Chemoimmunotherapy with ofatumumab, fludarabine, and cyclophosphamide (O-FC) in previously untreated patients with chronic lymphocytic leukemia

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BlankChemoimmunotherapy with ofatumumab, fludarabine, and cyclophosphamide

(O-FC) in previously untreated patients with chronic lymphocytic leukemia.

WG Wierda, TJ Kipps, J Durig, L Griskevicius, S Stilgenbauer, J Mayer, L Smolej,

G Hess, R Griniute, FJ -Ilizaliturri, S Padmanabhan, M Gorczyca, CN

Chang, G Chan, I Gupta, TG Nielsen, and CA

Blood, April 15, 2011; .

We conducted an international phase II trial to evaluate two dose levels of

ofatumumab, a human CD20 monoclonal antibody, combined with fludarabine and

cyclophosphamide (O-FC) as frontline therapy for chronic lymphocytic leukemia

(CLL). Patients with active CLL were randomized to ofatumumab 500 mg (n=31) or

1000 mg (n=30) day 1, with fludarabine 25 mg/m(2) and cyclophosphamide 250

mg/m(2) days 2-4, course 1; days 1-3, courses 2-6; every 4 weeks for 6 courses.

First ofatumumab dose was 300 mg for both cohorts. The median age was 56 years;

13% of patients had 17p deletion; 64% had ?2-microglobulin > 3.5 mg/L. Complete

response (CR) rate (1996 NCI-WG criteria) assessed by an Independent Review

Committee was 32% for the 500-mg and 50% for the 1000-mg cohort; overall

response rate (ORR) was 77% and 73%, respectively. Based on univariable

regression analyses, ?2-microglobulin and number of O-FC courses were

significantly correlated (P<.05) with CR, ORR and progression-free survival.

Most common CTC grade 3-4 investigator-reported adverse events were neutropenia

(48%), thrombocytopenia (15%), anemia (13%) and infection (8%). O-FC is active

and safe in treatment-naive patients with CLL, including in patients with

high-risk features. This trial was registered at http://www.clinicaltrials.gov

(NCT00410163).

PMID: 21498674