2025 Update about Chronic Lymphocytic Leukemia, its epidemiology, pathogenesis, diagnosis and therapy

[CLLerinOz]

The American Journal of Hematology has published German CLL specialist Michael Hallek's 2025 update about CLL, its epidemiology, pathogenesis, diagnosis and therapy.

"ABSTRACT

Disease Overview

Chronic lymphocytic leukemia (CLL) is the most frequent type of leukemia. It typically occurs in older patients and has a highly variable clinical course. Leukemic transformation is initiated by specific genomic alterations that interfere with the regulation of proliferation and apoptosis in clonal B-cells.

Diagnosis

The diagnosis is established by blood counts, blood smears, and immunophenotyping of circulating B-lymphocytes, which identify a clonal B-cell population carrying the CD5 antigen as well as typical B-cell markers.

Prognosis and Staging

Two clinical staging systems, Rai and Binet, provide prognostic information by using the results of physical examination and blood counts. Various biological and genetic markers provide additional prognostic information. Deletions of the short arm of chromosome 17 (del(17p)) and/or mutations of the TP53 gene predict a shorter time to progression with most targeted therapies. The CLL international prognostic index (CLL-IPI) integrates genetic, biological, and clinical variables to identify distinct risk groups of patients with CLL. The CLL-IPI retains its significance in the era of targeted agents, but the overall prognosis of CLL patients with high-risk stages has improved.

Therapy

Only patients with active or symptomatic disease or with advanced Binet or Rai stages require therapy. When treatment is indicated, several therapeutic options exist: combinations of the BCL2 inhibitor venetoclax with obinutuzumab, or venetoclax with ibrutinib, or monotherapy with one of the inhibitors of Bruton tyrosine kinase (BTK). At relapse, the initial treatment may be repeated if the treatment-free interval exceeds 3 years. If the leukemia relapses earlier, therapy should be changed using an alternative regimen.

Future Challenges

Combinations of targeted agents now provide efficient therapies with a fixed duration that generate deep and durable remissions. These fixed-duration therapies have gained territory in the management of CLL, as they are cost-effective, avoid the emergence of resistance, and offer treatment free time to the patient. The cure rate of these novel combination regimens is unknown. Moreover, the optimal sequencing of targeted therapies remains to be determined. A medical challenge is to treat patients who are double-refractory to both BTK and BCL2 inhibitors. These patients need to be treated within experimental protocols using novel drugs."

The full paper is a very thorough reference for those wanting to get a better understanding of what is currently understood about chronic lymphocytic leukemia and its treatment.

Hallek, M. (2025), Chronic Lymphocytic Leukemia: 2025 Update on the Epidemiology, Pathogenesis, Diagnosis, and Therapy. Am J Hematol, 100: 450-480. doi.org/10.1002/ajh.27546

Note: this is an unlocked post so anyone, even those outside our community, can read it. If you want to ask a question related to your own situation, it's advisable to start your own locked post. There's more information about locked and unlocked posts here: healthunlocked.com/cllsuppo....

CLLerinOz

[bennevisplace]

Thanks for this, a comprehensive review by one of the leading lights in CLL research. At good year's worth of reading in the papers referenced.

[Fran57]

Thank you. I will read this asap…. It’s my husband who has CLL… but I try to keep up to date with all the relevant news and information.

P.S. I’m having eye surgery this week ( vitrectomy for full thickness macular hole) … so, if I can be cheeky, and ask, does anyone here (we’re in the UK)have experience of this??

Thanks again,

Fran 🥰

[CLLerinOz Administrator in reply to Fran57]

Hello Fran

You may get more of a response from one of our HU communities that's more relevant to your inquiry.

There's a HU community associated with the UK's Macular Society and it has a number of posts about surgery for a macular hole.

healthunlocked.com/maculars...

macularsociety.org/

All the best for your procedure.

CLLerinOz

[Fran57 in reply to CLLerinOz]

Many thanks for that😉

[SeymourB]

CLLerinOz -

On February 7, 2025, the NCCN (National Comprehensive Cancer Network) in the U.S. issued it's version 2 update for 2025.

Based on results from the AMPLIFY trial presented at ASH 2024, they added a recommendation for Venetoclax + acalabrutinib ± obinutuzumab (AV or AVO) as a preferred regimen for first line CLL. AV/AVO is not yet FDA approvedd.

When they added a similar recommendation for Zanubrutinib a couple of years ago, FDA approval was soon granted. Rumors are that we can expect AV and AVO approval this year.

Their endorsement of AV/AVO may allow patients to get insurance coverage for these treatments based on a physicial appeal letter. Several patienst have reported on Facebook of getting insurance coverage for AV/AVO.

This is important for del17p, mutated TP53, or complex karyotype where specialists might prefer fixed duration AV or AVO over the existing recommendation for IV or AO for a deeper remission, and for a therapy that can be repeated or extended if deep remission is not achieved.

The NCCN Clinical Guidelines for CLL are the most comprehensive and well documented guidelines for CLL, with over 300 references, and easy to read flow charts for physicians. They are updated several times a year, and are constantly reviewed. Patients can download them as well after creating an NCCN account.

nccn.org/professionals/phys...

=seymour=