Venetoclax, Anti-CD20 Monoclonal Antibody Combination Shows Promise in CLL 

The integration of venetoclax and anti-CD20 monoclonal antibody fixed-duration regimens improves outcomes in patients with chronic lymphocytic leukemia (CLL), according to a special report published in the Expert Review of Anticancer Therapy. 

Despite the superiority of Bruton’s tyrosine kinase inhibitors (BTKi) over chemo-immunotherapy, some patients acquire BTK mutations that make them resistant to BTKi. This has led to attention towards investigating the merits of venetoclax, especially in combination with an anti-CD20 monoclonal antibody as a time-limited therapy. 

Two landmark studies, the MURANO and the CLL14, were designed to assess the long-term impact of this combination therapy in patients with CLL.

The MURANO trial involved 389 patients with relapsed/refractory CLL who were randomized to either receive venetoclax with rituximab, or bendamustine and rituximab. This 7-year study found that patients in the first group had a significantly higher median progression-free survival compared with those in the second (54.7 months vs 17.0 months). In addition, those randomized to receive the combination of venetoclax/rituximab had a 7-year overall survival of 69.6%, while those who received bendamustine/rituximab had an overall survival of 51.0% during the same period. 

A sub-study of the MURANO trial was opened for patients who developed progressive disease in either group (n=25) to receive venetoclax/rituximab combination therapy. Among these 25 patients, 14 (56.0%) achieved undetectable minimal residual disease at the end of the study. 

The CLL14 trial involved 432 treatment-naïve patients with CLL who were unsuited for intensive chemo-immunotherapy due to advanced disease/renal impairment. Participants were randomized to either receive venetoclax with obinutuzumab, or chlorambucil with obinutuzumab. 

This 6-year study found that median progression-free survival was 76.2 months in the first cohort compared to 36.4 months in the second. In addition, those randomized to receive the combination of venetoclax/obinutuzumab had a six-year overall survival of 78.7%, while those who received chlorambucil/obinutuzumab had an overall survival of 69.2% during the same period. 

“The long-term results of the MURANO and CLL14 trials…have definitively established the role of [fixed-duration] venetoclax/anti-CD20 [monoclonal antibody] combinations as a breakthrough in the treatment of both [treatment-naïve] and [relapsed/refractory] CLL,” the authors wrote in their report. 

This article originally appeared on Hematology Advisor