Pirtobrutinib Demonstrates Activity in Patients with MCL Pretreated with a Covalent BTK Inhibitor

Pirtobrutinib demonstrated clinically meaningful and durable antitumor activity in patients with mantle cell lymphoma (MCL) who previously received a covalent Bruton’s tyrosine kinase (BTK) inhibitor. The results of the phase II study were presented at the 65th ASH Annual Meeting and Exposition.

Pirtobrutinib is a non-covalent (reversible) BTK inhibitor that inhibits both wild-type and C481-mutant BTK.

The open-label, multicenter study was conducted in China and included patients with relapsed or refractory B-cell malignancies who had received a prior covalent BTK inhibitor. Patients received pirtobrutinib 200 mg until disease progression, unacceptable adverse events, or other reasons for discontinuation.

At data cutoff (April 10, 2023), 39 patients were enrolled: 28 in the primary analysis set and 35 in the efficacy analysis set. In the primary analysis cohort, patients had received a median of three prior therapies (range, 1–8 therapies), the majority of which were chemotherapy (96.4%) and an anti-CD20 antibody (85.7%). The most common reason for discontinuation of a prior covalent BTK inhibitor was disease progression.

Outcomes, per independent review committee, included:

• Overall response rate (ORR), 71.4% (95% CI, 51.3-86.8)
  • Complete response, 14.3% (n=4)
  • Partial response, 57.1% (n=16)
• Median duration of response (DOR), not reached
  • Six-month DOR, 66.02% (95% CI, 39.29-83.14)
• Median progression-free survival, 9.43 months
• Median overall survival, 15.47 months

Outcomes were similar in the efficacy analysis cohort, including an ORR of 62.9% (95% CI, 44.9-78.5) and a six-month DOR of 64.45%.

The safety analysis included 87 patients who were on therapy for a median of 4.2 months. Common any-grade treatment-related adverse events included decreased neutrophil count (40.2%), anemia (31.0%), and increased bilirubin (23.0%). The most common grade ≥3 treatment-related adverse event was decreased neutrophil count (25.3%).

All-grade hemorrhage was observed in 19.5% of patients (n=17), and all-grade hypertension occurred in 5.7% (n=5) of patients. Atrial fibrillation/flutter was not observed. Three patients (3.4%) discontinued treatment due to adverse events, and two (2.3%) experienced treatment-related fatal adverse events.

Reference

Song Y, Yang H, Feng R, et al. Pirtobrutinib, a non-covalent (reversible) BTK inhibitor, in mantle cell lymphoma patients previously treated with a covalent BTK inhibitor: results from a China phase 2 study. Abstract #3636. Presented at the 65th ASH Annual Meeting and Exposition; December 9-12, 2023; San Diego, California.