Key Points
• Source: EJHaem
• Relevance: “The hematopoietic cell kinase (HCK) regulates BTK activation and represents a potential therapeutic target in Waldenstrom macroglobulinemia (WM). We investigated dasatinib, a potent HCK inhibitor, in patients with WM progressing on ibrutinib.”
• Harvard medical school researchers treated a small cohort with 100 mg dasatinib 100 mg PO qD in 4-week cycles. One patient received 1 month of therapy, and 2 patients received 5 months of therapy. One patient had the dose decreased secondary to volume overload. Lack of response led to termination of the study.
• The authors cited other promising emerging therapies including venetoclax, which was added to the National Comprehensive Cancer Network (NCCN) guidelines as a treatment option for patients with WM who received previous treatment. Furthermore, the noncovalent BTK inhibitor pirtobrutinib could be effective in patients with previously treated B-cell malignancies.
• The authors concluded, “Given the small‐sample size of our pilot study, strong conclusions on the efficacy of dasatinib in WM progressing on ibrutinib cannot be reached. Although our study was not testing a specific hypothesis, we would have hoped for a response rate of at least 50%. After observing stable disease in three participants, we felt attaining such response rate would be unlikely. Dasatinib might not be effective in patients with WM progressing on ibrutinib. Therefore, other approaches to treat patients with WM progressing on covalent BTK inhibitors should be sought.”