Chemoimmunotherapy with O-FC in previously untreated patients with chronic lymphocytic leukemia

Chemoimmunotherapy with O-FC in previously untreated patients with chronic lymphocytic leukemia

William G. Wierda1, Thomas J. Kipps2, Jan Dürig3, Laimonas Griskevicius4, Stephan Stilgenbauer5, Jiří Mayer6, Lukáš Smolej7, Georg Hess8, Rasa Griniute9, Francisco J. Hernandez-Ilizaliturri10, Swaminathan Padmanabhan11, Michele Gorczyca12, Chai-Ni Chang13, Geoffrey Chan12, Ira Gupta12, Tina G. Nielsen14, and Charlotte A. Russell14 on behalf of the 407 Study Investigators


+ Author Affiliations

1The University of Texas M. D. Anderson Cancer Center, Houston, TX;
2University of California-San Diego Moores Cancer Center, La Jolla, CA;
3Klinik für Hämatologie Huflandstr, Universitätsklinikum Essen, Essen, Germany;
4Vilnius University Hospital Santariskiu Clinics, Vilnius, Lithuania;
5Department of Internal Medicine III, Universitätsklinikum Ulm, Ulm, Germany;
6Department of Internal Medicine/Hemato-Oncology, Faculty Hospital Brno, Brno, Czech Republic;
72nd Department of Internal Medicine, Department of Clinical Hematology, University Hospital and Faculty of Medicine, Hradec Kralove, Czech Republic;
8Johannes Gutenberg University, Mainz, Germany;
9Kaunas Medical University, Kaunas, Lithuania;
10Roswell Park Cancer Institute, Buffalo, NY;
11Cancer Therapy & Research Center, San Antonio, TX (formerly Roswell Park Cancer Institute, Buffalo, NY);
12GlaxoSmithKline, Collegeville, PA;
13GlaxoSmithKline, Research Triangle Park, NC; and
14Genmab, Copenhagen, Denmark
1.Data from this study were presented in part at the American Society of Hematology Annual Meeting, December 5-8, 2009, New Orleans, LA; the American Society of Clinical Oncology Annual Meeting, June 4-8, 2010, Chicago, IL; and the Congress of the European Hematology Association, June 10-13, 2010, Barcelona, Spain.

Abstract
We conducted an international phase 2 trial to evaluate 2 dose levels of ofatumumab, a human CD20 mAb, 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/m2 and cyclophosphamide 250 mg/m2 days 2-4, course 1; days 1-3, courses 2-6; every 4 weeks for 6 courses. The first ofatumumab dose was 300 mg for both cohorts. The median age was 56 years; 13% of patients had a 17p deletion; 64% had β2-microglobulin > 3.5 mg/L. Based on the 1996 National Cancer Institute Working Group (NCI-WG) guidelines, the complete response (CR) rate as assessed by an independent review committee was 32% for the 500-mg and 50% for the 1000-mg cohort; the overall response (OR) rate was 77% and 73%, respectively. Based on univariable regression analyses, β2-microglobulin and the number of O-FC courses were significantly correlated (P < .05) with CR and OR rates and progression-free survival (PFS). The most frequent Common Terminology Criteria (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 high-risk patients. This trial was registered at www.clinicaltrials.gov as NCT00410163. full-text: Chemoimmunotherapy with O-FC in previously untreated patients with chronic lymphocytic leukemia