Pralatrexate is effective in cytotoxic cutaneous T-cell lymphomas.

Cytotoxic cutaneous T-cell lymphomas (CTCLs) are a heterogeneous group of T-cell lymphomas with variable prognoses and no standard of care. We identified patients with primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma (CD8+ PCAETL), primary cutaneous γδ T-cell lymphoma (PCGDTL), and subcutaneous panniculitis-like T-cell lymphoma (SPTCL), who were treated with ≥1 dose of pralatrexate between 2015 and 2024 at the University of Washington/Fred Hutchinson Cancer Center. Eighteen patients met criteria, 3 with CD8+ PCAETL, 6 with PCGDTL, and 9 with SPTCL. The median number of prior systemic therapies was 1 (range, 0-4), and the median pralatrexate treatment duration was 14 (range, 8-43) weeks. The overall response rate was 100%, with 12 (67%) achieving complete response (CR). Median duration of progression-free survival and overall survival was 5.6 months and not reached, respectively. Among patients who achieved CR , the median response duration was 22 months. At a median follow-up of 45 months, 6 (33%) patients remain in sustained remission. This retrospective analysis is the first to evaluate pralatrexate's efficacy in this aggressive disease population, demonstrating its effectiveness and association with durable responses in cytotoxic CTCL.