A Phase I Trial Assessing the Feasibility of Romidepsin Combined with Brentuximab Vedotin for Patients Requiring Systemic Therapy for Cutaneous T-Cell Lymphoma

Barta, S. K.; Feldman, T. A.; DeSimone, J. A.; Kim, E.; Devajaran, K.; Wiest, D.; Fung, H. C. H.; Fisher, R. I.; Tan, C.; Khan, N.

Introduction: While most patients (pts) with cutaneous T-cell lymphoma (CTCL) have an indolent course, survival for stages ≥IIB is usually less than 5 years (Kim YH et al, Arch Dermatol 2003). When an aggressive approach of combination cytotoxic therapies and radiation in CTCL was compared to conservative sequential therapies in newly diagnosed pts, the increase in response rate with combination therapy was offset by toxicities, and no benefit in disease-free or overall survival was seen (Kaye FS et al, NEJM, 1989). Since then several novel agents have been approved in CTCL, including the CD30-directed antibody-drug conjugate brentuximab vedotin (BV) [in relapsed primary cutaneous ALCL and CD30-expressing mycosis fungoides (MF)], and HDAC inhibitors (HDACi). However, response rates of single agents are modest. Tolerable and more efficacious therapies are needed, including rational combinations of active biological agents. Evidence suggests that HDAC inhibition may upregulate CD30 expression (Hasanali ZS et al, Sci Transl Med 2015), supporting the combination of the HDACi romidepsin (R) with Brentuximab vedotin (BV) in pts with CTCL. Methods: In this multicenter phase I clinical trial, pts age ≥18 with stage ≥IB CTCL, good organ function, ECOG PS≤2,