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Comparison of Venetoclax-Based Treatments for CLL

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Medically reviewed by Dr. Brian Koffman

The Bottom Line:

Venetoclax-based combination therapies lead to durable remissions in patients with high-risk relapsed / refractory CLL.

Who Performed the Research and Where Was it Presented:

Dr. Benjamin Heyman from Moores Cancer Center at the University of California San Diego and colleagues presented the results at the American Society for Hematology (ASH) Annual Meeting 2023.


Venetoclax is a BCL2 inhibitor that is very effective in treating chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). Several different treatment regimens use venetoclax. The current venetoclax-based treatments that are FDA-approved for relapsed / refractory CLL are venetoclax monotherapy and the combination of venetoclax plus rituximab. Venetoclax, in combination with obinutuzumab, is approved for previously untreated CLL /SLL, and ventoclax plus Bruton tyrosine kinase inhibitors (BTKi) is being used in clinical trials and off-label. This study aimed to compare the efficacy of these different venetoclax-based treatments using clinical practice data.

Methods and Participants:

This was a retrospective study using clinical data from UC San Diego. It included patients with relapsed / refractory CLL who were treated with venetoclax-based therapies between 2012 and 2023. Treatments included: 1) venetoclax monotherapy, 2) venetoclax + rituximab, 3) venetoclax + obinutuzumab, and 4) venetoclax + BTKi.


  • 98 patients were evaluated, with a median follow-up time of a little over four years.
  • Most patients had high-risk disease, including 50% with advanced Rai stage, 70% with unmutated IgVH, 25% with deletion 17p or TP53 mutation, and 26% with ≥ 5 gene mutations.
  • Venetoclax-based combination therapies resulted in significantly longer progression-free survival (77 months) than venetoclax monotherapy (59 months).
  • While not statistically significant, there was a trend for improved progression-free survival with venetoclax + obinutuzumab and venetoclax + BTKi compared with venetoclax + rituximab.
  • All regimens produced good rates of undetectable measurable residual disease (uMRD), ranging from 65% to 85% of patients.
  • Patients with deletion 17p or TP53 mutations had shorter times in remission, irrespective of the type of treatment.
  • Patients who maintained uMRD one year after stopping fixed-duration therapy had excellent long-term outcomes.


Venetoclax-based combination therapies lead to durable remissions and high rates of uMRD in patients with high-risk relapsed / refractory CLL. Venetoclax plus obinutuzumab and venetoclax plus ibrutinib are effective as frontline treatments for CLL, and these results show that they work in relapsed / refractory disease as well. Several other venetoclax-based combination therapies continue to be tested in clinical trials, including venetoclax + acalabrutinib and triple combination venetoclax + obinutuzumab with either acalabrutinib or zanubrutinib. There continues to be significant interest in venetoclax-based treatments due to their efficacy and benefit as fixed-duration therapies.

Links and Resources:

Watch the interview on the abstract here:

Comparison of Venetoclax-Based Treatments for CLL – Dr. Benjamin Heyman ASH 2023

You can read the actual ASH abstract here: Comparison of Venetoclax Based Treatments for Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia

Take care of yourself first.

Ann Liu, PhD