TY - JOUR
T1 - Associations of ofatumumab exposure and treatment outcomes in patients with untreated CLL receiving chemoimmunotherapy
AU - for the Hx-CD20-407 Study Investigators
AU - Jewell, Roxanne C.
AU - Kipps, Thomas J.
AU - Dürig, Jan
AU - Griskevicius, Laimonas
AU - Stilgenbauer, Stephan
AU - Smolej, Lukáš
AU - Mayer, Jiří
AU - Hess, Georg
AU - Hernandez-Ilizaliturri, Francisco J.
AU - Padmanabhan-Iyer, Swaminathan
AU - Fang, Lei
AU - Goldstein, Nancy
AU - Gorczyca, Michele
AU - Gupta, Ira
AU - Lisby, Steen
AU - Wierda, William G.
N1 - Publisher Copyright:
© 2016 Informa UK Limited, trading as Taylor & Francis Group.
PY - 2017/2/1
Y1 - 2017/2/1
N2 - 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 Cmax and Ctrough 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 Cmax and Ctrough 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).
AB - 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 Cmax and Ctrough 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 Cmax and Ctrough 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).
KW - Chemoimmunotherapy
KW - chronic lymphocytic leukemia
KW - ofatumumab
KW - pharmacokinetics
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U2 - 10.1080/10428194.2016.1195497
DO - 10.1080/10428194.2016.1195497
M3 - Article
C2 - 27389174
AN - SCOPUS:84978984468
SN - 1042-8194
VL - 58
SP - 348
EP - 356
JO - Leukemia and Lymphoma
JF - Leukemia and Lymphoma
IS - 2
ER -