Ofatumumab + Chlorambucil versus Chlorambucil Alone in Patients with Untreated Chronic Lymphocytic Leukemia: Results of the Phase 3 Study Complement 1 (OMB110911)

Although chlorambucil (Clb) remains a standard option for elderly patients with chronic lymphocytic leukemia (CLL), more effective and tolerable treatment choices are needed. Compared with rituximab, ofatumumab (OF) demonstrated superior preclinical activity in CLL cells1 and has demonstrated clinical activity as monotherapy in patients with refractory CLL.2 This preclinical and clinical data suggest that the combination of OF plus Clb could be a potential treatment option for patients who are elderly and/or have comorbidities. 

In this phase 3 study conducted by Hillmen and colleagues, a total of 447 patients with CLL who required treatment but were not eligible for fludarabine-based therapy were randomized to receive either OF-Clb or Clb alone; Clb was given orally on days 1 to 7 of each 28-day cycle, and OF was administered as intravenous infusions on day 1 and day 8 of cycle 1 and on day 1 of subsequent cycles.3 Baseline demographics and disease characteristics were well balanced between the study arms. The treatment duration was a minimum of 3 cycles until the best response was reached, with a maximum of 12 cycles. The primary end point was progression-free survival (PFS), and secondary end points included overall response rate (ORR), overall survival (OS), and safety.3

An independent review committee found significantly prolonged PFS in the OF-Clb arm compared with the Clb arm (22.4 vs 13.1 months; P<.001). The ORR was higher in the OF-Clb arm than it was in the Clb arm (82% vs 69%; P=.001), with a superior complete response (CR) rate (12% vs 1%). In addition, among the patients who achieved CR with OF-Clb, 37% were minimal residual disease negative. With a median follow-up of 29 months, the median OS was not reached for either study arm. The median duration of treatment for both arms was 6 cycles; 82% of patients received 6 or more cycles of OF-Clb.3

The most common grade 3 or higher adverse events among patients receiving OF-Clb were neutropenia, infusion-related reactions, and infections. Deaths during treatment occurred in 2% of patients in both arms.3

Hillmen and colleagues concluded that OF-Clb demonstrated efficacy and has a manageable safety profile in patients with CLL who have not received previous treatment and who are considered ineligible for fludarabine-based therapy.3

References

  1. Barth M, Hernandez-Ilizaliturri FJ, Mavis C, et al. Ofatumumab, a fully human monoclonal antibody targeting CD20, demonstrates activity against and potentiates the anti-tumor activity of chemotherapy agents in rituximab-sensitive cell lines (RSCL), rituximab-resistant cell lines (RRCL), lymphoma xenografts, and primary tumor cells derived from patients with B-cell non-Hodgkin lymphoma (NHL). Blood. 2010;116(21). Abstract 3917.
  2. Wierda WG, Kipps TJ, Mayer J, et al. Ofatumumab as single-agent CD20 immunotherapy in fludarabine-refractory chronic lymphocytic leukemia. J Clin Oncol. 2010;28(10):1749–1755.
  3. Hillmen P, Robak T, Janssens A, et al. Ofatumumab + chlorambucil versus chlorambucil alone in patients with untreated chronic lymphocytic leukemia (CLL): results of the phase III study complement 1 (OMB110911). Blood. 2013;122(21). Abstract 528.
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