NEW ORLEANS—Adding ofatumumab to chlorambucil prolonged progression-free survival (PFS) in patients with untreated chronic lymphocytic leukemia (CLL) considered inappropriate for treatment with fludarabine-based therapy due to age or comorbidities, a study concluded at the 55th American Society of Hematology Annual Meeting and Exposition.

“Most randomized studies in previously untreated CLL have been conducted in younger or fit patients and results cannot necessarily be extrapolated to older, less fit patients,” said Peter Hillmen, MB ChB, PhD, of St. James’s University Hospital, Leeds, United Kingdom.

The phase 3 Complement 1 (OMB110911) study randomly assigned 447 patients from 16 countries to receive intravenous ofatumumab (300 mg day 1 and 1,000 mg day 8 in cycle 1 and 1,000 mg day 1 in subsequent cycles) plus oral chlorambucil (10 mg/m2 days 1 to 7 of each 28-day cycle) or chlorambucil alone. Patients were treated for a minimum of three cycles until best response, to a maximum of 12 cycles.

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Median age was 69 years; 82% of patients were 65 years of age or older and/or had two or more comorbidities. All modified Rai stages were represented: low, 8%; intermediate, 51%; and high, 40%. A total of 56% of patients had unmutated IgVH, 6% showed 17p deletions, and 75% had β-2-microglobulin levels 3,500 μg/L or higher.

As assessed by an independent review committee, PFS, the primary end point, was 22.4 months (95% CI: 19.0-25.2 months) in the ofatumumab plus chlorambucil arm versus 13.1 months (95% CI: 10.6-13.8 months) in the chlorambucil alone arm (hazard ratio, 0.57; P < 0.001). Overall response rate was also higher; 82% versus 69%, respectively (P < 0.001); complete response rate was 14% versus 1%, and partial response rate, 67% versus 68%. Of the patients who received the combination regimen who had a complete response, 37% were minimal residual disease–negative.

At a median follow-up of 28.9 months, median overall survival (OS) was not reached for patients in either arm (P = 0.666). For both arms, median duration of treatment was six cycles with 82% of patients receiving six or more cycles of ofatumumab plus chlorambucil.

Two-year and 3-year OS was 86.7% and 83.2% in the chlorambucil arm, respectively, and 88.7% and 85.1% in the ofatumumab plus chlorambucil arm.

A total of 50% of patients in the ofatumumab plus chlorambucil arm and 43% of those in the chlorambucil-alone arm experienced grade 3 or higher adverse events (AEs). The most common was neutropenia (26% vs. 14%). Grade 3 or higher infusion-related AEs were reported in 10% of patients in the ofatumumab plus chlorambucil arm. No fatal infusion reactions were reported. Grade 3 or higher infections were reported in 9% of patients in the ofatumumab plus chlorambucil arm and 12% in the chlorambucil-alone arm. Four patients in the ofatumumab plus chlorambucil and three in the chlorambucil-alone arms died.

Improved and durable minimal residual disease (MRD) negativity was also improved in all subjects, 12% with ofatumumab plus chlorambucil versus 4% for chlorambucil alone, regardless of response of MRD sample available; for patients with complete responses, MRD negativity was 38% versus 0%, respectively.

“Ofatumumab added to chlorambucil in previously untreated patients with CLL who are considered inappropriate for fludarabine-based therapy demonstrated effective treatments with clinically meaningful improvements,” said Dr. Hillmen, with a side effect profile that is expected and manageable.

The combination “improved efficacy irrespective of age or fitness,” he concluded, making it “suitable for an unfit patient population.”


  1. Hillmen P et al. Abstract #528. Presented at: American Society of Hematology Meeting 2013. Dec. 7-10, 2013; New Orleans.