Abstract: Here, we review the current understanding of the underlying interplay between the malignant CLL cells and non‐malignant immune cells that may promote tumor survival and proliferation. In addition, we review the available evidence on how different treatment options for CLL including CIT regimens, small molecular inhibitors (i.e, BTK inhibitors, PI3K inhibitors, BCL‐2 inhibitors) and T‐cell therapies, affect the immune system and their clinical consequences. Finally, we propose that a dual therapeutic approach, acting directly against malignant B‐cells and restoring the immune function is clinically relevant and should be considered when developing future strategies to treat patients with CLL.
This is a review article with forward looking intent.
Restoration of the immune function as a complementary strategy to treat CLL J Exp Clin Cancer Res (Oct. 2021) 40:321
Thank you, Gardening-girl! Cannot wait to dig down into this abstract. It is very encouraging to see that it may be possible for treatments to have less of a negative impact on the immune system in the future.
Mystic75, don't get your hopes up too high. The paper is a review of current treatments and their effect on various components of the immune system. As far as I could tell there didn't seem to even be an outline for a strategy for maintaining or restoring immune function, although it seems like they kept pushing ibrutinib to the forefront.
To quote four fairly obvious statements from the Conclusions:
"Keeping in mind that not only eliminating malignant B-cells, but also restoring the immune function may have significant positive consequences in the clinical practice, especially in CLL, that immune dysfunction is the cause of most of the complications for this disease. Also, understanding the relevance of the other immune players in CLL and how different treatments affect them would have a direct impact in successfully managing the disease."
-First, because this will allow us to avoid therapies that negatively impact the immune function, such as some chemotherapies.
-Second, because it will reduce the number of adverse events related to the immune dysfunction, for example infections, autoimmunity and second malignancies.
-Third, because this will facilitate the design of combination strategies, not only to reach deeper durable responses but to attack the disease from different fronts, with higher chances of synergistic and long-term effects.
-And four, it will allow us to successfully use the new generation of therapeutic strategies, most importantly immunotherapies and cell therapies, in CLL, so far inefficacious due to the immune dysfunction in CLL patients.
I worked backwards to the original PubMed.gov abstract, to see if PubMed noted any similar articles; it did not.
As many of you know, I've been following the story of prescription pentoxifylline now for over 10 years (it was prescribed for me in Year One).
Increasingly, med articles are referring to it as an "immunomodulator" -- & it certainly has anti-inflammatory effects (being a production inhibitor of TNF-alpha/ tumor necrosis factor-alpha & IL-6/ interleukin-6) -- as well as having pro-apoptotic ("programmed natural cell death") effects in this specific blood disorder.
But, pentoxifylline went off patent in 1998 & the price now has dropped to 3 pills for one US dollar -- so further research concerning this specific blood disorder would have to be funded out of some department's "petty cash" fund rather than by a pharmaceutical company. healthunlocked.com/cllsuppo...
[Pentoxifylline also is anti-viral, anti-bacterial, & anti-fungal, so speculative articles during the COVID-19 era have appeared. It is a distant relative of both caffeine & sildenafil.]
Restoration of the immune function as a complementary strategy to treat Chronic Lymphocytic Leukemia effectively
But as detailed as it appears, I wonder if it lacks some depth in its short paragraph on BCL-2 inhibitors. I'm particularly interested in BCL-2 venetoclax, and the idea that immune function can recover from it, unlike BTKi's. They cite the article below, and it has more info:
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Distinct immune composition in lymph node and peripheral blood of CLL patients is reshaped during venetoclax treatment
Trabectedin Targets Leukemic Cells and Restores Immune Cell Function in Models of Chronic Lymphocytic Leukemia
BTK inhibitors for the treatment of CLL - the current state of play of 'brutinibs'
