FDA Approves Pirtobrutinib For Treating Adults With Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma

Anthony Calabro, MA

On December 1, the FDA granted accelerated approval to pirtobrutinib for treating adults with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). The use is granted for adults with either CLL or SLL who have received at least two prior types of therapy, including a Bruton tyrosine kinase (BTK) inhibitor and a B-cell lymphoma 2 (BCL-2) inhibitor. The FDA previously approved pirtobrutinib for treating those with advanced mantle cell lymphoma in late January of 2023.

The approval was based on the results of the open-label, international, single-arm, multicohort phase 1 and 2 trial, which included 108 patients with CLL or SLL who were previously treated with at least two prior lines of therapy, including a BTK inhibitor and a BCL-2 inhibitor. The main efficacy outcome measures were overall response rate (ORR) and duration of response (DOR).

In the trial, patients received a median of five prior lines of therapy (range: 2 to 11). Researchers administered pirtobrutinib 200 mg orally once daily and was continued until disease progression or unacceptable toxicity. Of those who were treated with a BTK inhibitor, 77% of patients discontinued due to refractory or progressive disease.

In the phase 2 portion of the trial, researchers determined that the ORR was 72% (95% CI, 63-80) and median DOR was 12.2 months (95% CI, 9.3-14.7).

In the trial, the most common adverse reactions were fatigue, bruising, cough, musculoskeletal pain, COVID-19, diarrhea, pneumonia, abdominal pain, dyspnea, hemorrhage, edema, nausea, pyrexia, and headache. Serious infections occurred in 32% of patients, including fatal infections in 10% of patients.

The recommended pirtobrutinib dose is 200 mg orally once daily until disease progression or unacceptable toxicity is observed.



FDA grants accelerated approval to pirtobrutinib for chronic lymphocytic leukemia and small lymphocytic lymphoma. News release. US Food and Drug Administration; December 1, 2023. Accessed December 28, 2023.