ASH 2019: U-MRD kinetics in the CLL14 trial (V+O vs Chl+O)

[avzuclav]

In this trial, treatments were given for 12 months. Note the decreasing slope of the MRD levels until Cycle 12 (end of treatment), then the positive slope of MRD levels up to 24 months after treatment. Also note the depth of response with V+O compared to Chl+O, but similar slope profiles (MRD increases when treatment stops).

The horizontal red line is U-MRD4

(<1 cell in 10,000). The lowest level is U-MRD6 (<1 cell in 1,000,000). (Sometimes we see these as percentages, where U-MRD4 is 0.01% - here it is shown in absolute terms, 0.0001.)

My interpretation: Is 12 months of V+O enough?

Slide from the oral presentation: ash.confex.com/ash/2019/web...

[Mystic75]

Sometimes we see these as percentages, where U-MRD4 is 0.01% - here it is shown in absolute terms, 0.0001.

Thank you for pointing that out - didn't know that before!

[cllady01 Former Volunteer]

Thank you for your patient and thorough explanations regarding studies, avzuclav.

I am illiterate at graph reading.

[johnl]

I guess I'm a little disappointed in the way the CLL is coming back after treatment is stopped. Even after reaching very low UMRD at 12 mos the line is almost back to MRD positive at only 24 mos . It doesn't seem to me that would indicate the kind of treatment free remissions that patients who reached UMRD after FCR were getting. Better not throw that FCR in the trash just yet.

john

[Smakwater]

I agree with your interpretation.

I have also read that resistance to venetoclax increases when continued past 12 months. I am not sure how that should be interpreted yet.

JM

[PlanetaryKim]

Very interesting. Thanks for posting.

[Justasheet1]

Avz,

12 months is probably not enough but it’s hopefully short enough to avoid resistance and can you can be rechallenged again with Venetoclax.

Jeff

[avzuclav]

ASCO 2020 update for CLL14 MRD data.

18 months after end of treatment U-MRD4:

V+O = 47%

Clb+O = 7%

"Assessment of minimal residual disease 18 months after end of treatment showed that 47.2% of patients in the VenG arm had undetectable (u) uMRD ( < 10−4), 13% had low (L)-MRD (≥ 10−4 and < 10−2) and 7.9% high (H)-MRD (≥ 10−2), compared to 7.4% uMRD, 17.1% L-MRD, 26.9% H-MRD in the ClbG arm. "

meetinglibrary.asco.org/rec...

[avzuclav]

EHA 2020 update with images:

library.ehaweb.org/eha/2020...

[avzuclav]

A few images from the Sept. 1, 2020 Lancet article are posted in this tweet. The last image shows the U-MRD kinetics for both arms.

twitter.com/tobyeyre82/stat...