Results of Phase II Study of Combination Obinutuzumab, Ibrutinib, and Venetoclax in Treatment-Naïve and Relapsed or Refractory CLL

[Jm954]

I think the most surprising thing in this report is that not everyone responds - "The overall response rate at that time was 84% in treatment-naïve patients and 88% in relapsed or refractory patients."

A short report here: ascopubs.org/doi/full/10.12...

Jackie

[cajunjeff]

You would think particularly in the treatment naive cohort there would be an almost 100% at least partial response to this combination.

It is worth noting that between the two 25 person cohorts, only one person progressed with their disease and one died (although its not clear what the cause of death was from this blurb).

I dont think overall response rate includes those who do not progress and have stable disease. So at least it appears there is still benefit from the drugs to even those who do not have some overall response. In two years of follow up only one person progressed, so overall still a very hopeful study.

So to put a more happy face on the report of the phase two trial, 48 out of 50 benefitted from the combination with only one person progressing and a second dying of some cause that is not clear, at least in this report.

At the age most of us are when we are diagnosed with cll, if you pick any random group of fifty people one or two might not make it two years out.

Its a very promising study, realistically we know at this point not every treatment will work for everyone of us. 88% ORR in the relapsed group is impressive, higher than the treatment naive group. I think the treatment naive group will fare a lot better than the relapsed group in a larger study. This is a small sample size for both groups.

[cllady01 Former Volunteer]

When it is said that a Phase III trial is being run in "cooperative group tasks" is that clinical experiences? And, is that also a way for clinicians to be the ones testing by lowering or temporarily stopping one or more of the meds---giving data, then that might not be available from the Phase II trial?

[Jm954 Administrator in reply to cllady01]

I honestly don’t know the answer to that but this combination is now running in several phase III trials, mainly USA.

[Smith123456 in reply to Jm954]

I take all 3 in usa. I am not on a trial. I finished 6 months of gazyva last month

[NaturalWaze in reply to Smith123456]

I did not know you could take all 3 in the US. I thought it’s only in trials??? (It was offered to me in a randomized trial.) Did your CLL specialist give it to you?

[Smakwater in reply to NaturalWaze]

All three drugs are approved for use in CLL. The combinations not yet established.

[Smith123456 in reply to NaturalWaze]

if your willing to pay the co-pays all is possible in usa, after awhile i figured out ways to get 2/3 of the bills paid. for it. Was also not a planned sequence,

started imbruvica January 2019, added venclexta december 2019, started gazyva may 2020 and last dose oct 2020.. still on imbruvica /venclexta.

[NaturalWaze in reply to Smith123456]

Ok, got it... thanks for the explanation, and good luck to you!

[cllady01 Former Volunteer in reply to Jm954]

I just now found this that may help define Cooperative Group Tasks----But, I can't explain it beyond assessments?

deainfo.nci.nih.gov/advisor...

[johnl]

When they say a median follow up of 24.2 months, do they mean from they end of the trial or from the start of the trial ?

By the way, glad to see you made it thru the hurricanes Jeff.

john

[Jm954 Administrator in reply to johnl]

It means that the average follow up period was 24.2 months from the start of treatment.

[bkoffman CLL CURE Hero]

Response rates are nice. Overall response (OS) rate is what really counts . For that you have to wait. How we sequence drugs, which combos and when, is the research we need, but won't get from PHRMA. It's a chess game. No-one resigns or checkmates immediately after opening pawn to king's 4,. It's the following moves that determines if you are a winner.

[Awksom in reply to bkoffman]

I like your chess analogy.

[Jm954 Administrator in reply to bkoffman]

OS rates were quoted

[bkoffman CLL CURE Hero in reply to Jm954]

Thanks. OS doesn't mean much until you are years out with an indolent cancer. But I do appreciate seeing the early trends.

[Smith123456 in reply to bkoffman]

i am a mediocre chess player. Oh well.

[bkoffman CLL CURE Hero in reply to Smith123456]

But you know the principles and appreciate a master.

[Smith123456 in reply to bkoffman]

That's you

[avzuclav in reply to bkoffman]

OS looking good with the three-year update to this study at ASH 2020.

"The medians for PFS and OS were not reached (Figure 1). The 36- month estimated PFS is 95% (95% CI: 72-99%) for TN and 95% (95% CI: 69-99%) for RR patients. The 36-month estimated OS is 95% (95% CI: 72-99) for TN and 100% for RR patients."

Three-Year Follow-up from a Phase 2 Study of Combination Obinutuzumab, Ibrutinib, and Venetoclax in Chronic Lymphocytic Leukemia

ashpublications.org/blood/a...

[Jm954 Administrator in reply to avzuclav]

Excellent, thanks for that

Jackie