Importance of CLL Specialist

[PennyLane2024]

This excellent study was just published. Why should you get a CLL specialist? My community oncologist gave me a fish and a flow test and told me that I wouldn’t need treatment for 3-5 years. He didn’t test for IGVH and didn’t know that there is a specific TP53 test. My CLL specialist tested for 500 mutations. I started treatment due to rapidly growing lymphocytes before I received my test results. It turned out that I was unmutated, notch 1, SF3B1 which usually means rapid growth. If these tests had been taken months earlier, then I could have been monitored more closely which would have saved me a hefty hospitalization bill. If you have 17, 11, or 12 on your Fish test and unmutated on your IGVH test, then find a CLL specialist who can get you tested for the other mutations mentioned in this article.

frontiersin.org/journals/on...

[AussieNeil Partner Administrator]

This is an excellent article, providing a comprehensive overview of commonly used CLL prognostic markers and those that are likely to become used in the future. I've linked to your post from our introductory post for new members: healthunlocked.com/cllsuppo...

Thanks!

Neil

[spi3]

Ty for sharing this important information

[bennevisplace]

Good find, thanks for posting.

[lexie]

Great article! Thanks!

To your title, never under estimate the value of having a good CLL specialist for seemingly unrelated issues, as well. For example, my CLL specialist was able to get Evusheld early in the pandemic, as soon as we read of it. The esteemed Cleveland Clinic couldn't get it until much later in the year.

[SeymourB]

PennyLane2024 -

There are so many additional prognostic indications not covered in the article, and it's hard to know whether they combine to be worse or not.

The real question that the paper does not address is whether it's better to start treatment sooner if there are higher risk markers. I haven't seen any guidelines that say so. My instinct is that it's an arithmetic problem based on current age and life expectancy, which none of us really looks at closely, either.

Current guidelines only focus on del17p and TP53, because such patients get longer remissions BTKi monotherapy or BTKi combos.

So we get the relative prognostic doom to set our expections, but there's not much we can do about it. Yet.

=seymour=

[PennyLane2024 in reply to SeymourB]

I know three people in their 50s who had some of these mutations who were admitted to the ICU due to life threatening complications caused by their CLL. They all started treatment in the ICU. All three of them could have avoided the ICU if they were being tested more frequently than every 3 or 6 months by a CLL Specialist. If you have several of these mutations AND symptoms that indicate that you will most likely need treatment, then monthly blood work seems like a smart idea.

With all of the excellent new treatments, starting treatment a year too early is much better than starting treatment a few months too late.

[SeymourB in reply to PennyLane2024]

PennyLane2024 -

I agree! I just think we need an update to the now 6-year old iwCLL Guidelines for indications for treatment. We need more analysis of earlier treatment. The only thing we can quote right now is the old ibrutinib study which concluded there is no advantage to early treatment. But it has been criticized on several counts.

ashpublications.org/blood/a...

CLL12: a positive answer to a poorly phrased question

Blood (2022) 139 (2): 151–152.

"Inexplicably the disease progression rate in the placebo group was much lower than predicted by the index (predicted median EFS of 24 months), clearly indicating that we need better and more robustly externally validated predictive indices to identify appropriate patients for any future early intervention trials.[6]"

"With a median follow-up of 31 months, no meaningful data are currently available on OS, the ultimate measure of patient benefit."

I would add that they did not assess Quality of Life, either.

The predictive index used by CLL12 ultimately became the CLL-IPI (International Prognostic Index), which has itself been questioned because of less predictive survival on targeted drugs.

ashpublications.org/blood/a...

Time for a new prognostic score in CLL?

Blood (2024) 143 (25): 2561–2562.

"Nevertheless, the authors were able to conclude that CLL-IPI retained prognostic value for progression-free survival (PFS), but with diminished discriminatory impact for the prediction of overall survival (OS)."

"The study describing the CLL-IPI was published in 2016, and the 5 factors were TP53 status (no abnormalities vs TP53 mutation or deletion or both), IGHV mutational status (mutated vs unmutated), serum β2-microglobulin concentration (≤3.5 mg/L vs >3.5 mg/L), clinical stage (Binet A or Rai 0 vs Binet B-C or Rai I-IV), and age (≤65 years vs >65 years)."

I conclude that the choice of markers determines the relative success of treatment, and that there's no simple answer. I think we should approach the question in terms of identifying the markers of people likely to benefit from earlier treatment, rather than fitting a standard to everyone.

=seymour=