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Response to CLL Therapies After Fixed-Duration Venetoclax

In science and medicine, information is constantly changing and may become out-of-date as new data emerge. All articles and interviews are informational only, should never be considered medical advice, and should never be acted on without review with your health care team.

Medically reviewed by Dr. Brian Koffman

The Bottom Line:

After fixed-duration venetoclax plus rituximab, both BTK inhibitors and retreatment with venetoclax are viable options for treating relapsed CLL.

Who Performed the Research and Where Was it Presented:

Dr. John Seymour from Peter MacCallum Cancer Center and colleagues presented the results at the American Society for Hematology (ASH) Annual Meeting 2023.


While therapies for chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) have improved substantially in the last decade, they are not curative, and patients often relapse. Two significant questions in CLL / SLL treatment are 1) How should therapies be sequenced, and 2) Can patients be retreated with the same drug? Dr. Seymour and colleagues used data from the MURANO trial to try to answer these questions.

Methods and Participants:

The MURANO trial was a phase 3 clinical trial that compared fixed-duration venetoclax plus rituximab with bendamustine plus rituximab in patients with relapsed / refractory CLL. In total, 389 patients were enrolled in the study. Patients were monitored for progressive disease and their response to any subsequent therapies.


  • The median follow-up time for patients in this study was seven years.
  • Among patients who received venetoclax + rituximab, 30 patients were subsequently treated with a BTK inhibitor due to progressive disease.
  • For this group, 86% responded to treatment; the median time to progression on BTK inhibitor was 42 months (about 3.5 years).
  • In this study, 42 patients responded well to their initial venetoclax + rituximab treatment, had time off treatment, and then were retreated with venetoclax due to progressive disease.
  • This group’s median time off treatment was 30 months (about 2.5 years).
  • 76% of patients responded to retreatment, and the median time to progression was 59 months (almost five years).
  • Among patients initially treated with bendamustine + rituximab and then needing subsequent therapy due to progressive disease, 80% responded to BTK inhibitors, and 90% responded to venetoclax.
  • However, despite reasonable response rates, overall survival at five years was 20% lower in the bendamustine + rituximab group compared with the venetoclax + rituximab group.


This study shows that BTK inhibitors and venetoclax retreatment are viable options for treating relapsed CLL after fixed-duration venetoclax plus rituximab. Patients should remember that reemergent disease does not necessarily mean resistant/refractory disease when fixed-duration treatments are used.

Additionally, since this study was done, other clinical trials have shown that venetoclax plus obinutuzimab is more effective than venetoclax plus rituximab. Targeted therapies are now clearly preferred over chemoimmunotherapy, and while they can still be used after chemoimmunotherapy, it is preferable to begin targeted therapies as early as possible.

Links and Resources:

Watch the interview on the abstract here:

Response to CLL Therapies After Fixed-Duration Venetoclax – ASH 2023 Dr. John Seymour

You can read the actual ASH abstract here: Response to Subsequent Novel Therapies and Time to Second Progression-Free Survival Event in the MURANO Trial in Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia Previously Treated with Fixed-Dose Venetoclax Plus Rituximab.

Take care of yourself first.

Ann Liu, PhD