Obinutuzumab Improves Outcomes in Chronic Lymphocytic Leukemia

The targeted agent obinutuzumab (GA101) demonstrated a greater than doubling of progression-free survival when added to chemotherapy, compared to chemotherapy alone in elderly patients with chronic lymphocytic leukemia. These results were recently presented at the 2013 annual meeting of the American Society of Clinical Oncology (ASCO).

Chronic lymphocytic leukemia (CLL) is one type of leukemia that originates from immune cells referred to as B-cells. CLL is considered to be a slow-growing leukemia; however, once it has advanced, CLL can ultimately become more aggressive in nature.

Some patients who are diagnosed with early CLL do not even undergo therapy until their disease progresses to a pre-determined point, particularly if the patients are elderly, their disease is very slow-growing and in very early stages, and/or they have other medical conditions that may make treatment more difficult to tolerate.

Standard treatment for CLL ranges, depending upon the disease and patient characteristics. Treatment for CLL has become highly individualized, but may include chemotherapy, either as a single agent or in combination with other agents, a stem cell transplant, radiation, and/or targeted therapy.

Obinutuzumab is an agent that is targeted against the CD20 antigen, which is a protein complex found on the surface of B-cells. Obinutuzumab binds to CD20 and stimulates the immune system to kill the cancer cells, as well as potentially causes some direct cell-killing effects. It is not yet approved by the United States Food and Drug Administration (FDA), but is appears to provide significant anti-cancer activity in CLL as it progresses through clinical trials.

Researchers from Germany recently conducted a clinical trial to evaluate the effectiveness of obinutuzumab in CLL. The trial included 590 patients, 45% of whom were over 75 years of age. Patients had an average of 3 co-morbidities (additional health issues). Patients were treated with either obinutuzumab plus the chemotherapy agent chlorambucil, chlorambucil plus rituxan (another agent targeted against the CD20 antigen, but with some differing properties), or chlorambucil only.

At one year, progression-free survival (survival with no progression of cancer) was 84% for those treated with obinutuzumab/chlorambucil, 63% for those treated with rituximab/ chlorambucil, and 27% for those treated with chlorambucil only.
Overall progression-free survival times were 23 months for those on obinutuzumab/chlorambucil, 15.7 months for those on rituxan/chlorambucil and 10.9 months for those on chlorambucil alone.
Side effects were generally mild with the addition of obinutuzumab, except for more infusion reactions, which tended to occur on the very first infusion of the drug.
Survival data are not yet mature enough to determine survival differences from the different treatment regimens.
The researchers concluded that obinutuzumab in addition to chemotherapy significantly improves progression-free survival compared with chemotherapy alone. Additionally, it appears that obinutuzumab may have greater anti-cancer activity in this disease than rituximab; however, direct comparative trials are necessary to truly determine greater effectiveness of one agent over the other.

Reference: Goede V, et al. Obinutuzumab (GA101) plus chlorambucil (Clb) or rituximab (R) plus Clb versus Clb alone in patients with chronic lymphocytic leukemia (CLL) and preexisting medical conditions (comorbidities): Final stage 1 results of the CLL11 (BO21004) phase III trial”. Proceedings from the 2013 annual meeting of the American Society of Clinical Oncology (ASCO). Abstract 7004.