Study Evaluates Safety of Long-Term Pirtobrutinib Administration in B-cell Malignancies

Pirtobrutinib “continues to demonstrate a safety profile amenable to long-term administration” in patients with relapsed or refractory B-cell malignancies, according to research presented during the Eleventh Annual Meeting of the Society of Hematologic Oncology.

Catherine Muehlenbein, PhD, of Loxo@Lilly, and colleagues conducted the study because the “long-term safety and tolerability of pirtobrutinib has not yet been reported.”

Researchers Analyze BRUIN Trial Data on Pirtobrutinib

The study included patients with relapsed or refractory B-cell malignancies in the phase I/II BRUIN trial who received pirtobrutinib for at least a year. The researchers evaluated treatment-emergent adverse events (AEs) that occurred in at least 20% of patients and select AEs of interest associated with Bruton’s tyrosine kinase (BTK) inhibitors. They collected data on the cumulative incidence rates of AEs, the median time to onset of the AEs, as well as rates of dose reduction and discontinuation.

Of the 773 patients enrolled in the study at the end of July 2022, 326 (42%) received pirtobrutinib for at least 12 months. The median time on treatment was 19 months for those patients, with 71% remaining on treatment.

The most common treatment-emergent AEs were fatigue, which occurred in 32% of patients, diarrhea in 31%, COVID-19 in 29%, contusion in 26%, cough in 25%, and back pain in 21%. Treatment-emergent AEs that led to dose reduction occurred in 7% of patients, while treatment-emergent AEs that led to discontinuation occurred in 3%. Discontinuation due to a treatment-related AE occurred in 1% of patients and one patient had a fatal treatment-related AE, which was COVID-19 pneumonia.

“Prolonged pirtobrutinib therapy continues to demonstrate a safety profile amenable to long-term administration at the recommended dose without evidence of new or worsening toxicity signals,” Dr. Muehlenbein and colleagues concluded. “The safety and tolerability observed in patients on therapy for ≥12 months was similar to previously published safety analyses on all patients enrolled regardless of follow-up.”

Reference

Muehlenbein C, Coombs C, Shah N, et al. Long-term safety with ≥12 months of pirtobrutinib in relapsed/refractory B-cell malignancies. Abstract CT-166. Presented at the Eleventh Annual Meeting of the Society of Hematologic Oncology; September 6-9, 2023; Houston, Texas.