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ASH 2021: Dr. Nitin Jain on First-Line Bruton Tyrosine Kinase Inhibitors for Chronic Lymphocytic Leukemia (CLL) with TP53 Mutations

In science and medicine, information is constantly changing and may become out-of-date as new data emerge. All articles and interviews are informational only, should never be considered medical advice, and should never be acted on without review with your health care team.

Checking for specific chromosome abnormalities and genetic variants can help doctors evaluate a patient’s prognosis and predict which patients will do well on or fail certain medications. For example, deletions of the short arm of chromosome 17 (del(17p)) are found in 5% to 8% of patients with chronic lymphocytic leukemia (CLL) or small lymphocytic leukemia (SLL) at the time of diagnosis. This includes the loss of the tumor suppressor gene TP53 that resides on the short arm (p) of the 17th chromosome. This used to be a dreaded diagnosis for patients with CLL/SLL since it is associated with resistance to chemoimmunotherapies and worse outcomes. However, targeted therapies such as Bruton tyrosine kinase (BTK) inhibitors provide new options for patients with del(17p) or TP53 mutations.

At the American Society of Hematology (ASH) 2021, Dr. Nicole Lamanna, Associate Clinical Professor of Medicine at Columbia University Medical Center, interviewed Dr. Nitin Jain, Associate Professor in the Department of Leukemia at The University of Texas MD Anderson Cancer Center. They discussed outcomes for patients with del(17p) or TP53 mutations who have been treated with first-line BTK inhibitors such as ibrutinib or acalabrutinib.

Takeaways:

  • Chronic lymphocytic leukemia with del(17p) or TP53 mutations is considered high risk, and we are still learning about the best way to treat patients with this type of disease.
  • This was a retrospective study (meaning that researchers looked back at the medical records of patients who had already been treated) to see what the outcomes were for patients with del(17p) or TP53 who received either a BTK inhibitor or a BTK inhibitor plus venetoclax for their first-line treatment.
  • A total of 140 patients were identified from the MD Anderson database. Patients were also assessed for the amount of mutation present in their cells.
  • The amount of del(17p) or TP53 mutation did not affect outcomes. In addition, all patients responded equally well to ibrutinib or acalabrutinib irrespective of whether they had a high or a low mutation level.
  • It also did not matter whether patients had either del(17p) or TP53 mutation or both. They did equally well.
  • This emphasizes the need to Test Before Treat with both FISH for del(17p) and with next-generation sequencing (NGS) for TP53 mutations.
  • Four years after starting treatment with a BTK inhibitor, progression-free survival was 73%, and overall survival was 87%.
  • There is no role for chemoimmunotherapy in these patients.
  • Progression-free survival was better in patients who received a BTK inhibitor plus venetoclax compared with patients who only received a BTK inhibitor.
  • Randomized controlled trials would be needed to confirm whether a BTK inhibitor + venetoclax is better than a BTK inhibitor alone for patients with del(17p) or TP53 mutations.
  • More data will come in the future from the SEQUOIA trial evaluating the BTK inhibitor zanubrutnib alone and in combination with venetoclax for patients with del(17p). See our previous coverage of this trial here and here.

Conclusions:

Targeted therapies have changed the game for patients with high-risk mutations such as del(17p) and TP53. Compared with chemoimmunotherapy, these patients are experiencing much better outcomes on targeted therapies, such as BTK inhibitors. However, it is critical that patients get tested for these mutations before starting treatment to know what treatments might be most effective. See our Test Before Treat™ section for more information.

Please enjoy this interview with Dr. Jain from the ASH meeting, held in December 2021 in Atlanta, GA, and virtually.

You can read the actual abstract here: Retrospective Single-Institution Analysis of Patients with Chronic Lymphocytic Leukemia with TP53 alterations Treated First-Line with Bruton’s Tyrosine Kinase Inhibitor-Based Therapy

Take care of yourself first.

Ann Liu, PhD