February 2014, Vol 3, No 1
Novel Anti-CD20 Antibody Superior to Rituximab on Progression-Free Survival in Unfit CLL Patients
Obinutuzumab, a novel, glycoengineered, type II CD20 antibody, in combination with chlorambucil was superior to rituximab plus chlorambucil in prolonging progression-free survival (PFS) in previously untreated patients with chronic lymphocytic leukemia (CLL) with comorbidities.
Treatment with obinutuzumab also led to a significantly higher objective response rate, and more patients treated with obinutuzumab were negative for minimal residual disease (MRD) in the bone marrow and blood, announced Valentin Goede, MD, hematologist/oncologist at the Center for Integrated Oncology, University Hospital Cologne, Germany.
On November 1, 2013, the FDA approved obinutuzÂumab for use in combination with chlorambucil for the treatment of patients with previously untreated CLL.
The findings âmean a significant and potentially practice-changing treatment advance for this large patient population,â said Goede. âWhat we currently know is if we combine obinutuzumab or rituximab with a weaker chemotherapy backbone, obinutuzumab is obviously superior to rituximab, so in this setting I would say that it will substitute for rituximab…at least in the population of elderly patients.â
In CLL11, 781 patients with CLL complicated by comorbidities were randomized to 1 of 3 first-line regimens: chlorambucil alone, chlorambucil plus rituximab, or chlorambucil plus obinutuzumab. To be eligible for the trial, patients had to have a total Cumulative Illness Rating Scale score >6 and/or creatinine clearance <70 mL/min.
Results from the first stage of the trial were reported previously and showed that obinutuzumab/chlorambucil and rituximab/chlorambucil were each associated with significantly better PFS compared with chlorambucil alone.
Updated results from stage I were reported here. Compared with chlorambucil alone, the risk of disease progression or death was improved by 82% with obinutuzumab (P<.0001). The median PFS was 26.7 months with the combination. Rituximab plus chlorambucil produced a 66% reduction in the risk of progression or death, and a 16.3-month median PFS. Overall survival was also superior with obinutuzÂumab, with a hazard ratio for death of 0.41 (P=.0022).
In the second-stage analysis, a head-to-head comparison of the 2 combination regimens was conducted. In this comparison, the median PFS with obinutuzumab plus chlorÂambucil was 11.5 months greater than with rituximab plus chlorambucil (26.7 vs 15.2 months), corresponding to a 61% reduction in risk by adding obinutuzumab instead of rituximab (P<.0001).
Complete responses were achieved in 21% of the obinutuzumab arm versus 7% of the rituximab arm. The overall response rates were 78% with obinutuzumab and 65% with rituximab (P<.0001).
Some 19.5% of patients in the obinutuzumab arm were MRD negative for bone marrow versus 2.6% in the rituximab group (P<.0001). MRD was negative in blood in 37.7% of the obinutuzumab arm versus 3.3% in the rituximab arm.
After a median follow-up of approximately 19 months, survival favors obinutuzumab in the head-to-head comparison with rituximab (P=.0849), although the data for survival remain immature, with fewer than 15% of events included in the analysis, Goede said.
There were more grade ?3 adverse events with obinutuzumab/chlorambucil than with rituximab/chlorÂambucil (70% vs 55%). Infusion-related reactions (20% vs 4%) and thrombocytopenia (10% vs 3%) were more frequent in the obinutuzumab arm.
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