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ASCO 2020 Top 12” #9: Impact of premature venetoclax (Ven) discontinuation/interruption on outcomes in relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL): Phase III MURANO study results

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In short videos with accompanying text, Dr. Brian Koffman, the Executive Vice President (EVP) and Chief Medical Officer (CMO) of the CLL Society, takes us through his “Top 12” abstracts from ASCO or the American Society of Clinical Oncology Annual Meeting held virtually in May, 2020.

#9

ASCO 2020: Impact of premature venetoclax (Ven) discontinuation/interruption on outcomes in relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL): Phase III MURANO study results

The MURANO trial of the combination of venetoclax + rituximab (VenR) proved its clear superiority to bendamustine and rituximab (BR) and led to its game changing approval in relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL).

We know well that venetoclax + rituximab (VenR) is generally well tolerated and improves survival in relapsed/refractory chronic lymphocytic leukemia patients, but discontinuations and dose interruptions are frequent.

This study, led by Dr. Anthony Mato, assesses whether early discontinuation of venetoclax before the recommended 2 year course of treatment is completed makes a difference.

Takeaways:

  • 140/194 pts (72%) in the VenR arm completed the prescribed 2 years of therapy, but 54 or 28% quit early.
  • The reasons for the 54 who quit were:
    • adverse events [AEs]: 29
    • disease progression [PD]: 12
    • withdrawal: 5
    • physician decision: 3
    • death: 2
    • other: 2
    • non-compliance: 1
  • The average length of time on venetoclax for those who came off due to adverse events (AEs) was 11 months.
  • Those whose disease progressed (PD) stopped on average at 17 months.
  • The researchers excluded from the statistical analysis those who went off the VenR due to PD. Those patients would obviously do worse, so it would not be fair to compare them to those who completed the full 2 years.
  • The data showed that stopping the venetoclax for any other reason besides PD before the 2 years was associated with significantly poorer outcomes and shorter progression free survival (PFS).
  • The longer patients were on venetoclax, the longer was their PFS.
  • The good news is that even though 69% of patients had to interrupt daily venetoclax due to AEs, even lengthy interruptions were not associated with a worse outcome as long as patients completed the full two years of therapy. The most common reason for holding venetoclax was low neutrophils.

Conclusions:

Meds don’t work if you don’t take them. And it seems with venetoclax, the more you take, at least for up to two years, the better, even if the dosing has lengthy interruptions. That makes a strong case for being in the care of experts who can help manage side effects and hopefully get patients through a complete course of therapy. The fact that gaps in treatment can be made up by adding the missed time on meds to the end of the treatment cycle is reassuring and, for me, hints that the more you take, the deeper down you drive the cancer.

How these findings tie in with treating to uMRD (undetectable minimal or measurable residual disease) is a whole other question that future research will explore.

For now, this is mostly good news because most patients do finish their meds, and many who in the past might have stopped prematurely, now know that it is better to pause and then restart venetoclax in order to finish therapy, rather than to stop venetoclax.

Here is the link to Impact of premature venetoclax (Ven) discontinuation/interruption on outcomes in relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL): Phase III MURANO study results

Stay strong.  We are all in this together.

Brian

Brian Koffman MDCM (retired) MS Ed

Co-Founder, Executive VP and Chief Medical Officer
CLL Society, Inc.

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