Ofatumumab is active in patients with fludarabine-refractory CLL irrespective of prior rituximab: results from the phase 2 international study

• Published in: Blood Vol. 118; no. 19; pp. 5126 - 5129
• Main Authors: Wierda, William G., Padmanabhan, Swaminathan, Chan, Geoffrey W., Gupta, Ira V., Lisby, Steen, Österborg, Anders
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 10.11.2011; Americain Society of Hematology; American Society of Hematology
• Subjects: Adult; Aged; Aged, 80 and over; Alemtuzumab; Antibodies, Monoclonal - therapeutic use; Antibodies, Monoclonal, Humanized - therapeutic use; Antibodies, Monoclonal, Murine-Derived - therapeutic use; Antibodies, Neoplasm - therapeutic use; Antineoplastic Agents - therapeutic use; Biological and medical sciences; Brief Report; Clinical Trials and Observations; Disease-Free Survival; Female; Hematologic and hematopoietic diseases; Humans; Kaplan-Meier Estimate; Leukemia, Lymphocytic, Chronic, B-Cell - drug therapy; Leukemia, Lymphocytic, Chronic, B-Cell - therapy; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymphoid Neoplasia; Male; Medical sciences; Medicin och hälsovetenskap; Middle Aged; Retrospective Studies; Rituximab; Vidarabine - analogs & derivatives; Vidarabine - therapeutic use; Antineoplastic agent; Human; Purine nucleotide; Treatment resistance; Hematology; Rituximab; Malignant hemopathy; Nucleotide analog; Monoclonal antibody; Ofatumumab; Chronic lymphocytic leukemia; Fludarabine; Treatment; Antimetabolic; Lymphoproliferative syndrome; Immunotherapy; Phase II trial; Fluorine Organic compounds; Cancer; International
• ISSN: 0006-4971; 1528-0020; 1528-0020
• DOI: 10.1182/blood-2011-04-348656

Ofatumumab, the human CD20 monoclonal antibody that binds a distinct epitope from rituximab, has demonstrated clinical benefit as monotherapy for patients with chronic lymphocytic leukemia refractory to fludarabine and alemtuzumab (FA-ref) and patients refractory to fludarabine with bulky (> 5 cm) lymph nodes (BF-ref). To potentially gain insight into outcomes in patients previously treated with or refractory to rituximab, we performed an ad hoc retrospective analysis in the final 96 FA-ref and 111 BF-ref patients. There were 117 patients previously treated with rituximab (98 rituximab-refractory); 89 patients were rituximab-naive. For rituximab-treated, rituximab-refractory, and rituximab-naive patients, overall response rate was 43%, 44%, and 53%; median progression-free survival was 5.3, 5.5, and 5.6 months; and median overall survival was 15.5, 15.5, and 20.2 months. There were no significant differences in ofatumumab-related infusion reactions, or hematologic or infectious adverse events between subgroups. In summary, ofatumumab monotherapy was effective and well tolerated in patients with fludarabine-refractory chronic lymphocytic leukemia, including in patients with previous rituximab exposure. This trial was registered at www.clinicaltrials.gov as #NCT00349349.