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The phase III CLL11 study examined obinutuzumab plus chlorambucil in patients with chronic lymphocytic leukemia (CLL) who were considered unfit, defined as a Cumulative Illness Rating Scale (CIRS) score of >6 or an estimated creatinine clearance of <70 mL per minute. Patients were randomized into 3 study arms: chlorambucil alone, rituximab plus chlorambucil, and obinutuzumab plus chlorambucil.
The results showed that both combination arms were superior to chlorambucil monotherapy in terms of response rate, progression-free survival (PFS), and overall survival, explains Shuo Ma, MD, PhD. Between the combination arms, there was improved PFS with obinutuzumab, but there was no overall survival benefit. The median PFS was 26.7 months with obinutuzumab plus chlorambucil compared with 14.9 months with rituximab and chlorambucil (HR = 0.42; 95% CI, 0.33-0.54; P
Another striking result was the higher rate of complete response (CR) and MRD-negative complete response achieved with the obinutuzumab combination. The CR rate with obinutuzumab was 26.1% compared with 8.8% with rituximab. In peripheral blood, 41% of patients treated with obinutuzumab were MRD negative compared with 12% with rituximab.
The side effects associated with obinutuzumab include a significant infusional toxicity with the first dose, Myron Czuczman, MD, warns. He recommends that patients be pre-medicated with glucocorticoids, and also be prepared to manage that toxicity. Although the obinutuzumab/chlorambucil regimen has primarily been used with older unfit patients, administration of the combination in younger patients is increasing.
Other combinations, such as bendamustine and obinutuzumab, are also being tested in younger patients. At this point, Thomas J. Kipps, MD, notes that results with these combinations are very good.