Pirtobrutinib Granted Accelerated Approval for Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma

Chronic lymphocytic leukemia.

The FDA has granted accelerated approval to pirtobrutinib (Jaypirca®, Eli Lilly and Company) for adults with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who have received at least two prior lines of therapy, including a Bruton tyrosine kinase (BTK) inhibitor and a B-cell lymphoma 2 (BCL-2) inhibitor.  

Why it matters: “Patients with CLL or SLL have poor outcomes after the failure of covalent BTK inhibitor treatment, and new therapeutic options are needed,” wrote Anthony Mato, MD, MS,Hematology and Oncology Specialist at Cayuga Cancer Center, and colleagues, in their published results of the BRUIN trial (NCT03740529), on which approval was based. “Pirtobrutinib, a highly selective, noncovalent BTK inhibitor, was designed to reestablish BTK inhibition.”

What they studied: Safety and efficacy were studied in the phase 1/2 international, single-arm, open-label BRUIN trial which enrolled 108 patients with CLL or SLL who had previous treatment with at least two lines of therapy, including a BTK inhibitor and a BCL-2 inhibitor. Patients were given 200 mg of pirtobrutinib orally, once daily. Treatment continued until disease progression or unacceptable toxicity.

The primary end points measured were overall response rate and duration of response as assessed by an independent review committee using 2018 International Workshop on CLL (iwCLL) criteria.

What they found: The overall response rate with pirtobrutinib was seen at 72%, and the median duration of response was 12.2 months.

What to know:

  • Patients had received a median of five prior lines of therapy
  • Of those enrolled, 77% discontinued their last BTK inhibitor for refractory or progressive disease
  • All responses seen were partial responses

Adverse events: The most common adverse events experienced by ≥20% of those being treated with pirtobrutinib, excluding laboratory abnormalities, were fatigue, bruising, cough, musculoskeletal pain, COVID-19, diarrhea, pneumonia, abdominal pain, dyspnea, hemorrhage, edema, nausea, pyrexia, and headache. Grade 3 or 4 laboratory abnormalities experienced by ≥10% of patients were decreased neutrophil counts, anemia, and decreased platelet counts. Serious infections occurred in 32% of patients, including fatal infections in 10% of patients. The prescribing information includes warnings and precautions for infections, hemorrhage, cytopenias, cardiac arrhythmias, and secondary primary malignancies.

Conclusion: “In this trial, pirtobrutinib showed efficacy in patients with heavily pretreated CLL or SLL who had received a covalent BTK inhibitor,” concluded Dr. Mato and colleagues.

Instructions: The recommended dosage is 200 mg of pirtobrutinib orally, once daily until disease progression or unacceptable toxicity.

For More Information

Mato AR, Woyach JA, Brown JR, et al (2023). Pirtobrutinib after a covalent BTK inhibitor in chronic lymphocytic leukemia. N Engl J Med, 389(1):33-44. DOI:10.1056/NEJMoa2300696

Clinicaltrials.gov (2023). A study of oral LOXO-305 in patients with previously treated CLL/SLL or NHL. NLM identifier: NCT03740529.

Jaypirca® (pirtobrutinib) prescribing information (2023). Eli Lilly and Company. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/216059s001lbl.pdf

US Food and Drug Administration (2023). FDA grants accelerated approval to pirtobrutinib for chronic lymphocytic leukemia and small lymphocytic lymphoma. Available at: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-pirtobrutinib-chronic-lymphocytic-leukemia-and-small-lymphocytic

Image credit: Ed Uthman. Licensed under CC BY-SA 2.0

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