ABSTRACT
For patients with classical hairy cell leukemia (HCL) standard treatment options such as purine analogues (PA) achieve a durable response, but are associated with severe immunosuppression. In particular, PAs cause long-lasting depletion of CD4+-lymphocytes. The BRAF inhibitor vemu-rafenib is effective in HCL but its use in first line treatment is currently limited to select clinical situations such as active infection. There is a lack of clinical data on the impact of BRAF inhibitors on immune function or response to vaccines in HCL. Here, we report the use of vemurafenib in four patients with HCL during the coronavirus disease 2019 (COVID-19) pandemic with detailed immune monitoring during treatment. All patients responded to BRAFi with normalization of peripheral blood counts. None of the patients developed neutropenia or severe infection. We observed stable CD4+ and CD8+ T-lymphocyte counts while receiving vemurafenib (median treatment duration 131 days). Immunoglobulin levels were normal in all patients without decline. 3 out of 4 patients received the SARS-CoV-2 vaccination (Pfizer-BioNTech) during vemuraf-enib treatment. The IgG antibody levels against the spike-protein of SARS-CoV-2 were detectable in 3 out of 3 patients (2-12 weeks after the second vaccination). Our findings suggest that BRAF inhibitors have limited effect on cellular and humoral immune function. The findings may support the use of BRAF inhibitors during the current pandemic to avoid the potentially detrimental effects of PA and thus minimize COVID-19 related morbidity and mortality in patients without SARS-CoV-2 vaccination.