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Deletions of the short arm of chromosome 17 (del(17p)) are found in 5% to 8% of patients with chronic lymphocytic leukemia (CLL), and most of the time this includes deletion of the tumor suppressor gene TP53. This is a dreaded diagnosis for patients with CLL since it is associated with resistance to chemoimmunotherapies and worse outcomes. However, targeted therapies are providing new options for patients with del(17p) and closing the gap in outcomes.
At the annual meeting of the American Society of Hematology (ASH) 2020, our own Brian Koffman interviewed Dr. Anthony Mato, Director of the CLL Program at Memorial Sloan Kettering Cancer Center in New York. They discussed new research evaluating the efficacy of ibrutinib as a first-line treatment for patients with CLL and del(17p).
- One of the major limitations of the landmark clinical trials testing novel targeted agents, such as ibrutinib, for first-line use is that they have excluded most or all patients with del(17p).
- Patients with del(17p) were likely excluded because the comparator group was chemoimmunotherapy, and it would not have been ethical to randomize patients with del(17p) to this arm since they are known to have poor outcomes with this type of treatment.
- However, this does leave us with a gap in knowledge, where novel agents have not been studied in a large number of patients with del(17p).
- Real-world data allows us to examine questions that can’t easily be asked in clinical trials.
- This study used information from a national database to identify patients that had been treated with ibrutinib as a first-line therapy and then categorized them based on whether or not they had del(17p).
- Approximately 1000 patients were included in the analysis, and about 1 in 4 had del(17p).
- Patients with del(17p) had worse outcomes. Overall survival was significantly shorter, and time-to-treatment discontinuation tended to be shorter as well.
- While patients with del(17p) do better on ibrutinib than on chemoimmunotherapy, their outcomes are still not as good as patients without del(17p).
Targeted therapies have closed the gap in outcomes for patients with del(17p), and these patients are doing much better than they were on chemoimmunotherapy. However, there is still room for improvement and more work to be done. Studies are needed to specifically examine the efficacy of targeted therapies in patients with del(17p). Because del(17p) makes CLL harder to treat, patients with del(17p) might be good candidates for clinical studies of combination therapies or new agents in development.
Please enjoy this interview with Dr. Mato from the virtual ASH meeting which was held December 2020.
You can read the actual abstract here: A Clinical Practice Comparison of Overall Survival, Time-to-Next-Treatment, and Time-to-Treatment-Discontinuation Among CLL/SLL Patients Receiving First-Line Ibrutinib with and without a Del(17p) Mutation
Take care of yourself first.
Ann Liu, PhD
Ann Liu is a medical writer who lives in southern California. In a former life as a scientist, she conducted research on diet and chronic diseases such as cancer and obesity. She enjoys learning new things about science and health, and she also loves beagles and trips to the beach.
Originally published in The CLL Society Tribune Q1 2021.