; CMV infections in 8% (4% of Grade 3 or 4 severity); Aspergillosis in 2% with fatal Aspergillosis in 1%; fatal Mucormycosis in 2%; fatal Cryptococcal pneumonia in 1%; Listeria monocytogenes meningitis in 1%; disseminated Herpes zoster in 1%; Grade 3 Herpes simplex in 2%; and Torulopsis pneumonia in 1%. PCP pneumonia occurred in one (1%) patient who discontinued PCP prophylaxis.
On Studies 2 and 3 in which anti-herpes and anti-PCP prophylaxis was optional, 37 (66%) patients had 47 infections while or after receiving Campath therapy. In addition to the opportunistic infections reported above, the following types of related events were observed on these studies: interstitial pneumonitis of unknown etiology and progressive multifocal leukoencephalopathy.
Hematologic Adverse Events:
Pancytopenia/Marrow Hypoplasia: Campath therapy was permanently discontinued in six (6%) patient |
