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

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/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. 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.

Figures

Figure 1

CONSORT (Consolidated Standards Of Reporting Trials) diagram. Phase 2 study of O-FC in previously untreated patients with CLL.

Figure 2

PFS and OS in patients treated with O-FC. (A) PFS in patients (N = 61) treated with O-FC. PFS was defined as the time from randomization until disease progression or death. Median follow-up time was 8 months. (B) OS in patients (N = 61) treated with O-FC. OS was defined as the time from randomization until death. Median follow-up time was 8 months.

Figure 3

Ofatumumab infusion–related reactions over the course of treatment. All patients received ofatumumab 300 mg for course 1. All infusion reactions on the day of ofatumumab infusion were CTC grade 1 or 2 events.

Figure 4

Incidence of laboratory-assessed CTC grade 3 or 4 neutropenia by treatment course. Laboratory values were assigned to treatment course based on date of laboratory measurement in relation to ofatumumab infusion.

Figure 5

Incidence of laboratory-assessed CTC grade 3 or 4 anemia by treatment course. Laboratory values were assigned to treatment course based on date of laboratory measurement in relation to ofatumumab infusion.

Figure 6

Incidence of laboratory-assessed CTC grade 3 or 4 thrombocytopenia by treatment course. Laboratory values were assigned to treatment course based on date of laboratory measurement in relation to ofatumumab infusion.