The Evolution of CLL Treatment

Tara Graff, DO, MS: In my practice and clinical practices all over [the United States], novel agents have completely changed the face of treatment and outcomes for our patients with CLL [chronic lymphocytic leukemia] to the point that chemotherapy-immunotherapy is hardly, if ever, used anymore. At times, immunotherapy, in terms of our anti-CD20 antibodies, aren’t even being used conventionally. That’s a big thing, especially in the time of COVID-19, where immunosuppression with vaccines and the risk of COVID-19 has been a concern, especially in our patients with CLL. But in mainstream, having these targeted agents, patients can take a pill, and in some cases, they can take a medication and have a fixed duration of therapy, knowing they’re going to be coming off in X number of months. That’s a big deal. It’s completely changed the treatment landscape for CLL in the last 18 months. It’s a whole new ballgame.

Molecular testing in any newly diagnosed patient with CLL is critical. We need to routinely be doing FISH [fluorescence in situ hybridization] testing for cytogenetics. We need to be looking at different genomic aberrations, specifically for deletion 17p, TP53 mutation, and the IGHV mutational status. Too often, especially in community oncology, these are left out. They’re necessary to know if your patient has higher-risk disease, because that will determine their time to first treatment and possibly what medications you select. Patients who have higher-risk disease don’t conventionally respond to chemotherapy-immunotherapy. We stated that this isn’t really being used, but it’s important. The NCCN [National Comprehensive Cancer Network] Guidelines use those different genomic aberrations to dictate and help guide treatment. It’s very important that there’s some standardization for these different cytogenetics and mutations that are being routinely done in all practices.

By checking those markers, I’m going to go back to focusing on 17p deletion and IGHV mutational status. We use a prognostic test called the CLL-IPI [International Prognostic Index for Chronic Lymphocytic Leukemia]. Conventionally, we always use the Rai and Binet staging systems, but now we take those 2 older staging systems and use them to calculate a risk score using the CLL-IPI looking at the different high-risk cytogenetics, age, and beta-2-microglobulin, and calculating how many points you have. It correlates to your overall risk, lets you know your overall survival, and also lets you predict when somebody might need treatment. Those are really important. It all starts with looking at those chromosomal abnormalities to help guide treatment, and then also fold over into the CLL-IPI. It’s crucial that we continue to educate people that we need to be checking for these genomic aberrations routinely on all patients newly diagnosed with CLL.

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