Therapeutic role of alemtuzumab (Campath-1H) in patients who have failed fludarabine: results of a large international study

• Published in: Blood Vol. 99; no. 10; pp. 3554 - 3561
• Main Authors: Keating, Michael J., Flinn, Ian, Jain, Vinay, Binet, Jacques-Louis, Hillmen, Peter, Byrd, John, Albitar, Maher, Brettman, Lee, Santabarbara, Pedro, Wacker, Bret, Rai, Kanti R.
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 15.05.2002; The Americain Society of Hematology
• Subjects: Adult; Aged; Alemtuzumab; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal - adverse effects; Antibodies, Monoclonal - therapeutic use; Antibodies, Monoclonal, Humanized; Antibodies, Neoplasm - administration & dosage; Antibodies, Neoplasm - adverse effects; Antibodies, Neoplasm - therapeutic use; Antineoplastic agents; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - adverse effects; Antineoplastic Agents - therapeutic use; Biological and medical sciences; Chemotherapy; Demography; Hematologic and hematopoietic diseases; Humans; Immunocompromised Host; Infections - etiology; Infusions, Intravenous; Leukemia, Lymphocytic, Chronic, B-Cell - diagnosis; Leukemia, Lymphocytic, Chronic, B-Cell - drug therapy; Leukemia, Lymphocytic, Chronic, B-Cell - therapy; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymphocyte Count; Medical sciences; Middle Aged; Neoplasm Recurrence, Local - drug therapy; Neoplasm Recurrence, Local - therapy; Neutropenia - etiology; Pharmacology. Drug treatments; Salvage Therapy; Survival Rate; Thrombocytopenia - etiology; Treatment Failure; Treatment Outcome; Vidarabine - analogs & derivatives; Vidarabine - therapeutic use; Antineoplastic agent; Human; Purine nucleotide; Relapse; Treatment resistance; Malignant hemopathy; B-Lymphocyte; Alemtuzumab; Monoclonal antibody; Chemotherapy; Chronic; Chronic lymphocytic leukemia; Fludarabine; Treatment; Lymphoproliferative syndrome; Immunotherapy; CAMPATH
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V99.10.3554

This study investigated the efficacy, safety, and clinical benefit of alemtuzumab (Campath-1H) for patients with relapsed or refractory B-cell chronic lymphocytic leukemia exposed to alkylating agents and having failed fludarabine therapy. Ninety-three patients received alemtuzumab in 21 centers worldwide, with the aim to obtain an overall response rate of at least 20%. Dosage was increased gradually (target 30 mg, 3 times weekly, for a maximum of 12 weeks). Infection prophylaxis was mandatory, beginning on day 8, and continuing for a minimum of 2 months after treatment. Responses were assessed at weeks 4, 8, and 12, and patients were followed for 34 months. Overall objective response in the intent-to-treat population (n = 93) was 33% (CR 2%, PR 31%). Median time to response was 1.5 months (range, 0.4-3.7 months). Median time to progression was 4.7 months overall, 9.5 months for responders. At data cut-off, 27 patients (29%) were alive; overall median survival was 16 months (95% CI: 11.8-21.9) and 32 months for responders. Nineteen responders survived more than 21 months. Clinical benefit was observed both in responders and in patients with stable disease. The most common adverse events were related to infusion, generally grade 1 or 2 in severity, occurring mainly in the first week. Grade 3 or 4 infections were reported in 25 patients (26.9%). However, only 3 (9.7%) of 31 patients who responded to alemtuzumab treatment developed grade 3 or 4 infections on the study. Alemtuzumab induced significant responses in these patients with clinical benefit in the majority and with acceptable toxicity in a high-risk group.