February 2014, Vol 3, No 1

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Novel Anti-CD20 Antibody Superior to Rituximab on Progression-Free Survival in Unfit CLL Patients

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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 obinutuz­umab for use in combination with chlorambucil for the treatment of patients with previously untreated CLL.

The findings “mean a significant and potentially practice-changing treatment advance for this large patient population,” said Goede. “What 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.”

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 obinutuz­umab, 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 chlor­ambucil 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/chlor­ambucil (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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Letter to Our Readers - February 21, 2014

The Importance of the Multidisciplinary Team in Personalizing Care

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