TCL-320 Single Institution Experience of Pembrolizumab for Patients with Relapsed or Refractory Mycosis Fungoides or Sézary Syndrome

Mycosis fungoides (MF) and Sézary syndrome (SS) are the most common subtypes of cutaneous T-cell lymphomas (CTCLs). Clinical trials show promising efficacy of pembrolizumab in treating these lymphomas. However, real-world evidence is limited. A single-center, retrospective observational study of CTCL patients receiving pembrolizumab from December 2017- December 2023 was performed. Global treatment response was determined using 2022 consensus criteria. Treatment toxicity was determined using CTCAE v5.0 criteria. Overall survival (OS) and progression-free survival (PFS) were coprimary endpoints and assessed using Kaplan-Meier log-rank analysis and Cox proportional hazard multivariable regression methods. Twenty-nine patients with CTCL were identified, 10 (34%) with SS and 19 (66%) with MF. Median age was 66 (40-85). Sixteen (55%) patients were male and 23 (79%) were Caucasian. Twenty-three (79%) had ECOG 0-1. Six (21%) patients had early-stage and 23 (79%) had advanced-stage disease. Seven (24%) had history of large cell transformation. Median number of prior treatments was 3 (1-8), with 13 (45%) receiving HDACi, and 10 (34%) receiving mogamulizumab. Overall response rate evaluable in 28 (97%) patients was 46.4% (CR, 4 [31%]; PR, 9 [69%]) with median duration of response of 11.2 months. Four (14%) patients received pembrolizumab in combination with another agent and 6 (21%) received concurrent radiotherapy (n=4 electron beam; n=2 photon-based). Median follow-up was 23.4 months with mPFS of 18.2 months and mOS of 34.2 months. Worse survival was associated with prior HDACi treatment ( P = .006), CTCL stage ( P = .0001), and best response to treatment of SD/PD ( P = .002). Thirteen (45%) patients had immune-related adverse events (IRAEs), most commonly dermatologic (38%), endocrine (31%), or gastrointestinal (23%). Most IRAEs (11/13, 84.6%) were grade 1-2 and steroids were required in 4/13 (30.7%). Most IRAEs (9/13, 69%) resolved at subsequent follow-up. Therapy was discontinued in 26 (89.6%) patients, most commonly due to progression (58%), non-treatment-related illness (12%), or intolerance (12%). Fifteen (52%) patients were alive at last follow-up, with 3 (10%) patients continuing treatment. Pembrolizumab is a well-tolerated treatment modality with promising activity in heavily pretreated relapsed/refractory MF/SS. Efforts to define clinicopathological markers that predict response to pembrolizumab in CTCL are necessary and ongoing.