Pralatrexate Is Effective in Cytotoxic Cutaneous T-cell Lymphomas Open Access

• Pralatrexate exhibited high efficacy in cytotoxic CTCL, with an ORR of 100% and a CR rate of 67%.

• Pralatrexate showed durable activity in cytotoxic CTCL, with a median PFS of 5.6 months and OS not reached.

Cytotoxic cutaneous T-cell lymphomas (CTCL) are a heterogeneous group of T-cell lymphomas with variable prognoses and no standard of care. We identified patients with primary cutaneous CD8-positive aggressive epidermotropic cytotoxic T-cell lymphoma (CD8+ PCAETL), primary cutaneous gamma-delta T-cell lymphoma (PCGDTL) and subcutaneous panniculitis-like T-cell lymphoma (SPTCL) who were treated with at least one 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 weeks (range 8-43). The overall response rate was 100%, with 12 (67%) achieving complete response. Median progression-free and overall survival was 5.6 months and not reached, respectively. Among CR patients, 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.