Head-To-Head Comparison of Obinutuzumab Plus Chlorambucil versus Rituximab Plus Chlorambucil in Patients with Chronic Lymphocytic Leukemia and Coexisting Medical Conditions: Final Stage 2 Results of the CLL11 Trial

Goede and colleagues presented findings from the CLL11 trial, a large, randomized, phase 3 study of first-line chemoimmunotherapy regimens in patients with chronic lymphocytic lymphoma (CLL) who have comorbidities.¹ Research authors presented on the following study results:

1. The final stage 2 analysis with efficacy and safety results of the direct comparison between the anti-CD20 antibody, obinutuzumab (O), plus chlorambucil (Clb) and rituximab (R) plus Clb; at the preplanned interim analysis, the primary end point was met early, such that results were released by the independent data monitoring board.
   
2. Updated results from the stage 1 analysis, which compared OClb versus Clb and RClb versus Clb, with longer observation time; in terms of efficacy, the final stage 1 analysis recently showed that OClb or RClb is superior to Clb monotherapy.

The CLL11 trial included 781 treatment-naïve patients with CLL who had a Cumulative Illness Rating Scale total score >6 and/or an estimated creatinine clearance <70 mL/min; the patients’ median age was 73 years. Researchers assigned 333 patients to OClb, 330 patients to RClb, and 118 patients to Clb monotherapy.

The primary outcome measure in the CL11 trial was progression-free survival (PFS); secondary outcome measures included response rates, minimal residual disease (MRD), and overall survival (OS). The median observation time was 19 months. Goede and colleagues reported higher median PFS in the OClb arm versus the RClb arm (26.7 vs 15.2 months; hazard ratio, 0.39; P<.0001). Furthermore, a higher overall response rate (78% vs 65%; P<.0001) and complete response rate (21% vs 7%) were reported in the OClb arm compared with response rates in the RClb arm. In addition, the number of patients with MRD-negative blood samples at end-of-treatment was more than 10-fold higher with OClb compared with RClb (29% vs 2.5%). To date, 9%, 15%, and 20% of the patients in the OClb, RClb, and Clb arms, respectively, died. The median OS rates have not been reached.

Grade 3 to 5 adverse events, including infusion-related reactions and neutropenia, were more common among patients receiving the OClb combination. Infection risk was similar between the 2 arms (12% for OClb vs 14% for RClb).

“Our results suggest [obinutuzumab] may be a stronger CD20 antibody than rituximab,” Goede said in a press release.² “This could lead to a potential decrease in the total amount of chemotherapy required for an effective combination regimen, translating to less toxicity for the patient. While we continue to evaluate these results through a longer follow-up period, these findings suggest that [obinutuzumab] has the potential to eventually replace rituximab for the care of CLL patients.”²

References

1. Goede V, Fischer K, Busch R, et al. Head-to-head comparison of obinutuzumab (GA101) plus chlorambucil (Clb) versus rituximab plus Clb in patients with chronic lymphocytic leukemia (CLL) and co-existing medical conditions (comorbidities): final stage 2 results of the CLL11 trial. Oral presentation presented at: American Society of Hematology (ASH) 2013 Annual Meeting; December 6-10, 2013; New Orleans, LA. Abstract 6.
2. American Society of Hematology. Improved efficacy, limited toxicity of targeted therapies brighten the future of treatment for chronic lymphocytic leukemia. Press release; December 8, 2013. www.hematology.org/news/2013/11772.aspx. Accessed February 2, 2014.