Obinutuzumab/Chlorambucil Superior to Rituximab/Chlorambucil as First-Line Treatment for Older CLL Patients With Comorbidities


Key Points

  • Obinutuzumab/chlorambucil was superior to rituximab/chlorambucil in an older chronic lymphocytic leukemia population with comorbidities.
  • Obinutuzumab/chlorambucil prolonged survival, progression-free survival, and eradicated minimal residual disease more often than rituximab/chlorambucil.
  • The results suggest that obinutuzumab can replace rituximab when combined with chlorambucil as first-line treatment for older, sicker CLL patients.

Obinutuzumab (Gazyva) plus chlorambucil (Leukeran) was superior to rituximab (Rituximab) plus chlorambucil as first-line therapy in older chronic lymphocytic leukemia (CLL) patients with comorbidities, with an acceptable safety profile, according to final results of the phase III CLL11 trial. Obinutuzumab/chlorambucil led to a prolongation in overall survival, as well as improved progression-free survival, complete response rate, and minimal residual disease–negative status. The results were presented today during a Plenary Session at the 55th American Society of Hematology (ASH) Annual Meeting and Exposition (Abstract 6).

“These results suggest that obinutuzumab can replace rituximab in combination with chlorambucil as first-line therapy in the specific population studied—ie, older patients with comorbidities. This would mean a potential decrease in the amount of chemotherapy required for an effective combination regimen, translating to less toxicity for patients,” said Valentin Goede, MD, of University Hospital Cologne, Cologne, Germany.

“These findings are significant and potentially practice-changing for this large patient population of older CLL patients with comorbidities,” he stated at a press conference.

Obinutuzumab is an anti-CD20 antibody that appears to be more potent than the anti-CD20 antibody rituximab, a current standard of care.

Head-to-Head Comparison

The study enrolled 781 patients and randomly assigned them in a 2:1:2 ratio to three arms: obinutuzumab/chlorambucil for six cycles; chlorambucil for six cycles (control); or rituximab/chlorambucil for six cycles. Dr. Goede presented the results of the head-to-head comparison between obinutuzumab/chlorambucil and rituximab/chlorambucil.

Obinutuzmab/chlorambucil was associated with more grade 4 or higher adverse events, mainly infusion-related reactions that occur during the first infusion: 20% in patients treated with obinutuzumab/chlorambucil vs 4% with rituximab/chlorambucil. “Now we are vigilant about preventing these reactions to increase safety,” Dr. Goede said. No increased risk of infection was observed with obinutuzumab/chlorambucil.

Superior Progression-Free Survival and Response Rates With Obinutuzumab

Overall response rate was higher with obinutuzumab/chlorambucil vs rituximab/chlorambucil: 78% vs 68%. Obinutuzumab/chlorambucil was also superior in eradicating detectable disease in the bone marrow and in blood; the rate of minimal residual disease–negative status in bone marrow was 19.5% for obinutuzumab/chlorambucil vs 2.6% for rituximab/chlorambucil (P < .0001), and minimal residual disease–negative status in blood was observed in 37.3% vs 3.3% of patients, respectively (P < .0001).

For the primary endpoint, obinutuzumab/chlorambucil led to a 61% improvement in the likelihood of achieving progression-free survival. Median progression-free survival was 26.7 months vs 15.2 months, respectively (P < .0001).

Overall survival data are not yet mature, but at present obinutuzumab/chlorambucil appears to be significantly better than rituximab/chlorambucil, Dr. Goede noted.

For full disclosures of the study authors, view the study abstract on the ASH website.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.