What is the longest remission that I can hope for?

[Research123]

I am wondering if there is any guide as to how long remission after modern treatments might last? For example V and O - are there any stats as to people who've had this, percent had it come back after 3 years, 4 years etc? And then how long until the next treatment is required or likely? I know everyone is different and some can be lucky or unlucky but I'm trying to get an understanding of the landscape

[Skyshark]

The latest report from CLL14 trial of V+O. Over 60% have not started a 2nd line treatment at 76 months. The time from detection of progression to start of next treatment increases with time to detection.

medically.gene.com/global/e...

If (as seems common) NHS haven't tested your IgHV status the answer is "no one knows". Without TP53mut/del(17p) it could be a PFS of 72% at 72 months or a median of 66 months from start of treatment.

Slower progression tends to indicate mutated IgHV, faster progression and bulky disease suggests unmutated.

CLL14 is a trial for older patients, median 72 years old in V+O cohort, that were unfit for FCR/BR and eligible for a milder chemotherapy, Chlorambucil-Obinutuzumab. The median age of initial cohort would have been 78/79 years by now, median age of survivors will be lower.

CLL14 PFS by IgHV/TP53 status

[johnliston in reply to Skyshark]

Nice graph Skyshark. Got another one for BTK inhibitors? It would be nice to compare.

john

[Research123 in reply to Skyshark]

Thank you That was very helpful. You'd think mutated was bad but seems to be a good thing in CLL. Anyway it doesn't look a bad graph at all. My numbers keep increasing so I wouldn't be surprised if I need treatment some time soon, but looks like there's a good chance of buying a chunk of time, and maybe by the end of that its come back then there will be a cure.

[Lily_Pad_Master]

Any analogous data available at this point from the triplet combination inclusive of Acalabrutinib (AVO)? I'm roughly 60 months out from initial MRD-undetetecability and spent another roughly 18 months on Acalabrutinib and Venetoclax. I'm IgHV unmutated.

[Skyshark in reply to Lily_Pad_Master]

No. (In a word)

CLL14 is the only trial to have reported by each of the four IgHV/TP53 status pairs. All other trials persist in obscuring the results, eg present 2 separate charts one with TP53/17p v's without and the other IgHV mutated v's unmutated.

CLL14 For the genetic marker pairs shown in italics the chart line shown in bold is a reasonably close result.

Ven-Obi TP53del/mut: median 51.9 months (n=25). IgHV unmut + TP53del/mut median 49 months. (n=16) months. (Removes 20% that do better.)

Ven-Obi without TP53del/mut: represents no one at all. (n=184)

Ven-Obi IgHV unmut: median 64.8 months (n=121). IgHV unmut w/o TP53del/mut median 66.6 months (n=103). (Removes 20% that do worse.)

Ven-Obi without IgHV mut: median NR, 74% PFS at 72 months (n=76). IgHV mut without TP53del/mut 74% PFS (n=71). IgHV mut + TP53del/mut 75% PFS (n=5).

All other trials (except FLAIR and possibly other MRD guided studies) show a very similar divergence pattern.

The phase 2 trial NCT03580928 for AVO started in 2018 doesn't seem have any reports for longer than 35 months. Based on the good response rate a new phase three trial was started NCT03836261, AVO v's FCR/BR this has recruited 984 patients and ends in Jan 2027. As FCR/BR doesn't work, it has excluded those with detected del(17p) or TP53 mutation. US may approve quickly in 2027 while UK, Canada and Australia will usually lag a bit longer.

This exclusion of patients with del(17p) or TP53 mutation was common after the finding that FCR/BR didn't work for them as FCR/BR was the standard of care comparator. Thus FLAIR for V+I and SEQUOIA for Zanubrutinib only have results by IgHV un/mutated without del(17p) or TP53 mutation. Overall results from these trials represent "no one at all", if results are shown by IgHV state they are representative. These trials have added (small) additional arms with del(17p) or TP53 mutation. Other trials such as CLL14 for V+O, GLOW for V+I, ELEVATE TN for A+O and Acalabrutinib sidestepped the FCR/BR exclusion by selecting older patients that were unfit for FCR/BR and for whom the standard of care was Chlorambucil-Obinutuzumab.

This report for AVO is just over a year old for 35 months.

targetedonc.com/view/avo-tr...

This is older 2022 but was also for 35 months.

ashpublications.org/blood/a... clinicaloptions.com/CE-CME/...

[Lily_Pad_Master in reply to Skyshark]

Thank you Skyshark. As a participant in NCT03580928, anecdotal reports are very good. I, too, wish there was more official disclosure, and I take comfort in the knowledge that the results were strong enough for most subtypes that the Phase 3 trial has begun. Personally, I'm unmutated IvGH and MRD-undetectable at 70+ months post-MRD-undetectability at 10-4 power. I have apparently, however, succumed to the anticipated increased risk of acquiring other, unrelated, cancers, by getting the male family scourge of prostate cancer. It was caught early at Gleason 6 and removed.

[Tonybdog]

Someone posted this article on the CLL FB support group that I found helpful so kept it for reference as I had the same question.

healthtree.org/cll/communit...

[Newdawn Administrator in reply to Tonybdog]

Excellent article Tony. Certainly elicited some gulps for me however! 😳

Newdawn

[Research123 in reply to Newdawn]

To be honest Newdawn I was a bit taken aback by the length of your remission which I thought would have been a good chunk longer, hence this post. Still I think the treatments are getting drastically better so not sure when you'll need treatment again but If they don't have a cure by then, it won't be long - medicine has become a digital science meaning the improvement is exponential

[Tonybdog in reply to Newdawn]

I’m so sorry…there’s new treatments coming out all the time. We just have to stay positive and hope when the relapse comes that’s there are new treatments that will hopefully give us a permanent remission. Everyone is so different with CLL,..Stay positive!

[Skyshark in reply to Newdawn]

MURANO results may not apply to BTKi or Ven prior treatment.

There's a trial of PVR for R/R, it's still open.

[Skyshark in reply to Tonybdog]

As I posted earlier, a set of results that correspond to "no one at all" (TM).

The person with "No del(17p)/TP53 mutation" that has BOTH IgHV mutated AND IgHV unmutated doesn't exist.

"With del(17p)/TP53 mutation" result is bolstered by the inclusion of 20% with IgHV mutated, deduct 2 months for IgHV unmutated.

"Mutated IgHV", 7 years is the 84 month extent of data from CLL14 for both with/without del(17p)/TP53 mutation.

"Unmutated IgHV" result is reduced by the inclusion of 20% with del(17p)/TP53 mutation, add 2 months for no del(17p)/TP53mut.

No One At All (TM)