Obinutuzumab Superior to Rituximab in Older Patients with CLL

New Orleans—In a head-to-head phase 3 trial, older patients with previously untreated chronic lymphocytic leukemia (CLL) and comorbidities had a significant increase in median progression-free survival and a higher response rate if they were randomized to receive obinutuzumab plus chemotherapy compared with a group taking rituximab plus chemotherapy.

The median progression-free survival was 26.7 months in the obinutuzumab group and 15.2 months in the rituximab group (hazard ratio [HR], 0.39; 95% confidence interval, 0.31-0.49; P<.0001). Valentin Goede, MD, lead author of the study and an oncologist and geriatrician, noted the progression-free survival benefit favoring obinutuzumab was found in all pre-planned subgroup analyses. The combination of rituximab and chemotherapy is the standard of care first-line treatment for these patients.

“This means a potentially practice changing treatment advance for this large patient population,” said Dr. Goede during a plenary session at the ASH meeting where the study results were presented.

In November, the FDA approved obinutuzumab in combination with chlorambucil for previously untreated CLL. The injectable drug, an anti-CD20 monoclonal antibody and targeted therapy administered via intravenous infusion, is the first medication approved with the FDA’s breakthrough designation for medications intended for serious or life-threatening conditions. The FDA also granted obinutuzumab an orphan product designation because it is intended to treat a rare disease, which is defined as having a prevalence <200,000 people in the United States. According to Roche, the manufacturer of obinutuzumab, CLL is the most common type of leukemia in the Western hemisphere and causes 75,000 deaths worldwide each year.

In this open-label study, the authors randomized 781 patients in a 2:1:2 ratio to receive 6 cycles of obinutuzumab plus chlorambucil (n=333), chlorambucil alone (n=118), or rituximab plus chlorambucil (n=330). Patients were required to have a Cumulative Illness Rating Scale score >6 and/or a creatinine clearance <70 mL/min.

The trial was sponsored by Roche and the German CLL Study Group, an independent nonprofit research organization that has run early-, mid-, and late-stage CLL trials since 1996.

The obinutuzumab and rituximab groups were well balanced. Approximately 61% of patients were male, and the mean age was 73 years. Common comorbidities were hypertension, coronary heart disease, chronic obstructive pulmonary disease, diabetes, and hyperlipidemia.

The overall response rate was 78% in the obinutuzumab group and 65% in the rituximab group, while the complete response rate was 21% and 7%, respectively.

Grade 3 to 5 adverse events were found in 66% of patients receiving obinutuzumab and 47% of patients taking rituximab. The main difference was in infusion-related reactions: 20% and 4% of patients, respectively. Dr. Goede mentioned that all of the reactions occurred during the first infusion, and none of the reactions were fatal.

Dr. Goede also said that the median progression-free survival in patients taking chlorambucil alone was 11.1 months, which was significantly shorter than the obinutuzumab plus chlorambucil group (HR, 0.18) or the rituximab plus chlorambucil group (HR, 0.44).

There was no difference in overall survival between the chlorambucil alone and rituximab plus chlorambucil groups, while there was an overall survival benefit in obinutuzumab plus chlorambucil versus chlorambucil alone. However, the overall survival data comparing obinutuzumab with rituximab was immature, according to Dr. Goede. Early results favor obinutuzumab (HR, 0.66; P=.08).

“For the future, [the goal of treatment of these patients] may expand from pure simple control to long-lasting disease control,” Dr. Goede said.