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The FDA has granted (Jaypirca), a non-covalent or reversible Bruton's tyrosine kinase (BTK) inhibitor, for the treatment of relapsed or refractory mantle cell lymphoma (MCL) after at least two prior lines of systemic therapy, including a BTK inhibitor.

Pirtobrutinib is the first BTK inhibitor of any kind specifically approved for patients with MCL that has been previously treated with a covalent BTK inhibitor, according to Eli Lilly, the drug's developer.

Approval was based on data from a subset of 120 patients with MCL from the open-label, single-arm , who had previously received a covalent BTK inhibitor.

The approval "represents an important advance for patients with relapsed or refractory MCL, who currently have limited options and historically have had a poor prognosis following discontinuation of treatment with a covalent BTK inhibitor," said BRUIN investigator Michael Wang, MD, of the University of Texas MD Anderson Cancer Center in Houston, .

Patients in the multicenter trial were treated with pirtobrutinib 200 mg once daily until disease progression or unacceptable toxicity. The overall response rate among those 120 MCL patients was 50% (95% CI 41-59), with complete responses achieved in 13%. Median time to response was 1.8 months (95% CI 0.8-4.2), with an estimated median duration of response of 8.3 months (95% CI 5.7-NE), and an estimated duration of response rate at 6 months of 65.3% (95% CI 49.8-77.1).

"These data indicate that Jaypirca can provide efficacy in patients previously treated with a covalent BTK inhibitor, potentially extending the time patients may benefit from BTK inhibition therapy," said Wang. "Jaypirca offers a new approach to targeting the BTK pathway following treatment with a covalent BTK inhibitor and has the potential to meaningfully impact the treatment paradigm for relapsed and refractory MCL patients."

Regarding safety, in the full BRUIN study population of 583 patients with a variety of hematologic malignancies, the most common adverse reactions to pirtobrutinib (≥20% of patients) were decreased neutrophil count, decreased hemoglobin, decreased platelet count, fatigue, musculoskeletal pain, decreased lymphocyte count, bruising, and diarrhea.

Among those patients with MCL (of whom 36% were exposed to pirtobrutinib for 6 months or longer, and 10% for at least a year), adverse reactions led to dose reductions in 4.7%, treatment interruption in 32%, and permanent discontinuation of the therapy in 9% of patients.

Common adverse events (≥15%) in patients with MCL were fatigue, musculoskeletal pain, diarrhea, edema, dyspnea, pneumonia, and bruising. Grade 3/4 laboratory abnormalities occurring in ≥10% of patients included decreased neutrophil counts, lymphocyte counts, and platelet counts.

The prescribing information includes warnings and precautions for infections, hemorrhage, cytopenias, atrial fibrillation and flutter, and second primary malignancies.

A confirmatory study, , is currently enrolling patients. The phase III trial will compare pirtobrutinib to investigator's choice of ibrutinib (Imbruvica), acalabrutinib (Calquence), or zanubrutinib (Brukinsa) for MCL patients who have received one or more prior lines of systemic therapy, but are BTK inhibitor naive.

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