Disappearance of B-Symptoms In Comorbid Patients Receiving First-Line Obinutuzumab (Ga101) -Chlorambucil (G-Clb) Or Rituximab-Chlorambucil (R-Clb) for Chronic Lymphocytic Leukemia (Cll)

The CLL11 study (stage 2, NCT02053610; sponsored by F. Hoffmann-La Roche, Basel, Switzerland), compared G-Clb with R-Clb in 663 patients with previously untreated CLL and comorbidities. We compared the presence, disappearance and duration of absence of B-symptoms (fever, night sweats and weight loss) for G-Clb with R-Clb in CLL11. Patients were randomised to receive six 28-day (D) cycles (C) of G-Clb (N=333) or R-Clb (N=330; G: 1000 mg D1,8 and 15 C1, D1C2–6; R: 375 mg/m2 D1C1,500 mg/m2 D1C2–6; Clb: 0.5 mg/kg D1 and 15 each cycle). B-symptoms were assessed by a physician at baseline, D1C1, D8C1, D1 of each subsequent cycle, 28 days after last study drug and every 3–6 months during follow-up for progression-free survival. The data cut-off for this analysis was 9thMay 2013. At baseline, 260 patients had B-symptoms (n=126, G-Clb; n=134, R-Clb). During the treatment period, B-symptoms disappeared in 107 (85%) and 124 (93%) patients who received G-Clb and R-Clb, respectively (relative risk [RR]: 0.92,95% confidence interval [CI]: 0.84–1.00; p=0.0554). Median time to first disappearance of all B-symptoms was 32.0 days for G-Clb and 35.0 days for R-Clb (hazard ratio [HR]: 1.24,95% CI: 0.96–1.61; p=0.103). At end of treatment, 96 (76%) and 108 (81%) patients who received G-Clb and R-Clb, respectively, were B-symptom free (RR: 0.95,95% CI: 0.83–1.07; p=0.3899). In patients whose B-symptoms disappeared, the 25% quartile for duration of absence of B-symptoms (median not reached) was 16.4 months for G-Clb and 10.4 months for R-Clb (HR: 0.59,95% CI: 0.36–0.97; p=0.0387). There was no clinically meaningful difference in B-symptom freeness at end of treatment, however the absence of B-symptoms was prolonged by 6 months for G-Clb versus R-Clb.