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Treatment Tradeoffs. Very good Video. Debate: Is it appropriate to treat patients with CLL earlier in the era of novel agents? Dr. Furman

Treatment Tradeoffs. Very good Video.  Debate: Is it appropriate to treat patients with CLL earlier in the era of novel agents? Dr. Furman

Published on Apr 23, 2017

In this presentation from the 2017 Great Debates & Updates in Hematologic Malignancies, Dr. Richard R. Furman argues that, in the era of novel agents, it is not appropriate to treat CLL patients earlier than before.

FCR vs. Ibruvica Side effects

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That's what the new iwCLL Guidelines will state... no changes to firstline, TTFT.

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Thank you for posting this. I am 13q del and Ighv, and I think I fall into the VH4-39 area he speaks of regarding resistance or richters. (At least that is my reading of my profile.) I plan to ask Dr. Flinn about that.

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I think it is ... VH4-39, stereotype... usually Trisomy 12

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It is VH4-39---

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Chris: What doe he mean by XLA ?

john

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It is X-linked agammaglobulinemia, XLA..a genetic mutation of BTK, the Imbruvica (ibrutinib) target, that prevents it from working very well on some patients...

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Any information how to test for X-linked agammaglobulinemia? thank you

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Hopefully with drug combos like imbruvica plus Venetoclax the disease can get pushed way down and then get off treatment before it mutates. RT can happen before that though or independent of it.

I am on an I plus V trial. I am 17P deleted and trisomy 12. Probably mutated. They can't tell.

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Excellent, thanks.

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He does not discuss the main reason for treating early which is to stop clonal evolution leading to complex karyotype in unmutated. This is the main reason why the early treatment with ibrutinib clinical trials have been started

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Treatment, any treatment, is the primary accelerator of clonal evolution... it doesn't stop it. Read the works by Catherine Wu.

Nature abhors a vacuum... remove 90% B cells and something will replace them..and those will be aggressive clones, untouched by treatment...

iwCLL guidelines revision will say no fundimental change to TTFT...

I think its become clear than single agents, aren't going to do it, and combinations need to be trialed... hopeful to allow treatment cycling, for quality of life reasons and ongoing costs.

~chris

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Catherine Wu's paper from Octoer 2015: Clonal evolution is highly frequent in CLL patients before treatment, and in relapsed patients. It doesn't say that agents such ibrutinib accelerate clonal evolution. The German controlled trial is testing the hypothesis that early treatment with ibrutinib will prevent clonal evolution and lead to long term remission - and patients will be able to stop ibrutinib after several years without the need for long term treatment.

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Yeah..there is a new paper on clonal evolution, pre and post treatment, I think it was presented at ASH.

The CLL12 trial is looking at Imbruvica (ibrutinib) in firstline early treatment

Do you have a reference to the trial looking at cycling?

Early indications suggest Ventoclax and rituxan may be cyclable for those that get MRD negativity or perhaps a complete response. Need more mature data.

~chris

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My understanding is that all the clones are there at the very beginning and treatment treats some clones which allows the resistant ones to emerge and flourish. Fludarabine is a particularly nasty agent and from memory, although I can't reference it, can induce mutations and other clones (as well as AML later on).

I was very much in favour of treating earlier with the new agents but now I'm not so sure ...... I think the jury is still out on clonal evolution (apart from Richter's) with CLL.

Treatment naive patients on Ibrutinib seem to do extraordinarily well and, just my opinion, but I don't think anyone, apart from the younger Type 1, 13q:14, mutated patients with no other adverse markers and trisomy 12 patients, should get FCR.

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I agree

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I don't know how to quantity either but the way FCR works compared to targeted therapies seems like it can cause much more clonal evolution. The FC part that is. Secondary cancers with the FC part is another factor that is hard to quantify but is discussed in the video.

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Excellent talk. Thanks for posting. It is often hard to understand much of the scientific jargon but this dr made real sense.

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He is very good

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