FDA Approves Pirtobrutinib for Relapsed/Refractory Mantle Cell Lymphoma

On January 27, 2023, the Food and Drug Administration (FDA) granted accelerated approval to pirtobrutinib, a non-covalent BTK inhibitor, for relapsed/refractory mantle cell lymphoma (MCL) after at least 2 lines of systemic therapy, including a BTK inhibitor.

The efficacy was evaluated in BRUIN, an open-label, multicenter, single-arm trial of pirtobrutinib monotherapy that included 120 patients with MCL previously treated with a BTK inhibitor. Patients had a median of 3 prior lines of therapy, with 93% having 2 or more prior lines. The most common prior BTK inhibitors received were ibrutinib (67%), acalabrutinib (30%), and zanubrutinib (8%); 83% had discontinued their last BTK inhibitor due to refractory or progressive disease.

In this trial 200 mg pirtobrutinib was administered orally once daily and was continued until disease progression or unacceptable toxicity. The main efficacy measures were overall response rate (ORR) and duration of response (DOR), as assessed by an independent review committee. The ORR was 50% (95% confidence interval [CI], 41 to 59) with a complete response rate of 13%. The estimated median DOR was 8.3 months (95% CI, 5.7 to [not estimable [NE]), and the estimated DOR rate at 6 months was 65.3% (95% CI, 49.8 to 77.1).

The most common adverse reactions (≥15%) reported were fatigue, musculoskeletal pain, diarrhea, edema, dyspnea, pneumonia, and bruising. Grade 3/4 laboratory abnormalities in ≥10% of patients were 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.

Source:

FDA grants accelerated approval to pirtobrutinib for relapsed or refractory mantle cell lymphoma. Press Release. The US Food and Drug Administration. Published online January 27, 2023. Accessed January 27, 2023. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-pirtobrutinib-relapsed-or-refractory-mantle-cell-lymphoma