Associations of ofatumumab exposure and treatment outcomes in patients with untreated CLL receiving chemoimmunotherapy

• Published in: Leukemia & lymphoma 2016-01, Vol.57 (6), p.1291-1299
• Main Authors: Jewell, Roxanne C., Kipps, Thomas J., Dürig, Jan, Griskevicius, Laimonas, Stilgenbauer, Stephan, Smolej, Lukáš, Mayer, Jiří, Hess, Georg, Hernandez-Ilizaliturri, Francisco J., Padmanabhan-Iyer, Swaminathan, Fang, Lei, Goldstein, Nancy, Gorczyca, Michele, Gupta, Ira, Lisby, Steen, Wierda, William G.
• Format: Article
• Language: English
• ISSN: 1042-8194; 1029-2403
• DOI: 10.3109/10428194.2015.1128540

Relationships between patient characteristics, ofatumumab pharmacokinetics, and treatment outcomes were investigated in this phase 2 trial of ofatumumab plus fludarabine and cyclophosphamide (FC) in untreated chronic lymphocytic leukemia. Patients were randomized 1:1 to receive 500 or 1000 mg ofatumumab (Cycle 1; 300 mg) plus FC every 4 weeks for six cycles. Median C max and C trough values were similar at Cycle 1 regardless of the ultimate clinical outcome. At later doses, these values were higher for patients with complete response (CR) than for other patients. Higher C max and C trough values at Cycles 3 and 6 were significantly associated with an increased likelihood of CR, whereas ofatumumab pharmacokinetics were not associated with an objective response (OR) on the basis of univariate analyses. Multivariate analyses indicated that baseline patient/disease factors were predominantly associated with CR (17p status) or OR (bulky lymphadenopathy, gender, and serum thymidine kinase), rather than ofatumumab pharmacokinetics. Trial registration: www.clinicaltrials.gov ( NCT00410163 ).