Pirtobrutinib Granted Accelerated Approval for Mantle Cell Lymphoma

Flower cell in mantle cell lymphoma.

The FDA has granted accelerated approval to pirtobrutinib (Jaypirca™, Eli Lilly and Company) for patients with relapsed or refractory mantle cell lymphoma (MCL) following a minimum of two lines of systemic therapy that included a Bruton tyrosine kinase inhibitor (BTKi).

“Pirtobrutinib, a highly selective, non-covalent (reversible) BTKi, inhibits both wildtype and C481-mutant BTK with equal low nanomolar (nM) potency, and has favorable oral pharmacology that enables continuous BTK inhibition throughout the dosing interval regardless of intrinsic rate of BTK turnover,” wrote Michael Wang, MD, Professor in the Department of Lymphoma and Myeloma at MD Anderson Cancer Center, and colleagues, in their updated findings from the BRUIN trial (NCT03740529), on which approval was based, recently presented at the 64th American Society of Hematology (ASH) Annual Meeting in New Orleans. “Pirtobrutinib is well-tolerated and has demonstrated promising efficacy in patients with poor-prognosis B-cell malignancies following prior therapy, including prior covalent BTKi.”

Safety and efficacy were evaluated in the phase 1/2, open-label, single-arm, multicenter trial, in which 120 patients with previously treated MCL with a BTKi received 200 mg of pirtobrutinib orally, once daily until disease progression or unacceptable toxicity. Participating patients had received a median of three prior lines of therapy with a BTKi, including ibrutinib (67%), acalabrutinib (30%), and zanubrutinib (8%). Most patients (83%) had discontinued their previous treatment with a BTKi because they became refractory or experienced disease progression.

The key end points included overall response rate and duration of response, as assessed by an independent review committee using Lugano criteria. Overall response rate was 50.0%, with 13.0% of patients achieving a complete response. The median duration of response was 8.3 months, and the six-month duration of response was estimated at 65.3%.

The most common adverse events experienced by ≥15% of MCL patients were fatigue, musculoskeletal pain, diarrhea, edema, dyspnea, pneumonia, and bruising. Laboratory abnormalities of grade 3 or 4 experienced by ≥10% of patients were decreased neutrophil counts, lymphocyte counts, and platelet counts. Included in the prescribing information are warnings and precautions for infections, hemorrhage, cytopenias, atrial fibrillation and flutter, and second primary malignancies.

“In this updated analysis with additional patients and extended follow-up, pirtobrutinib continues to demonstrate promising and durable efficacy in heavily pretreated relapsed or refractory MCL patients who have been treated with a prior covalent BTKi,” concluded Dr. Wang and colleagues in their abstract presented at ASH. “Pirtobrutinib was well-tolerated with low rates of discontinuation due to drug-related toxicity.”

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

For More Information

Wang M, Shah N, Jurczak W, et al (2022). Efficacy of pirtobrutinib in covalent BTK-inhibitor pre-treated relapsed/refractory mantle cell lymphoma: additional patients and extended follow-up from the phase 1/2 BRUIN study. 64th American Society of Hematology Annual Meeting. Abstract 4218.

Clinicaltrials.gov (2022). 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/2023/216059s000lbl.pdf

US Food and Drug Administration (2023). FDA grants accelerated approval to pirtobrutinib for relapsed or refractory mantle cell lymphoma. Available at: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-pirtobrutinib-relapsed-or-refractory-mantle-cell-lymphoma 

Image credit: SpicyMilkBoy. Licensed under CC BY-SA 4.0


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