Acalabrutinib treatment in relapsed/refractory primary cutaneous diffuse large B cell lymphoma, leg type. Case report.

Background: Primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT), is a rare subset of primary cutaneous lymphoma known for its aggressive behavior, poor prognosis, and limited treatment options, particularly in the relapsed or refractory setting. We report a case of a patient diagnosed with PCDLBCL-LT who achieved a clinically significant response and sustained remission for seven months with acalabrutinib, a covalent inhibitor of Bruton's tyrosine kinase (BTK), before disease progression. Case presentation: An 88-year-old woman presented with a rapidly enlarging ulcerated lesion on the left lower leg. Histopathological and immunohistochemical analyses confirmed the diagnosis of PCDLBCL-LT. She was treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemoimmunotherapy, followed by external beam radiation therapy (RT). These interventions resulted in only a partial response, and the disease progressed within several months. The patient was receiving direct oral anticoagulant (DOAC) therapy for left lower limb deep vein thrombosis, and she also had a history of hypertension. Considering the increased risk of major bleeding associated with DOAC use and the elevated risk of cardiovascular adverse events previously reported with ibrutinib, an alternative BTK inhibitor was considered. Accordingly, she was initiated on acalabrutinib at a dose of 100 mg orally twice daily. The patient exhibited a rapid and robust clinical response, with complete resolution of cutaneous lesions and sustained remission lasting seven months. Ultimately, the disease progressed, and given her advanced age and overall poor performance status, she was transitioned to hospice care. She subsequently died 14 months after initiating acalabrutinib. Conclusion: This report documents the first known case of successful treatment of relapsed/refractory PCDLBCL-LT with acalabrutinib. Despite advanced age and poor performance status, the patient experienced rapid symptom resolution and durable remission without treatment-related adverse events. These findings suggest that BTK inhibitors may represent a promising therapeutic approach for PCDLBCL-LT, either as monotherapy or in combination with anti-CD20 antibodies. Further investigation into novel targeted therapies is urgently needed for this rare and aggressive lymphoma subtype.