Pirtobrutinib, sold under the brand name Jaypirca, is an anticancer medication that is used to treat mantle cell lymphoma, CLL and small lymphocytic leukemia.
Routes of administration-oral.
It inhibits B cell lymphocyte proliferation and survival by binding and inhibiting Bruton’s tyrosine kinase (BTK).
In refractory/recurrent CLL pirtobrutimib monotherapy had an overall response rate of 75% and the medium progression free survival of 19.6 months.
It is a non-covalent BTK inhibitor that binds to sites that are distinct from those that covalent BTK inhibitors bind.
Its high selectivity for BK translates to minimal toxicity.
The most common adverse reactions include fatigue, musculoskeletal pain, diarrhea, edema, dyspnea, pneumonia, and bruising.
Grade 3 or 4 laboratory abnormalities include decreased neutrophil counts, lymphocyte counts, and platelet counts.
It is indicated to treat relapsed or refractory mantle cell lymphoma after at least two lines of systemic therapy, including a Bruton’s tyrosine kinase (BTK) inhibitor.
Pirtobrutinib inhibits BTK in a way that is different from the prototypical BTK inhibitor ibrutinib by binding in a different way that avoids a mutation at active site cysteine residue C481 in BTK, that can make some tumors less responsive to ibrutinib.
Efficacy was evaluated in BRUIN, an open-label, multicenter, single-arm trial of pirtobrutinib monotherapy that included 120 participants with MCL previously treated with a BTK inhibitor.
Participants had a median of three prior lines of therapy, with 93% having two or more prior lines.
The most common prior BTK inhibitors received were ibrutinib (67%), acalabrutinib (30%), and zanubrutinib (8%); 83% had discontinued their last BTK inhibitor due to refractory or progressive disease.
Approved for refractory CLL and small lymphocytic lymphoma.