Pitobrutinib in the treatment of mantle cell lymphoma

On January 27, 2023, the U.S. Food and Drug Administration (FDA) granted accelerated approval to pirtobrutinib (trade name Jaypirca) for the treatment of mantle cell lymphoma that has relapsed or is refractory after at least two systemic therapies (including BTK inhibitors).

The drug's efficacy was evaluated in theBRUIN trial. BRUIN was an open-label, multicenter, single-arm study of pitobrutinib monotherapy in 120 patients with mantle cell lymphoma who had previously received BTK inhibitor therapy. The average number of prior lines of therapy among these patients was 3, and 93% of patients had received at least 2 lines of prior therapy. Among them, 83% of patients discontinued their last BTK inhibitor due to refractory or progressive disease. In the trial, patients received 200 mg of pitobrutinib orally once daily until disease progression or unacceptable toxicity.

The study's primary efficacy endpoints include overall response rate and duration of response, which were assessed by an independent review committee using the Lugano criteria. The results showed that the overall response rate was 50%, of which the complete response rate was 13%. The estimated median duration of response was 8.3 months, and the 6-month duration of response rate was 65.3%.

In terms of safety, more than15% of patients with mantle cell lymphoma reported common adverse reactions such as fatigue, musculoskeletal pain, diarrhea, edema, dyspnea, pneumonia and bruising. In addition, more than 10% of patients developed grade 3 or 4 laboratory abnormalities, mainly involving decreases in neutrophil count, lymphocyte count, and platelet count. Therefore, the prescribing information specifically mentions warnings and precautions regarding infection, bleeding, cytopenias, atrial fibrillation and flutter, and second primary malignancies.

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Reference: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-disco-burst-edition-fda-approvals-jaypirca-pirtobrutinib-relapsed-or-refractory-mantle-cell