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The New England Journal of MedicinePirtobrutinib after a Covalent BTK Inhibitor in Chronic Lymphocytic Leukemia

The trial involved 317 patients with CLL or SLL, including 247 who previously received BTK inhibitor treatment.


The recently concluded phase 1-2 trial of pirtobrutinib, a highly selective, noncovalent BTK inhibitor, offers promising new hope for patients with relapsed or refractory B-cell cancers such as chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) previously treated with covalent BTK inhibitors.

Key Points:

  • Median number of prior therapy lines for these 247 patients was three.
  • Overall response rate to pirtobrutinib was 73.3% and increased to 82.2% when including partial responses with lymphocytosis.
  • Median progression-free survival was 19.6 months.

Additional Points:

  • Among the 247 patients, 40.5% had received a BCL2 inhibitor such as venetoclax.
  • The most common adverse events among all patients were infections (71.0%), bleeding (42.6%), and neutropenia (32.5%).
  • Adverse events typical of BTK inhibitors, including hypertension, atrial fibrillation, and major hemorrhage, were infrequent, and only 2.8% of patients discontinued pirtobrutinib due to treatment-related adverse events.

Conclusion:

  • Pirtobrutinib demonstrated efficacy in heavily pretreated CLL or SLL patients who had received a covalent BTK inhibitor, with a manageable side-effect profile.

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Did You Know?
As of 2021, chronic lymphocytic leukemia (CLL) is the most common type of leukemia in adults, accounting for about one-third of all leukemia cases in the United States.

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