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What Next? Update on Management of Resistant CLL After First-Line Therapy

By: Chase Doyle
Posted: Monday, June 28, 2021

In relapsed chronic lymphocytic leukemia (CLL), the treatment landscape has changed markedly in recent years, mostly because of changes in the first-line setting. According to Jennifer R. Brown, MD, PhD, of Dana-Farber Cancer Institute, Boston, the choice of therapy depends on the risk profile, prior treatments, and patient comorbidities. During the NCCN 2021 Virtual Annual Conference, Dr. Brown discussed appropriate therapy for patients following a relapse from various first-line treatments, focusing on Bruton’s tyrosine kinase (BTK) inhibitors ibrutinib and the BCL2 inhibitor venetoclax. Highlights of this presentation were also published in JNCCN–Journal of the National Comprehensive Cancer Network.

As Dr. Brown explained, ibrutinib was the first targeted therapy studied in the relapsed/refractory setting. Results of the RESONATE trial, which compared ibrutinib and ofatumumab in previously treated patients with CLL who had two to three prior regimens, showed a median progression-free survival of 44 months in the ibrutinib arm in this high-risk population. There are still no head-to-head data comparing ibrutinib with the next-generation BTK inhibitors such as acalabrutinib.

In the MURANO study, Dr. Brown commented that a 5-year follow-up showed a median progression-free survival of 54 months with venetoclax/rituximab versus 17 months with bendamustine/rituximab. The 5-year overall survival also favored the venetoclax arm at 82%.

In addition, a high overall response rate with venetoclax after a BTK inhibitor has been well established, but there is less data on BTK inhibition following venetoclax. High complete response rates and undetectable minimal residual disease (MRD) tend to favor the use of venetoclax/rituximab, she noted. According to Dr. Brown, many patients seem to prefer venetoclax/rituximab because it’s a less expensive, time-limited therapy. “For time-limited therapies, we are very interested in performing studies to learn whether MRD can guide treatment decisions, so patients can stop treatment after achieving MRD negativity instead of having a fixed duration of therapy,” Dr. Brown commented.

Disclosure: For Dr. Brown’s disclosures, visit jnccn.org.



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