Venetoclax anti-CD20 monoclonal antibody combination shows promise in CLL

The integration of a fixed-duration regimen of venetoclax and an anti-CD20 monoclonal antibody improved outcomes for patients with chronic lymphocytic leukemia (CLL), according to a special report published in Expert Review of Anticancer Therapy. Although Bruton's tyrosine kinase inhibitors (BTKi) are superior to chemoimmunotherapy, some patients acquire BTK mutations that render them resistant to BTKi. This has drawn attention to the advantages of venetoclax, particularly in combination with anti-CD20 monoclonal antibodies as a time-limited therapy.

Two landmark studiesMURANO and CLL14 were designed to evaluate the long-term effects of this combination therapy in patients with CLL. The MURANO trial enrolled 389 patients with relapsed/refractory CLL who were randomized to receive either venetoclax plus rituximab or bendamustine plus rituximab. This 7-year study found that the median progression-free survival of patients in the first group was significantly higher than that of patients in the second group (54.7 months vs. 17.0 months). In addition, the 7-year overall survival rate of patients randomized to receive venetoclax/rituximab combination treatment was 69.6%, while the overall survival rate of patients treated with bendamustine/rituximab during the same period was 51.0%.

A substudy of the MURANO trial treated patients (n=25) with progressive disease in either arm with the venetoclax/rituximab combination. Of these 25 patients, 14 (56.0%) achieved undetectable minimal residual disease at the end of the study. The CLL14 trial enrolled 432 patients with previously untreated CLL who were ineligible for intensive chemoimmunotherapy due to advanced disease/renal impairment. Participants were randomized to receive either venetoclax plus obinutuzumab or chlorambucil plus obinutuzumab.

The 6-year study found that the median progression-free survival was 76.2 months in the first group and 36.4 months in the second group. In addition, the 6-year overall survival rate of patients randomized to receive venetoclax/obinutuzumab combination therapy was 78.7%, while the overall survival rate of patients treated with chlorambucil/obinutuzumab during the same period was 69.2%. Long-term results from the MURANO and CLL14 trials clearly establish the breakthrough role of the (fixed-duration) venetoclax/anti-CD20 (monoclonal antibody) combination in the treatment of (treatment-naïve) and (relapsed/refractory) CLL.