ASH 2023 Unveils A “New Gold Standard” for CLL TreatmentUpdated Jan 17, 2024ByRuth FeinMedical ReviewerKerry A. Rogers, MD

[bagelstreet225]

I came across this amazing article. CLL/SLL is moving closer to a functional cure. I think it's practice-changing.

patientpower.info/chronic-l...

Best,

Pat

[Jm954 Administrator]

This is excellent news isn't it! Even more so because Ib+Ven is available as a first line treatment for all treatment naive CLL patients in England and Wales (depending on their fitness to tolerate it).

I posted about this back in January and there's a bit more detail here.

healthunlocked.com/cllsuppo...

Jackie

[bagelstreet225 in reply to Jm954]

Yes, Jackie, it's great news!!!

[Skyshark]

I+V is slow to achieve uMRD4. For a large proportion FLAIR has become a 6 year maintenance therapy with the two drug combo. This will make it far too expensive for NICE to approve for UK NHS for the foreseeable future.

m-CLL the median and mean time on treatment is 4 years, 60% stopped V+I by 4 years. The 89% PFS at 48 months is worse than 94.5% for fixed duration 15 cycle 60 weeks V+I on CAPTIVATE FD and 91% for GLOW.

u-CLL the median time on treatment is 2 years and mean 3 years, 80% stopped by 4 years. The headline 95% PFS at 48 months is remarkable compared to 75% for CAPTIVATE FD but I observe that 55% were only 2 years from end of treatment, 20% 1 year EOT and about 25% still on treatment at 4 years. CAPTIVATE FD 1 year EOT PFS 97%, 2 years 86%. for the 55%/20%/25% split it works out to 92%, 95% doesn't seem so keen given the increase in duration of treatment. Both CAPTIVATE FD and GLOW have about 60% PFS at 54 months, median can be expected at about 6 - 6½ years, it remains to be seen just how durable MRD guided FLAIR is.

Build up of uMRD4 in FLAIR trial.

12 months 47.5%, 47.5% stop at 2 years.

24 months 70.5%, 23% stop at 4 years.

36 months 83.2%, 12.7% stop at 6 years.

48 months 89.2%, trial ends at 6 years but using trial rules indicates 6% stopping at 8 years.

60 months 92.7%, 3.5% stop at 10 years?

It nearly gets there but the cost is enormous. It will need to show for the 83% that stopped at 2, 3, 4, 5, 6 years that the PFS is maintained for 10 or 15 years from end of treatment to start claiming "cure". (FCR is 6 months not years.)

CLL14 V+O now says uMRD4 should be an objective but it's not clear how that can be achieved by all - the 22% that failed to reach uMRD4 being the ones that need to reach uMRD4. There was little change in numbers with uMRD4 from cycle 7 to cycle 12 and a small increase at 3 months after EOT to 78% can be attributed to them testing some subjects that were previously "missing".

GLOW trial V+I has found that although fewer reach uMRD4 it is retained by more for longer than for V+O.

globenewswire.com/news-rele...

Slide from.

vumedi.com/video/ash-2023-i...

Early uMRD is not sustained.

[MVH_Somerset in reply to Skyshark]

Thank you for providing all this information Skyshark. I must admit that I don’t understand a lot of the statistics, but it appears that you have a far greater understanding of these trial results than I do.

However, I do know that (as is mentioned in the post by Jm954), I+V has been approved by NICE for NHS use, and in January I was offered it as the treatment I will be starting later this year. So I’m perplexed by your statement that “This will make it far too expensive for NICE to approve for UK NHS for the foreseeable future.” Have I misunderstood something here?

[Skyshark in reply to MVH_Somerset]

I+V as approved by NICE for routine NHS use is a 15 cycle 60 weeks Fixed Duration treatment. This is the protocol used by GLOW and CAPTIVATE trials.

The open ended MRD directed protocol used by FLAIR trial is completely different and very costly. For mCLL it is 4x more expensive and for uCLL it is 3x than the 15 cycle treatment.

[MVH_Somerset in reply to Skyshark]

Thank you for the explanation.

[Jm954 Administrator in reply to MVH_Somerset]

Irrespective of cost, this treatment is approved by the NHS for any patient that their doctor feels would benefit. It won't be suitable for everyone but for fitter patients with adverse markers it offers the best chance of a durable long term remission.

[LeoPa]

But the cost... There's no way public health insurance can cover it for all the patients that would need it.

[Phil4-13]

bagelstreet225, I LIKE this news. Everyday CLL research is getting better results. 🙂 Sandra

[bagelstreet225 in reply to Phil4-13]

Yes, Sandra, the treatment landscape has changed. Soon, we'll be talking about a functional cure, not a cure but we're on the way.

God Bless You,

Pat

[Phil4-13]

bagelstreet225, thank you. 🙂 Sandra

[AnnLacey]

I have been a CLL patient for 15 years and had 6 different treatments including ibrutinib and venetoclax (not together). I failed on both of them - had to stop due to side effects. So I won't be offered this. But I am interested in the revolutionary thought that doctors might tailor treatment to each patient. I got my longest remission so far from intensive obinituzemab! This was far less toxic than the others.