NCCN guidelines for healthcare providers are the gold standard where CLL experts use best evidence to recommend best practices. Payors generally must cover the recommended therapies.
So, it can be practice-changing when they are updated, and they change at least annually and more often if needed. Recommended drugs or new drug combinations not yet FDA-approved for CLL / SLL should be paid for and, therefore, can be used before formal FDA approval.
The most recent update had multiple tweaks, clarifications, and significant new recommendations.
The big news is that the latest (February 2025) NCCN (National Comprehensive Cancer Network) Guidelines for Chronic Lymphocytic Leukemia / Small Lymphocytic Lymphoma (CLL / SLL) have added the combination of acalabrutinib (a second-generation BTK inhibitor) and venetoclax (a BCL-2 inhibitor) ± obinutuzumab to their preferred frontline therapy recommendations. This inclusion is based on the positive outcomes from the AMPLIFY Phase III trial.
AMPLIFY Trial Overview:
- Design: A randomized, open-label, phase III study evaluating fixed-duration regimens of acalabrutinib plus venetoclax, with or without obinutuzumab, compared to standard chemoimmunotherapy in treatment-naïve CLL patients.
- Results: At a median follow-up of 41 months, the combination of acalabrutinib and venetoclax, with or without obinutuzumab, significantly improved progression-free survival (PFS) compared to standard chemoimmunotherapy. Specifically, the regimen with obinutuzumab reduced the risk of disease progression or death by 58%.
These findings have led the NCCN to recommend acalabrutinib and venetoclax, with or without obinutuzumab, as a preferred frontline regimen for CLL / SLL. This regimen offers a time-limited treatment approach with substantial efficacy.
This combination is not yet FDA-approved but is expected to be soon.
Another change was the move of pirtobrutinib from “Useful in certain circumstances” to “Preferred regimen” when there was resistance or intolerance to a prior covalent BTKi-based regimen.
There were several other tweaks and changes to the recommendations.
The patient version of NCCN guidelines written in patient friendly language is available for free online if you want a deeper, more granular description of the latest recommended CLL / SLL management. Unlike the more detailed healthcare provider guidelines, there is no need to set up an account and sign in.
Listen to Dr. Koffman’s monologue below.
