Test Before Treat?

[JustAGuy]

I recall from last year's ASH conference several of the experts saying "test before treat". I understand that this was to make sure the treatment matched the cytogenetics of one's CLL.

How does this apply to O + V treatment, it seems so standard now. With this treatment is there the same need for testing?

[cllady01 Former Volunteer]

cllsociety.org/2019/11/expe...

You can get several CLL expert opinions from this one link.

[AussieNeil Administrator]

You are right that the primary focus of TestB4Treat is to ensure that those who are unlikely to do well on chemoimmunotherapy are treated with a targeted therapy. However, knowing that someone has a complex karyotype from their FISH test seems to be steering towards BTK maintenance therapy rather than fixed term therapy (V+O). (I don't know that we know whether fixed term therapy (V+O) or a maintenance BTKi is the better option yet for TP53 mutated/deleted.) So TestB4Treat in the UK is still valid, even when V+O has become the new standard first line treatment.

Importantly, having this test result information available prior to commencing treatment, means that in the future, we'll be able to determine the best treatment choice through retrospective meta analyses. (Remember, these prognostic indicators can change over time,).

Neil

[JustAGuy in reply to AussieNeil]

May I clarify this? If 7 years ago I had FISH and it showed that I am T12, normal TP53, you are saying it is still advisable before treatment to repeat a FISH test?

[AussieNeil Administrator in reply to JustAGuy]

Yes, with the exception of IGHV mutation status, which is unlikely (but not impossible to change), markers can change over time. That's why in countries with universal health care systems, prognostic marker testing is done just prior to treatment. You get clonal evolution over time, with sub-clones possibly developing. It's more likely when you have a complex karyotype (less genetically stable) CLL.

Neil

[SeymourB in reply to AussieNeil]

AussieNeil -

Ever since my IGHV status changed from Mutated to Unmutated, I've found more references to changes, as well as bi-clonality, and poly-clonality, plus allegations that it's more common than previously thought. Of course, I've had 11 years to develop knew clones. So I think time is a huge factor, too.

=seymour=

[patagozon in reply to AussieNeil]

Prior to starting treatment, I met with a CLL specialist to discuss my desire to be treated with O+V. At that point, I had never had my TP53 tested. He told me if my TP53 came back positive (mutated), he would advise against O+V and would recommend acalabrutinib instead. My TP53 test came back negative, so I went the O+V route. I was just wondering if it's a standard recommendation to avoid O+V if you are TP53 positive?

[AussieNeil Administrator in reply to patagozon]

I'm glad you met with a CLL specialist to help you with your treatment decision. I wouldn't say it's a standard recommendation to avoid O+V if you are positive for TP53 mutated or deleted, but it seems that it does give you the best chance of a normal life expectancy.

Neil

[mickimauser11]

there will be a new study by Dr Jain rtobrutinib Obinutuzumab and Venetoclax 3threefold treatment f e A OV or IOV is also used for complex karyotype at least in different trials

[bkoffman CLL CURE Hero]

CLL Society pioneered Test Before Treat (cllsociety.org/newly-diagno... and sadly it is still needed as too much chemo is given today without proper testing. As others have stated, TP53 and iFISH can change, so they need to be recheck before each treatment. One might argue, if you are going on a target therapy no matter what, why bother but I think knowing your low vs high risk status might suggest the use of one versus two orthogonal therapies. Also it can help you monitor the evolution of the CLL over the years to aid with planning. Knowledge is power. Stay strong

[UKwoman]

I was told at my hospital appointment two weeks ago that I will need to start treatment shortly and that the alternatives here in the UK are O + V or acalabrutinib. However he also took bloods for cytogenetic testing to see if one treatment would be preferable to the other. Reading the above replies, I am very happy that this has happened as it gives me confidence that my specialist knows what he is doing!

[Sanders9 in reply to UKwoman]

Hi is your consultant a CLL specialist? If not then I recommend you speak to one. My husband is moving towards his second treatment and a long list of options have been discussed with him.