The most common adverse reactions include fatigue, musculoskeletal pain, diarrhea, edema, dyspnea, pneumonia, and bruising.[4] The most common adverse reactions when used to treat
chronic lymphocytic leukemia or small
lymphocytic leukemia include fatigue, bruising, cough, musculoskeletal pain, COVID-19, diarrhea, pneumonia, abdominal pain, dyspnea, hemorrhage, edema, nausea, pyrexia, and headache.[6]
Pirtobrutinib was approved for medical use in the United States in January 2023,[4][7][8][9] and in the European Union in November 2023.[2]
Medical uses
In the US, pirtobrutinib 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.[1][10] In December 2023, the US
Food and Drug Administration (FDA) expanded the indication for pirtobrutinib to include the treatment of adults with chronic lymphocytic leukemia or small lymphocytic leukemia.[6][11]
In the EU, pirtobrutinib is indicated for the treatment of mantle cell lymphoma.[2]
Mechanism of action
B cells are white cells of the
lymphocyte subtype that produce antibodies, but when some of them grow uncontrollably they can be a cause of cancer. A key enzyme in B cell stimulation and survival is BTK, and pirtobrutinib inhibits BTK in a way that is different from the prototypical BTK inhibitor
ibrutinib by binding in a different way that avoids a genetic change (mutation at active site
cysteine residue C481 in BTK) that can make some tumors less responsive to ibrutinib.[5]
Efficacy was evaluated in BRUIN (NCT03740529), an open-label, multicenter, single-arm trial of pirtobrutinib monotherapy that included 120 participants with MCL previously treated with a Bruton's tyrosine kinase (BTK) inhibitor.[4] Participants had a median of three prior lines of therapy, with 93% having two or more prior lines.[4] 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.[4]
Efficacy was evaluated in BRUIN (NCT03740529], an open-label, international, single-arm, multicohort trial that included 108 participants with chronic lymphocytic leukemia or small lymphocytic lymphoma previously treated with at least two prior lines of therapy, including a Bruton's tyrosine kinase (BTK) inhibitor and a
B-cell lymphoma-2 (BCL-2) inhibitor.[6] Participants received a median of five prior lines of therapy (range: 2 to 11).[6] Seventy-seven percent of participants discontinued the last BTK inhibitor for refractory or progressive disease.[6] Pirtobrutinib was administered orally at 200 mg once daily and was continued until disease progression or unacceptable toxicity.[6]
Society and culture
Legal status
In April 2023, the
Committee for Medicinal Products for Human Use (CHMP) of the
European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a conditional marketing authorization for the medicinal product Jaypirca, intended for the treatment of relapsed or refractory mantle cell lymphoma (MCL).[13] The applicant for this medicinal product is Eli Lilly Nederland B.V.[13] Pirtobrutinib was approved for medical use in the European Union in November 2023.[2]
^"Jaypirca Product information". Union Register of medicinal products. 31 October 2023.
Archived from the original on 22 November 2023. Retrieved 22 November 2023.
^
ab"Jaypirca: Pending EC decision". European Medicines Agency. 26 April 2023.
Archived from the original on 26 April 2023. Retrieved 27 April 2023. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
Further reading
Mato AR, Woyach JA, Brown JR, Ghia P, Patel K, Eyre TA, et al. (July 2023). "Pirtobrutinib after a Covalent BTK Inhibitor in Chronic Lymphocytic Leukemia". The New England Journal of Medicine. 389 (1): 33–44.
doi:
10.1056/NEJMoa2300696.
PMID37407001.
S2CID259358462.
External links
"Pirtobrutinib". National Cancer Institute. 16 February 2023.