Jacob Soumerai, MD

Jacob Soumerai, MD, Assistant Professor at Harvard Medical School and Massachusetts General Hospital Cancer Center, who was not involved in this study, commented on the MURANO study findings.

“MURANO is the definitive phase III trial that established venetoclax/rituximab as a standard of care for the treatment of relapsed or refractory chronic lymphocytic leukemia [CLL]. Venetoclax/rituximab was associated with improved progression-free and overall survival compared with bendamustine/rituximab,” he noted. “In this study, time-limited venetoclax/rituximab was given, and the authors updated long-term progression-free and overall survival and explored outcomes after treatment discontinuation among patients achieving undetectable minimal residual disease [MRD].”

Median progression-free survival at 5 years was 53.6 months with venetoclax/rituximab vs 17 months with bendamustine/rituximab. An estimated 5-year overall survival was 82.1% vs 62.2%, respectively.

“This presentation was a deeper dive into the population of patients achieving undetectable MRD at the end of treatment. Among these patients, 61% remained free of disease progression at 36 months from the end of treatment. The authors found that undetectable MRD was strongly predictive of progression-free survival,” Dr. Soumerai said.

“These data are helpful for counseling patients. When patients achieve undetectable MRD at the end of therapy, the median time until conversion to detectable MRD is about 19 months. Following conversion to detectable MRD, the median time until clinical disease progression is another 24 months. Of note, there might be an MRD plateau emerging, which raises the possibility that the risk of conversion to MRD is reduced over time in these patients,” he continued.

Baseline Factors and Outcomes

“The authors next assessed whether any baseline factors might predict outcomes. There were just four patients with del(17p) who achieved MRD, all of whom experienced disease progression after completing therapy. The numbers are too small to provide clarity on the optimal management of patients with del(17p), ie, whether time-limited therapy is the best approach for these patients,” Dr. Soumerai noted.

“The authors also looked at baseline genetic risk factors and the rate of growth in MRD after stopping therapy. Three risk factors—del(17p), genetic complexity, and IGHV status—were associated with a higher risk of disease progression as well as a more rapid growth rate in MRD,” he said.

Dr. Soumerai continued: “These data confirm the feasibility of a time-limited venetoclax/rituximab regimen with durable control of CLL after discontinuation of therapy. What is most interesting is that the authors have identified pretreatment CLL genetic characteristics that appear to be associated with growth rate and clinical disease progression after treatment discontinuation. These data will inform future trials in this space.” 

DISCLOSURE: Dr. Soumerai has served as a consultant or advisor to AbbVie, AstraZeneca, and Verastem and has received research funding from BeiGene, BostonGene, Genentech/Roche, and TG Therapeutics.