Another BTK Inhibitor for Certain Leukemias and Lymphomas 

The FDA has approved pirtobrutinib for patients with heavily pretreated chronic lymphocytic leukemia or small lymphocytic lymphoma. 

The U.S. Food and Drug Administration (FDA) has granted accelerated approval to pirtobrutinib (Jaypirca) for the treatment of adults with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) after at least two prior lines of therapy, including a Bruton’s tyrosine kinase (BTK) inhibitor and a BCL-2 inhibitor. 

Blood smear of chronic lymphocytic leukemia where effected areas are highlighted in purple.

Pirtobrutinib is a type of targeted therapy called a tyrosine kinase inhibitor. It blocks the activity of BTK, which is commonly expressed on the B cells that make up certain leukemias and lymphomas. Because pirtobrutinib binds to BTK in a different way than other BTK inhibitors, it can sometimes benefit patients whose cancers have become resistant to other BTK inhibitors. 

This is the second FDA approval for pirtobrutinib. It was previously issued an accelerated approval in January 2023 to treat patients with mantle cell lymphoma that had progressed after treatment with another BTK inhibitor.  

The current approval was based on data from the open-label, international, single-arm, multicohort, phase II BRUIN trial. Researchers recruited 108 patients with CLL or SLL that had been previously treated with at least two prior lines of therapy, including a BTK inhibitor and a BCL-2 inhibitor; 77% of patients had discontinued their previous BTK inhibitor due to disease progression or lack of treatment response. 

All patients received pirtobrutinib until disease progression or unacceptable toxicity. The overall response rate was 72% (all partial responses), and the median duration of response was 12.2 months. 

CLL and SLL are two cancers that occur when a patient has too many immune cells called B cells; if most of the abnormal cells are found in the blood and bone marrow, the disease is considered CLL, and if most of the abnormal cells are found in the lymph nodes and spleen, the disease is considered SLL. According to federal statistics, it was estimated that 18,740 individuals would be diagnosed with CLL and 4,490 patients would die of the disease in the United States in 2023. 

The FDA rendered its decision on December 1, 2023. Accelerated approval means that continued approval may be contingent upon a confirmatory trial.