In a nutshell
This study tested the safety and effectiveness of pirtobrutinib (LOXO-305) in the treatment of patients with B cell leukemia-lymphoma. The authors found that pirtobrutinib was safe and had promising effectiveness in these patients.
B cells are a type of cell of the immune system. Some lymphomas and leukemias such as non-Hodgkin lymphomas (NHL) and chronic lymphocytic leukemia (CLL) affect these cells. Targeted therapies such as Bruton's tyrosine kinase (BTK) inhibitors have improved the outcomes of patients with B-cell blood cancers. However, many patients develop resistance or intolerable side effects to current BTK inhibitors. Therefore, newer agents are needed for these patients.
Pirtobrutinib is a new BTK inhibitor in clinical trials. The safety and effectiveness of pirtobrutinib in patients with previously treated B-cell leukemia/lymphoma are still under investigation.
Methods & findings
323 patients with leukemia/lymphoma were enrolled in the study. All patients had at least 2 previous lines of therapy. Pirtobrutinib was given to all patients. Seven dose levels were given as tablets once daily in 28-day cycles. The recommended dose was 200 mg per day. The average follow-up period was 6 months.
63% of the patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) had a response to pirtobrutinib therapy. 52% of patients with mantle cell lymphoma (MCL) and 68% with Waldenström macroglobulinemia (WM; lymphoplasmacytic lymphoma) had a response to pirtobrutinib. This was similar for patients that had previously been treated with another BTK inhibitor and those who were not.
88% of patients with CLL/SLL, 57% with MCL, and 77% with WM were still on pirtobrutinib treatment at follow-up.
Most side effects were mild. The most common side effects were fatigue (20%) and diarrhea (17%).
The bottom line
The authors found that pirtobrutinib was effective and safe for the treatment of B-cell leukemia/lymphoma.
The fine print
This was a small phase 1/2 clinical trial. The follow-up period was very short. Additional studies are needed to determine whether the efficacy of pirtobrutinib is long-term. This study was funded by Loxo Oncology, the manufacturer of pirtobrutinib.
Published By :
Lancet (London, England)
Mar 06, 2021