P115 | CUTANEOUS INVOLVEMENT IN CHRONIC LYMPHOCYTIC LEUKEMIA: REAL-WORLD OUTCOMES WITH VENETOCLAX-OBINUTUZUMAB AT FONDAZIONE POLICLINICO UNIVERSITARIO AGOSTINO GEMELLI IRCCS.

Introduction: Cutaneous manifestations are rare in patients with chronic lymphocytic leukaemia (CLL) and may result from either direct leukemic infiltration or the general predisposition of CLL patients to secondary conditions. Leukaemia cutis (LC), caused by skin infiltration of leukemic cells, is seen in 4–20% of cases and is diagnosed through clinical, histological, and immunophenotypic features. LC typically regresses with disease remission. Here we describe two CLL cases with LC successfully treated with Venetoclax-Obinutuzumab (VO). Methods: In May 2022, a 58-year-old man with CLL developed multiple purplish nodules (1.5–2 cm) on the earlobes and on the pinnae. Blood tests showed lymphocytosis. In January 2024, a 53-year-old woman in CLL follow-up presented with painful, wine-red nodular lesions on the nose and ears, hypertrophy of Waldeyer’s ring, and nodular plaques on the legs, resembling vasculitis lesions. CT scan revealed lymphadenopathy without splenomegaly. Both patients underwent dermatological exams and biopsies. Their features are summarized in Table 1. Results: At our centre “Fondazione Policlinico A. Gemelli”, 2 of 26 naïve patients (7.7%) treated with VO presented skin involvement in the form of leukaemia cutis. In both, cutaneous lesions showed Ki67 > 45% and high BCL2 expression. Initial steroid therapy was ineffective. Due to disease progression and new skin lesions, both began VO therapy, based on their CLL biological profile, and obtained resolution of the cutaneous infiltration. Discussion: LC is rare at CLL onset and typically emerges later in the disease. Head and neck are common sites, as seen in our patients. Lesions tend to resolve with hematologic remission. Its prognostic significance and its optimal treatment remain unclear. Some studies have shown LC response to conventional chemoimmunotherapy or newer agents like BTKi or BCL2 inhibitors plus anti-CD20 antibodies. In our series, both patients had early LC resolution with VO. Despite not strictly meeting IWCLL treatment criteria, high Ki67 and BCL2 levels, suggesting more aggressive disease biology but also potential for better response to VO, guided the clinical choice of therapy. Conclusion: Our experience supports the efficacy of VO in treating CLL with atypical skin involvement. Cutaneous lesions may regress alongside or even before hematologic remission. Broader data collection on LC treated with Venetoclax-based regimens may clarify outcomes and guide management.