Determining if you'll never need treatment. It is feasible and safe to stop specialized follow-up of asymptomatic lower risk CLL?

[AussieNeil]

Regular readers will have often heard that around 30% of those diagnosed with CLL never need treatment. So how is it determined whether you fall into that category and if so, what's the best way to monitor whether your CLL/SLL becomes no longer asymptomatic?

For the former, we have the CLL-IPI, the Chronic lymphocytic leukemia international prognostic index: a systematic review and meta-analysis

The chronic lymphocytic leukemia international prognostic index (CLL-IPI), which combines 5 parameters (age, clinical stage, TP53 status [normal vs del(17p) and/or TP53 mutation], IGHV mutational status, and serum β2-microglobulin) to predict clinical outcome in chronic lymphocytic leukemia (CLL) patients was first published in 2016.1 The utility of this prognostic tool has been confirmed in independent validation studies across countries and in different practice settings (ie, academic medical centers, national population-based cohorts, and clinical trials).2-7

ashpublications.org/blood/a...

There's also CLL-WONT covered in this paper; Identifying patients with chronic lymphocytic leukemia without need of treatment: End of endless watch and wait?

onlinelibrary.wiley.com/doi...

So for those deemed to be at low risk, It is feasible and safe to stop specialized follow-up of asymptomatic lower risk chronic lymphocytic leukemia?

Key Points (from this Danish study)

ashpublications.org/bloodad...

* More than half of patients with low to intermediate risk CLL-IPI and CLL-WONT may safely end specialized follow-up

* Survival was similar and time to infection was longer in patients ending specialized follow-up compared to those who continued

That the" time to infection was longer" makes sense when you appreciate that even the precursor to CLL/SLL, Monoclonal B-cell Lymphocytosis (MBL) compromises your immune system. So visiting a hospital to see your specialist unfortunately does put you at increased risk of contracting an infection.

I've noted that some of our deemed low risk UK CLL members have their CLL monitored by their GP. Given CLL/SLL is deemed an orphan disease in the USA and Europe to encourage research and drug development, it's not something GPs/PCPs see all that often and even oncologists that don't see many CLL patients can struggle to keep up with the fast changing improvements in treatment options. An Australian Leukaemia Foundation survey determined that a GP would typically see about half a dozen lymphoma cases (CLL is the most common adult Non-Hodgkin's Lymphoma), in their entire career!

So if you are deemed to have low risk CLL/SLL, this is where your knowledge of CLL/SLL becomes very important in ensuring your long term health and why it makes sense to track your critical blood test results; haemoglobin and platelet counts and lymphocyte doubling time, as well as being observant about other changes in your body and health. You'll be able to advocate to obtain a referral to see a CLL specialist based on references from information posted here on the latest management and treatment guidelines.

We have plenty of excellent maintained pinned posts that will help you live long and well with a CLL/SLL diagnosis: healthunlocked.com/cllsuppo...

With respect to when treatment is deemed necessary, there are two main guideline documents in regular use, the USA's NCCN CLL guidelines (for which there are physician and patient versions) and the internationally used iwCLL guidelines, both of which are maintained by top level CLL/SLL specialists/researchers. The NCCN guidelines are more regularly updated; with the most recent updates in November 2023 and March 2024 for the patient and physician version 3.2024 guidelines respectively. The iwCLL guidelines document was last updated in 2018. The triggers for starting treatment are closely matched, with the NCCN guidelines more up to date with regard to including newer treatment options and providing guidance on which treatment is more suitable, based on test results also used for determining the CLL-IPI risk rating.

The NCCN guidelines state that "Indications for initiating treatment include severe fatigue, weight loss, night sweats, and fever without infection; threatened end-organ function; progressive bulky disease (enlarged spleen or lymph nodes); progressive anemia or thrombocytopenia; or steroid-refractory autoimmune cytopenia.

63 Absolute lymphocyte count alone is not an indication for treatment in the absence of leukostasis, which is rarely seen in patients with CLL."

The iwCLL guidelines includes the use of lymphocyte doubling time as an indication for starting treatment, which is not mentioned in the NCCN guidelines. "Progressive lymphocytosis with an increase of >=50% over a 2-month period, or lymphocyte doubling time (LDT) 30 x 10^9/L may require a longer observation period to determine the LDT. Factors contributing to lymphocytosis other than CLL (eg, infections, steroid administration) should be excluded."

See: When will I need treatment? Is Watch and Wait still the best option with newer treatments?

healthunlocked.com/cllsuppo...

The good news for those treated with targeted therapies, is that due to the improvement offered by these, there's a need for Reassessing the Chronic Lymphocytic Leukemia International Prognostic Index in the era of targeted therapies

ashpublications.org/blood/a...

Key Points

* The CLL-IPI retains prognostic value for PFS, but its impact appears diminished in predicting survival with targeted drugs.

* Improved survival with targeted therapies vs. chemoimmunotherapy underscores the need to reevaluate prognostic tools amid treatment shifts.

Note particularly the good news that; "Targeted therapies showed enhanced outcomes over chemoimmunotherapy, highlighting their effectiveness across various risk groups."

Neil

[ChristineAM]

Thank you !

[Rohail]

Thanks Neil for all the efforts you put in to keep CLL patients informed. Today I was watching the All in podcast which is one of my favorite channels on YouTube. I heard David Friedberg talk about AI aiding in gene editing and finding new cas proteins that may be able to target cancerous cells more accurately. The details were a bit above my head. I was wondering do you see potential for that helping new treatments for CLL and attacking cancerous b cells? Or is that more only for solid tumor cancers?

[AussieNeil Partner Founder Admin in reply to Rohail]

Leukaemias are much easier for research studies than solid tumours, because it's so much easier to sample how the blood tumour is responding to a trial drug. The challenge with CLL, is that there are many tumour growth drivers, compared to many other cancers. (The first targeted inhibitor therapy, imatinib, was approved for Chronic Myeloid Leukemia (CML), because over 90% of the time it's caused by one genetic driver.) However, I would think that repairing mutated or deleted TP53 or unmutated IGHV would be good targets for genetic repair for those with these CLL drivers.

Neil

[Shepherd777]

Great article. Loved the 2nd key point at the end. " Improved survival with targeted therapies vs. chemoimmunotherapy underscores the need to reevaluate prognostic tools amid treatment shifts."

[Shrink]

t

Thank you Neil

[Living_and_Learning]

As always, thank you for helping us be the best advocates for ourselves.

[ChristyAnne_UK]

Good stuff, as always, Neil. Thank you.

[CoachVera55]

Yes thank you Neil even though much is over my head too. I did come to that same conclusion when I decreased my monthly surveillance to every 3 months with my Local Oncologist & to semi annual/annual with my CLL Specialist. I still request any healthcare provider to put on a mask & many act like its such a foreign request but I don’t care how far they have to go to get one lol. If my Hairdresser can place me in a separate room & require any braider to wear one why would a Whole Hospital act weird about it🤣😂😆

I got sick 2X over the year I’ve been on BTKIs, its just that the first infection took 3 months for me to get antibiotics on my own while my team just watched me decline. The second time it happened was when we increased the dose but this time I called 4 doctors, 2 Oncologist, Primary & ENT. Prompt treatment worked the best for me & I will push for that each time.

All my doctors are so fascinated by my lab numbers but this bone pain is quite severe & no one seems the least bit concerned about that. Ortho & I believe that weight loss will help & I pray it does because I do not want to stop this treatment. Its working miracles even on just half dosage.

I will never give up but its been hard😢My new Rolling Walker

[Phil4-13 in reply to CoachVera55]

CoachVera55, GO GIRL!!!👍😊 Sandra

[MVH_Somerset]

Thank you Neil for such a comprehensive and useful summary.

[Astro617]

Thank you Neil! This is very helpful!

[Stamphappy]

Thank you, Neil, for all you do for all of us. You're simply awesome!!

[Peggy4]

Hi Neil. Reading this in my work break so only skimming. So is it saying that people with low level CLL in long term Watch and Wait need not have blood draws or be monitored? Admit that this frightens me a bit. I no longer travel for a face to face appointment with my consultant but admit that my 6 monthly blood tests with phone call and the availability of a specialist nurse make me feel much safer. Plus the few times I have needed advice (covid, chickenpox etc…) they’ve been a great help. My own GP is excellent but during Covid he said I was fine to work (front facing hospital ward) whereas my consultant immediately said no.

Will it be a choice? I feel a bit concerned. Knowing I’m monitored and can ask questions if necessary (not often) makes me feel secure. My knowledge of CLL is ever increasing but I still like to know I’m monitored by people who specialise in the field.

Peggy UK (worried)

[AussieNeil Partner Founder Admin in reply to Peggy4]

Peggy, the post's purpose was to alert everyone of this trend away from specialist oversight for low risk patients. Blood tests are low cost and regular blood testing should not be abandoned when we have a diagnosis of CLL/SLL or even the precursor MBL. What we need to assure for our best health, is that if we end up potentially losing the oversight of our specialist, then we need to insist on:

1) Having a knowledgeable review of scheduled blood counts

2) Regular physical examinations for signs of increasing nodal or spleen involvement, etc.

3) Prompt referral back to a CLL specialist should there be any sign that our blood cancer might be on the move.

So I totally agree that we need to maintain prompt access to those who specialise in our blood cancer. GPs/PCPs should be aware of their lack of expertise in CLL/SLL etc., and be prepared to support this specialist access. Blood testing is highly automated, but I gather it's fairly common practice for pathology labs to have a pathologist review key results that are out of their reference range and add a note drawing this to the attention of the ordering physician. I would strongly recommend that everyone keep a copy of their blood test results and look for such notes, or indeed any out of range results. Then if they can't reassure themselves that these are expected (e.g. a lymphocyte count outside the reference range is a given with this diagnosis), they should be supported in having these results explained to their satisfaction by someone with the appropriate medical training and experience.

Neil

[Skyshark in reply to AussieNeil]

One such UK NHS scheme being this :-

hmds.info/diagnostic-servic...

[Peggy4 in reply to AussieNeil]

Thanks Neil. I will remain under my specialist as long as I possibly can. My GP is lovely but admits that he has gained knowledge from me. Initially with the injections he said that I did not need pneumonia etc…. But as soon as I was referred I was told to get them straight away. In UK now it’s very hard to actually get to see a GP. Indeed they are referring so much to the pharmacies that I fear they will soon be unable to cope under the strain.

Worrying times.

[Edalv]

Thanks Neil for the article, but I don’t know if I would feel comfortable not seeing my specialist at least once a year. I am currently asymptomatic with low lymphocytes burden. But it is reassuring to check with my oncologist at least once a year. I usually schedule my regular physical six month later. So I get my blood checked every 6 months by one or the other.

[CycleWonder]

I have to say that I would be nervous with my current GP monitoring my CLL. The one I had when I was diagnosed - yes, I would be comfortable. Interestingly, the one who diagnosed me is a physician’s assistant but was always much more invested in my health than my current GP.

My current GP flipped out when she saw my latest blood test results. I believe my ALC at the time was around 90k. I explained I had just seen my CLL specialist and he was not concerned. Nothing I said was taken into account. She sent a message to my CLL specialist and he had me come in just to reassure me all was well.

So, if people early on in their CLL journey or those with low risk CLL are seeing their GPs for follow-up, while it may make sense to the bean counters, I foresee a lot of miscommunications and chaos developing.

Not every patient with CLL regularly reads HealthUnlocked/CLL. Should they? Of course.😊 But for those that don’t and for GPs who don’t keep up with new developments in CL, we may well see the uninformed leading the uninformed.

I also just had a GP decide my son (who is 32) has dementia. He presented with pain and sleep disturbances, a text book case for GERD for a person with Down Syndrome. She opted for dementia.

Both my son and I need to change GPs!

Patti