FDA Grants Accelerated Approval to Pirtobrutinib for Relapsed or Refractory Mantle Cell Lymphoma

On January 27, 2023, the U.S. Food and Drug Administration approved Pirtobrutinib for adult patients with histologically confirmed relapsed or refractory Mantle cell lymphoma intolerant to two or more standard therapies, one of which must be Bruton’s Kinase (BTK) inhibitor.

 

Study ID number: NCT03740529

 

Approval was based on the BRUIN study, an open-label, multicenter, single-arm trial that included 120 patients with Mantle cell lymphoma — 93% of patients had received at least two lines of standard therapies and had relapsed or proven to be not responding. One of these therapies included either ibrutinib, acalabrutinib, or zanubrutinib. Pirtobrutinib was given 200 mg once daily until disease progression or unacceptable toxicity.

 

Efficacy was established based on the overall response rate (ORR) and duration of response (DOR). The ORR was 50% (95% CI: 41, 59), with a complete response rate of 13%. The estimated median DOR was 8.3 months (95% CI: 5.7, NE), and the estimated DOR rate at six months was 65.3% (95% CI: 49.8, 77.1).

 

The most observed adverse effects included fatigue, musculoskeletal pain, diarrhea, edema, dyspnea, and laboratory abnormalities, among others. Notably, prescribing information includes warnings and precautions for infections, bleeding, cytopenia, atrial fibrillation and flutter, and second primary malignancies.