My doctor says Watch & Wait, but I think getting treatment now would be better.
Won’t my cancer spread to other parts of my body and make my condition worse if I wait?
-
CLL behaves differently than most other cancers and several major clinical trials have shown that early treatment is potentially more harmful than waiting until symptoms reach a certain level. Since CLL is a cancer of the blood and lymph system it is already throughout your body so early treatment won’t change that.
-
Here is a video from late 2018 where Dr. Nicole Lamanna addresses this question:
All three guidelines are in agreement that patients with early-stage CLL should not be treated with chemotherapy until they become symptomatic or display evidence of rapid progression of disease.
+++++++++++++++++++++++++++++++++++++++
Rick Furman Jul 4 #30005
Wendy,
It does sound like treatment is indicated at this time. One thing to keep in mind, is that watch and wait is meant to differentiate those who are not going to need treatment for a long time from those who will need it shortly. Once CLL is active, there is no benefit to delaying therapy. Along those lines, watch and wait was a strategy developed when we only had chlorambucil and prednisone. Ineffective therapy with an impact upon bone marrow function. Now that we have all of these new agents, the downsides to starting therapy, in terms of marrow damage, are not there.
Rick Furman
+
Re: Significant Fatigue Triggering Treatment
From: Rick Furman
Date: Sun, 05 Jul 2020 16:42:28 EDT
Active is defined by the traditional measures:
1.Hemoglobin < 11
2.Platelets < 100,000
3.Symptomatic LAD or splenomegaly
4.B symptoms
5.ALC doubling in less than six months
There seems to sometimes be an interest in deferring therapy for as long as possible. In truth, once the disease is active, there is no benefit for delaying. This translate to meaning, there is no advantage not starting treatment with a hemoglobin of 10 g/dl, even if you are feeling fine.
There won't be any refinements in iwCLL or NCI guidelines for sometime given the need to generate data to impact those guidelines. There are several protocols testing early initiation of treatment (including on at Cornell with acalabrutinib) for various populations.
My approach is that with ibrutinib, we know 80% of the population will do exceeding well with single agent ibrutinib. Some high risk features (deletion 17p) predicts for patients doing less well with ibrutinib. Our belief is that earlier treatment might help prevent the development of the aggressive cells that lead to the aggressive behavior.
Rick Furman
+++++++++++++++++++
An opinion from Dr. Richard Furman Wed, 05 Sep 2018
"Nothing has changed as of yet for watch and wait patients. My belief is that for 75% of patients, watching and waiting, and then starting BTK inhibitor therapy will be sufficient to provide extremely long-term disease control of their CLL. For the other 25%, we have issues with transformation and BTK inhibitor resistance. These patients do need something different. One theory of mine is that earlier initiation of treatment might be beneficial. We are currently writing a trial to test this, but for now, we are still doing it the way we always have."
+++++++++++++++++
Mayo Clinic has started a clinical trial to test early treatment with Acalabrutinib:
ClinicalTrials.gov Identifier: NCT03516617 Recruitment Status : Recruiting
First Posted : May 4, 2018
Last Update Posted : September 27, 2018
This phase II trials studies how well acalabrutinib with or without obinutuzumab works in treating participants with early-stage chronic lymphocytic leukemia or small lymphocytic lymphoma at high risk of progression. Recruitment will be 120 patients at Mayo Clinic (in Rochester, MN, Scottsdale, AZ, and Jacksonville, FL).
-
Very specific exclusion criteria which include:
Date of CLL/SLL diagnosis ≥ 24 months prior to registration
Prior exposure to ibrutinib or to a BCR inhibitor (eg Btk or PI3 kinase or Syk inhibitors) or a BCL-2 inhibitor (eg venetoclax)
Known central nervous system (CNS) lymphoma or leukemia
-
The Inclusion requirements are:
Patients with any of the following indications for therapy:
Evidence of progressive marrow failure as manifested by the development of or worsening anemia (≤ 11 g/dL) and/or thrombocytopenia (≤ 100 x 10^9/L) not due to autoimmune disease
Symptomatic or progressive lymphadenopathy, splenomegaly or hepatomegaly
One or more of the following disease-related symptoms:
Weight loss ≥ 10% within the previous 6 months
Extreme fatigue attributed to CLL
Fevers ≥ 100.4 degree Fahrenheit (F) for 2 weeks without evidence of infection
Drenching night sweats without evidence of infection
(Outside the USA, IgHV mutation status doesn't influence treatment choice. I hope eventually it will, given those with unmutated IgHV are unlikely to have long remissions on BR or FCR. In my opinion, unmutated IgHV folk should not have chemoimmunotherapy!)
Update on the management of relapsed/refractory CLL
FCR treatment experiences (still gold standard CLL treatment in many countries, offering ~55% chance of a very long remission, (20+ years), if IGHV mutated, under 65yo)
Includes reply referencing 19 year long term study report into a "functional cure" shows combination targeted therapies prove slightly better so far - without AML/MDS risk.
Sec 1, Introduction and Disease Overview, frequency of chromosomal abnormalities, how they affect prognosis, why and how these subclones can change over time.
Standardised guidance for investigation and management of CLL in Australia and New Zealand
Do I have to drink eight glasses of water per day?
Yes, particularly initially, when it's very important to flush away toxins from rapidly dying CLL cells. All fluid intake counts, incl. foodshealthunlocked.com/cllsuppo...
Also, here's a link to information about the latest results from the GAIA/CLL13 study that compared Chemoimmunotherapy (fludarabine–cyclophosphamide–rituximab or bendamustine–rituximab) with 12 cycles of venetoclax–rituximab, venetoclax–obinutuzumab, or venetoclax–obinutuzumab–ibrutinib
The CLLSA meeting in London at Bart's again confirmed that W&W is the correct 'treatment' for early stage CLL and starting treatment early has not been shown to have any benefits.. If this was explained at diagnosis by the doctor it would save a lot of worry. Unfortunately most seem to be told we will see you again in 6 months or a year without any explanation.
Yes I totally agree. My frustration comes in when so many factors are added in and then my Dr. and many posts say, well how do you feel? Not so great I say but is it the CLL? And then so many times you never know how crappy you feel until you really feel better. Without a point of reference its a tough call. I'm not running for or to FCR, if it will buy me 10 years as studies say great BUT I can still W and W too. Thanks for your post
I have an analogy for this that women in particular can relate to. Prior to labor starting, women often experience Braxton-Hicks contractions. For a first time mom, these may be confused with the beginning of labor. However, rarely do women get them confused after going through labor.
People read about fatigue being a symptom of CLL but the fatigue when one needs treatment is in a class by itself. It feels like you are collapsing. You can think of it as sitting down in a chair and being absorbed by the chair.
Is It Time to Treat Your CLL? What You Need to Know. Dr. Susan O’Brien, reviews key decision-making factors, current CLL treatments and emerging research (August 2020)
Younger, Fit Patients With CLL: Goal Remains Undetectable Minimal Residual Disease and Time-Limited Therapy - Dr Jennifer Brown, Director, Chronic Lymphocytic Leukemia Center, Dana-Farber Cancer Institute, comments on the findings of the interim analysis of E1912, a U.S. Intergroup–led randomized phase III trial comparing ibrutinib/rituximab, followed by ibrutinib to disease progression vs 6 months of fludarabine, cyclophosphamide, and rituximab.
I highly recommend this Chronic Lymphocytic Leukaemia primer, by Thomas J. Kipps, Freda K. Stevenson, Catherine J. Wu, Carlo M. Croce, Graham Packham, William G. Wierda, Susan O’Brien, John Gribben, and Kanti Rai (Many of those names will be familiar to those that have had CLL for some time).
The Invention of CLL Bucket classification was created January 1, 2010 by Chaya Venkat. At that time CLL treatments were not as good as today. The statements made in the article may not apply in today's treatment strategies, but the Bucket classification lives on. (see link and photo). clltopics.org/PI/Type.html
A report and accompanying commentary on the CLL12 trial has been released this week.
The ‘phase 3, double-blind, placebo-controlled CLL12 trial randomly assigned asymptomatic, treatment-naïve Binet stage A CLL patients at increased risk of progression in a 1:1 ratio to receive ibrutinib (n = 182) or placebo (n = 181) at a dose of 420 mg daily.’
The report concludes that 'Ibrutinib is effective in patients with early-stage CLL, but the results do not justify changing the current standard of “watch and wait.”' (my emphasis)
The commentary by Prof John Seymour is titled 'CLL12: a positive answer to a poorly phrased question‘. It also concludes that the 'the results (of CLL12) do not justify any change to the current standard of “watch and wait.”' However, Prof Seymour suggests that 'well-designed early intervention trials should continue to be pursued.'
There's a separate post with more information and links to both the report and commentary at: healthunlocked.com/cllsuppo...
The British Society of Haematology published updated guidelines for the treatment of CLL in the UK on 21 March 2022 This post has more information and a link to a copy of the guideline document:
Content on HealthUnlocked does not replace the relationship between you and doctors or other healthcare professionals nor the advice you receive from them.
Never delay seeking advice or dialling emergency services because of something that you have read on HealthUnlocked.
ASH 2017: Dr. Richard Furman on the importance of MCL-1 in CLL (chronic lymphocytic leukemia)
Need a summary of treatment options
EHA 2022: Outcomes Following Treatment With a Covalent BTK and BCL2 Inhibitor
Ibrutinib, Acalabrutinib, or Zanubrutinib 
Watch and Wait Advice Needed please
