Efficacy and manageable toxicity of mogamulizumab in a real-world North American cohort of adult T-cell leukemia/lymphoma (ATLL).

e18603 Background: Adult T-cell leukemia/lymphoma (ATLL), a malignancy of CD4+ T-cells linked to HTLV-1 infection, carries a poor prognosis. Treatment options beyond allogeneic transplantation remain limited. Mogamulizumab, a CCR4-targeting monoclonal antibody, is FDA-approved for relapsed cutaneous T-cell lymphoma and has shown efficacy in Japanese ATLL. However, North American ATLL (NA-ATLL) differs genomically and transcriptionally from Japanese ATLL, potentially driving worse outcomes. To address the limited treatment options for NA-ATLL, this study evaluates mogamulizumab in relapse/refractory NA-ATLL. Methods: Nine patients with relapsed/refractory ATLL treated with mogamulizumab were analyzed. Median age was 63 years (range: 42–77), with 67% Black/African American. Subtypes included acute/leukemic (n=5) and lymphomatous (n=4). Patients had received a median of three prior therapies (range: 1–4). Primary endpoints were overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and adverse event (AE) assessment. OS was compared to historical controls. DNA was isolated from the peripheral blood of thirty-seven ATLL patients from our center and sent to NeoGenomics for mutational analysis via Next Generation Sequencing. Results: Mogamulizumab demonstrated an ORR of 55.6%, with two complete responses and three partial responses. Four patients experienced disease progression. The median number of mogamulizumab infusions administered was 9 (range: 1–14). AEs were infrequent and manageable, including febrile reactions (n=2) and fatigue (n=1). Two patients had prolonged survival after treatment discontinuation, with one showing clonal evolution and loss of a pathogenic mutation. The median OS for the mogamulizumab cohort was 309 days versus 33 days in the historical control group (p=0.0013). These findings highlight the potential of mogamulizumab as an effective and tolerable treatment option in this patient population, warranting further investigation. Conclusions: Our findings highlight the efficacy and tolerability of mogamulizumab in a real-world NA-ATLL cohort, showing improved survival outcomes compared to historical controls. These results support the inclusion of mogamulizumab in the treatment paradigm for heavily pre-treated ATLL patients. Larger prospective studies are warranted to re-explore its potential as monotherapy or in combination regimens in real world settings.