Chronic lymphocytic leukemia/B-cell prolymphocytic leukemia. A tutorial for physicians, useful for us too.

[Jm954]

From Feb 2019

An extensive overview of CLL, directed at educating PCPs or GPs covering all aspects of the disease, investigation and treatment.

cancertherapyadvisor.com/ho...

Jackie

[caven]

This is a fabulous summary of the contemporary knowledge-base for CLL diagnosis, and especially treatment, all combined into a single link. It is certainly worth making a note of this source document. It could serve as a primer both for those fairly knowledgeable about the disease as well as those newly diagnosed who seek to deep-dive into the topic.

Jackie, thank you so much for identifying the source and sharing it with us.

*perhaps the only item missing is the date by which this is an update ~ pretty important in the fast-paced development of tx in CLL*

Caven

[Jm954 Administrator in reply to caven]

It was posted in Feb 2019 but I think it's older than that. December 2015 is the most recent reference cited so probably about a year after that?

I just thought it was a good basic article

jackie

[Mystic75]

Hi Jackie,

Thank you for posting - very helpful!

I didn't see a reference to Venetoclax regarding treatment - maybe I overlooked it.

Just curious Did I miss it? I looked at the article a couple of times but maybe I just wasn't seeing it.

D.

[Jm954 Administrator in reply to Mystic75]

It's written for general docs so the details of specialist treatment weren't too strong.

I also think that although it was published Feb 19 on the article I found, it's a few years older than that and venetoclax wasn't used as routinely as it is now.

Jackie

[Mystic75 in reply to Jm954]

Thanks Jackie!

[t2aa in reply to Mystic75]

It was copyrighted in 2014, so is dated already v

[Mystic75 in reply to t2aa]

Research is moving along so fast it doesn't take long for information to become dated. It really makes the forum that much more valuable and underscores the advantages of being treated by a CLL specialist.

[Jm954 Administrator in reply to t2aa]

If you check the references at the bottom some of them are more recent than that so original may have been 2014 but it has been updated

Jackie

[cllady01 Former Volunteer]

Thank you Jackie. A very useful item to have bookmarked--I printed it out for family to read, should they be interested at some point.

[avzuclav]

Here's another good summary just published for ASCO 2019. ascopubs.org/doi/full/10.12...

[caven in reply to avzuclav]

Thanks avzuclav.

This is the most important & comprehensive update on the status of ALL the therapies currently available for CLL ("Tailored Treatment Strategies for Chronic Lymphocytic Leukemia in a Rapidly Changing Era"). And it <is> up-to-date having been published just a few weeks ago, in May 2019.

I read as much as I can, on a daily basis, about CLL updates and find this summary to be the most valuable of all the documents I've reviewed & archived over the past few years in outlining in objective fashion the array of CLL treatments, the efficacy, and a path forward to u-MRD. The flow diagram in Figure 1 that provides guidelines for tx-selection for the different patient populations is a true 'keeper' (older/younger, with/without high risk markers, etc.).

(ABSTRACT: The treatment landscape for chronic lymphocytic leukemia (CLL) is rapidly evolving, with multiple agents recently approved. They include a glycoengineered monoclonal antibody (obinutuzumab), B-cell receptor signaling inhibitors (ibrutinib, idelalisib, and duvelisib), and the BCL-2 inhibitor (venetoclax). These compounds are dramatically changing the natural course of the disease. Nonetheless, despite improved survival rates, particularly in higher-risk disease (older adults, patients with unmutated IGHV, del(11q), and del(17p)/TP53 mutated), there is still room for progress. Given the panoply of highly effective therapies commercially available, it is important to define a tailored treatment strategy for this heterogeneous condition that considers balance of treatment efficacy versus toxicity or tolerance. This article summarizes the most promising clinical advances by reviewing the data from recent clinical trials and discussing meaningful clinical endpoints, including the role of minimal residual disease assessment. The recent development of therapies targeting dysregulated pathways is revolutionary and may ultimately lead us to not only achieve prolonged remission durations but also envision the possibility of a functional cure for a larger population of patients.)

See: ascopubs.org/doi/abs/10.120....

For those wishing to archive in a reference manager like EndNote/RefWorks, the DOI is: 10.1200/EDBK_238735. American Society of Clinical Oncology Educational Book 39 (May 17, 2019) 487-498.

ASCO articles generally begin with an outline of the BIG-PICTURE IMPLICATIONS and so I will clip the main points from that research review here:

PRACTICAL APPLICATIONS

The number of novel targeted agents approved for use in CLL has grown considerably. A tailored treatment approach requires knowledge of the patients’ comorbidities, fitness, and prognostic markers. The appropriate selection of the regimen and length of therapy (lifelong vs. fixed duration dosing) relies heavily on these characteristics because advanced age and poor performance status confer the highest risk for increased toxicity and intolerance.

A select group of patients (young, fit, with mutated IGHV, without del(17p)/TP53 or del(11q)) benefit the most from a defined course of therapy with FCR. With new and more targeted and immune-directed therapies in development, chemotherapy may be appropriate only in limited cases.

Ibrutinib, the first-in-class approved B-cell receptor signaling inhibitor, has changed the treatment paradigm in both the frontline and relapsed settings. At present, data support continuous ibrutinib use in the absence of progression or toxicity. The role of the addition of a monoclonal antibody to ibrutinib is being explored.

Deep molecular responses have been observed with the BCL-2 inhibitor venetoclax. The achievement of uMRD on venetoclax correlates with prolonged remissions. Venetoclax is approved for relapsed disease, and it is undergoing evaluation in frontline settings.

Combination trials aimed at achieving undetectable minimal residual disease (uMRD) remissions to allow “treatment-free remissions” are ongoing. This strategy may prevent the emergence of resistance mechanisms, especially in high-risk disease where clonal evolution can occur even with novel agents (e.g., del(17p)).

Caven

[BluMts]

Thanks for all the useful links you continue to give us, Jm954. Much appreciated.

I suffered from Doctors who were not up to date on CLL/SLL. My wish is that others do not go through what I did. So, I have to say that this paper is seriously out of date as far as best clinical practise and current well reported and accepted research shows in advanced countries. I see that the information is dated as published Feb 2019 . That is confusing.

If I was a new CLLer – I’d find out from research papers published in the last couple of years what the best treatments are, what a CLL specialist recommends without consideration of cost and then find out if my state health can afford to offer it or if privately insured whether insurance will fund it. If you can’t get your choice of treatment, you’ll feel you did your best and not have regrets later. Many, many developed countries fund Ibrutinib as a free first treatment for all and there are sound reasons for this. The UK for cost reasons has limited who will get treatment on Ibrutinib but there are many people on this forum getting Ibrutinib as first treatment having joined a UK trial. FCR may be the correct drug for a new patient, but they should be informed about the other newer options before making their choice. Venetoclax and Acalabrutinib are two other new drugs. Venetoclax licensed in more countries than Acalabrutinib.

Thanks again Jm954, I follow your posts with gratitude and hope my comments are OK with you and I want you to know I realise you are more informed about CLL and medicine than I am. Your link did take me to an article that had a fabulous lot of useful information and I will continue to refer to it. But feel very strongly negative about organisations giving out of date treatment information as gospel truth as it can be very limiting for some of us.

[Jm954 Administrator in reply to BluMts]

Hi BluMts, I take your comments on board and I initally hesitated to post it because of the lack of information about recent treatment developments but I thought it was a good overview of the basics of CLL biology etc which might help some people.

I hope you feel that we keep you up to date with treatment developments on this site, we do try to.

It's good to realise that you are well informed enough to be able to find the gaps in a post like this.

Best wishes

jackie

[BluMts]

Yes, of course this site is a God send. I've learnt so much from marvelous posts here and felt close to all on the sometimes rocky path we are on. Miss Chris and the sweet Lola.