Zanubrutinib as upfront treatment in de-novo B-cell prolymphocytic leukemia: the case of two elderlies.

B-cell prolymphocytic leukemia (B-PLL) is a rare lymphoproliferative disorder characterized by splenomegaly, lymphocytosis, and poor prognosis. Treatment options are limited, with modest responses to chemo-immunotherapy. We present two elderly patients with B-PLL treated with Zanubrutinib, a second-generation BTK inhibitor, achieving good disease response and tolerance. Both had TP53 deletion/mutations and high-risk complex karyotype. They obtained partial remission with normalization of hematologic parameters and spleen size. Given the rarity of the disease, further studies are needed to define treatment strategies, but Zanubrutinib appears to be a promising drug in this rare orphan drug disease.