W&W before treatment vs after initial treatment

[MikeOr]

A standard practice for treatment naive CLL patients is initial Watch & Wait, until WBC becomes high or clinical symptoms become obvious. Could the same W&W strategy be used after initial treatment with BTK inhibitors (after it has been interrupted b/o side effects with CLL in partial remission), or the treatment better be restarted right after CLL starts to return ?

[SofiaDeo]

I am not sure there are any definitive studies out yet to answer this. I know there is a study started to see if W&W is better than early specific treatment, but I am unaware of even preliminary results. I am not sure what you mean by "partial remission" so can't address that. You haven't mentioned the side effects, so it's difficult to say "yes restarting would be safe to attempt" or not, let alone if restarting the same med is desirable. There is some discussion going on of "is it possible/desirable to put in a patient in uMRD, continue the med awhile to make sure the CLL is really tamped down, stop treatment, then re-start the same treatment later if/when the disease resurfaces". As well as "if we choose to do this, how long do we keep patients on the drug in uMRD before pausing/stopping". ""What is best if resistance starts to emerge." People are asking, but I don't think there are studies out giving definitive answers yet.

[AussieNeil Administrator]

Further to the reply by SofiaDeo , maintenance therapy is a new development for CLL, plus we have only been trialling time limited combination targeted therapies for several years. It will be a few years yet before we know:-

1) How to decide who should best have time limited vs maintenance therapy with the new (and growing! ) targeted therapy options

2) Whether a subset of patients are best transitioned to what should be a long lasting remission by adding another drug class, typically a BCL-2 drug such as venetoclax/Venclexta, or if they reach uMRD on their BTKi maintenance therapy

It seems some of us may be able to look forwards to long remissions after coming off long term BTKi maintenance therapy, whereas others can see their CLL quickly rebound. We are just seeing some early ibrutinib trial participants achieve 10 years of control of their CLL. We also now know that only about 10% reach uMRD after 4 years on ibrutinib. BTKi class drugs work effectively at inhibiting CLL, so it stops growing, but apoptosis only slowly occurs, which is why it can take many years to get to uMRD, if ever.

Neil

[Big_Dee]

Hello MikeOr

Good question, not sure I have an answer. I am on my second round of W&W after having B+R treatment. I had very aggressive CLL with only 14 months W&W before treatment signaled by rapidly dropping RBC counts and rapidly raising WBC. We do W&W unlike other tumor cancers because past studies have shown most CLL patients have less time in between required treatments. Since I had aggressive CLL, I have blood testing every three months even though I am now in 4th year of my first remission. If my remission was shorter than my 14 month W&W, I would be in real trouble. If and when I relapse, I will not start re-treatment until a triggering drop in hemoglobin and platelets occurs. Whether or not adverse effects stopped your use of BTK, not sure anyone knows if you should wait until adverse "B" symptoms occur or try to get a jump start to achieve uMRD while you are in partial remission. May require long discussion with your doctor. Blessings going forward.