Venetoclax plus Rituxmab for CLL - four year data

I recently shared the six year follow-up data for one of the first Ibrutinib studies. Today to keep it balanced, I will discuss the recent four year data of the Venetoclax Rituximab combo (VR). Both these options are available to all patients in the UK under NICE funding as an option to consider for second line treatment (i.e. when they have had previous treatments)

I will compare the data a little and stick to a bullet type format. But you should be aware that the patient groups are different and so you can’t directly compare these two sets of data and shouldn’t read too much into it.

It remains the case that both options seem to be reasonable as treatment choices at all stages of the illness You may want to also have a look at the original study if you have not seen it and I will refer to it here also

Four Year Data (released just before Christmas)

https://ashpublications.org/blood/article/134/Supplement_1/355/426130/Four-Year-Analysis-of-Murano-Study-Confirms

Original study

https://www.nejm.org/doi/full/10.1056/NEJMoa1713976

Key Points

  • Population: About a quarter of the patients had a 17p deletion. About a quarter had TP53 mutation and around 70% were unmutated. And they were all patients who had relapsed after previously receiving between 1 and 3 treatments (this is LESS treatments than some patients in the Ibrutinib study had received). A more recent study has also been reported using a combo with V plus obinituximab for untreated patients.

  • A HUGE 86% of those randomised to VR had not shown disease progression at two years. This compared to just 36% in the comparator group.

  • Figure 3 in the original paper shows venetoclax still worked in all the different sub groups you can imagine.

-Remarkably a full quarter of the patients stopped the venetoclax early and so therefore clearly some of them still got benefit from it despite shorter use.

-This was a fixed-term 2 years of Venetoclax with 6 months of rituximab.

At four years post treatment initiation (two years since stopping)

  • 57% of the Venetoclax/Rituximab treated group had not had progression of their CLL (only 4.6% of the comparator BR chemo group had not progressed)

-In comparison after four years of continuous ibrutinib treatment more than half had shown progression (rememberer, however that study had perhaps a sicker cohort than the venetoclax one)

-By the end of treatment, 64% of VR patients had achieved MRD-negativity / undetectable status, and of those patients 87% remained free of disease progression two years post-treatment.

-85.3% of venetoclax patients were still alive after four years vs 66.8% of the BR patients (even though many of the second group were later able to take selective treatments after the study)

-14 patients from the venetoclax group as so far been re-treated with venetoclax after subsequent relapse but most of those they have not yet got response data for (presumably treatment is ongoing). This will be a group to watch of course, to see if repeat treatment is as good as initial treatment or not.

  • Perhaps most encouraging of all is the text shown in the photo attached which is not discussed in detail in the paper. But here we can see unrefutable evidence that just like with chemo therapy before it those who get to MRD-U with a venetoclax combo can be confident that they have a great chance of remaining well. Many more people got to undetectable status with venetoclax than with BR chemo.
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Thanks again Adrian for all this data and taking the time to post it with the key points as well.