Sp06 | Efficacy of Zanubrutinib in Combination With Romiplostim for Evans Syndrome in a Patient With Chronic Lymphocytic Leukemia During Venetoclax Treatment
Year: 2025
Type: article
Abstract: Introduction: Chronic Lymphocytic Leukemia (CLL) is the most common leukemia in Western countries, with age-related incidence and clinical heterogeneity. Evans Syndrome (ES), defined by the concurrent occurrence of immune thrombocytopenia (ITP) and autoimmune hemolytic anemia (AIHA), is a rare immune disorder often associated with lymphoproliferative diseases and potentially fatal outcomes. Management relies on expert consensus due to the lack of randomized trials. Standard CLL therapies include BTK inhibitors (BTKi) and the BCL2 inhibitor Venetoclax, often with anti-CD20 antibodies. When CLL progression is associated with immune cytopenias, immunosuppressive therapy is used, with CLL-directed treatment in refractory cases. To date, no reports have described ITP onset following Venetoclax in a patient with prior AIHA successfully treated with Zanubrutinib. Patients and Methods: We report the case of a 75-year-old man diagnosed in 2019 with asymptomatic CLL who, in 2021, developed steroid- and IVIG-refractory warm AIHA, treated with Bendamustine-Rituximab, achieving partial response. In July 2024, he showed rapid lymphocytosis progression (DT <2 months), splenomegaly (23 cm), thrombocytopenia (PLT 86×10⁹/L), and constitutional symptoms (Rai IV/Binet C). FISH was negative; IGHV unmutated, TP53 wild-type, CLL-IPI 6. Venetoclax-Rituximab (Murano protocol) was started. In week 2 of ramp-up, the patient developed spontaneous ecchymoses and gingival bleeding. Labs showed PLT 0×10⁹/L, Coombs-positive tests, Hb 10.7 g/dL, and a positive SARS-CoV-2 swab. Steroids and IVIG were ineffective. After swab negativization, Rituximab 375 mg/m² was administered weekly ×4 without response. He was referred to our ITP hub. Results: Romiplostim (Rom) was initiated at 3 μg/kg/week and increased by 2 μg/kg/week; Zanubrutinib (Zanu) 160 mg BID was added in week 2. Platelet and hemoglobin normalization occurred within 4 weeks. After 6 months, BTKi was continued at full dose and Rom reduced to 5 μg/kg/week. A 10-day BTKi interruption led to PLT drop (11×10⁹/L), reversed after Zanu reintroduction. The patient has since maintained a complete hematologic response with no adverse events (fig.1). Conclusion: TPO-RAs are effective in ITP. However, when ITP is secondary to CLL, targeting the underlying disease is crucial. BTKi have shown efficacy in ITP, as highlighted in the LUNA3 trial. This case supports the safety and efficacy of combining BTKi and TPO-RAs in refractory secondary ITP.
Institution: Ospedale Garibaldi
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7093122895
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