Pirtobrutinib: A New and Distinctive Treatment Option for B-Cell Malignancies.

Objective: The objective was to evaluate the efficacy/safety of pirtobrutinib in the treatment of B-cell malignancies and distinguish it from other available Bruton's tyrosine kinase (BTK) inhibitors.

Data Sources: A literature search of PubMed (January 2021 through November 2023) and Clinicaltrials.gov was conducted using terms , and Licensing trials of available BTK inhibitors were also reviewed.

Study Selection And Data Extraction: Relevant English-language clinical trials were evaluated.

Data Synthesis: Pirtobrutinib was approved by the US Food and Drug Administration for the treatment of relapsed/refractory mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL) based largely on a phase 1/2 study in B-cell malignancies. Pirtobrutinib demonstrated a 73% overall response rate (ORR) in the CLL population and 58% in MCL. Pirtobrutinib has activity in patients resistant to earlier-generation, covalent BTK inhibitors. In fact, the ORRs were similar in BTK-pretreated and naïve patients. Adverse effects include fatigue, diarrhea, bleeding, and infection. Atrial fibrillation, a class effect of BTK inhibitors, may be less common with pirtobrutinib.

Relevance To Patient Care And Clinical Practice In Comparison With Existing Drugs: Compared with earlier-generation BTK inhibitors, pirtobrutinib is more selective for BTK and binds noncovalently to the receptor. Ongoing studies are evaluating pirtobrutinib's use in multiple B-cell malignancies and comparing it with other BTK inhibitors.

Conclusion: The characteristics of pirtobrutinib render it useful in the treatment of B-cell malignancies no longer responding to a previous BTK inhibitor, and results from ongoing clinical trials may support future expanded use.