Final results of UK NCRI phase II trial of pembrolizumab and radiotherapy in cutaneous T cell lymphoma

Abstract

The outlook for patients with advanced cutaneous T-cell lymphomas (CTCL); mycosis fungoides (MF) and Sézary syndrome (SS) remains poor and most systemic treatments provide short-lived remissions. Immunotherapy has provided a major cancer breakthrough, and the PORT trial was designed to investigate the efficacy of Pembrolizumab and whether the addition of Radiotherapy (RT) could further enhance systemic “abscopal” anti-tumour immune responses. Pembrolizumab followed by 12Gy in 3 fractions RT to a localized lesion was investigated in a single-arm, multicentre phase II trial for relapsed/refractory CTCL. Primary endpoint was overall response rate (ORR), secondary endpoints included duration of response (DOR), abscopal response, progression-free survival (PFS), overall survival (OS). 46 patients (41 MF, 5 SS) were registered, median age 63 (24-83), 24% stage IV. Median follow-up was 24.8 months. 24% of patients remained on treatment for >1 year whilst 57% received <9 infusions (all stage IV disease / SS). Although the primary endpoint was not met, ORR 20%, best ORR 26% (95% CI 14-41), DOR rates at 1 and 2-years were 75% (95% CI 41-91) and 57% (95% CI 25-80) resulting in median PFS of 12.6 months and abscopal mSWAT scores suggested a RT induced “abscopal” effect. The treatment was well tolerated with infections most common (17%), 21 deaths were reported (11 CTCL, 3 Covid- 19, 1 Sepsis, 6 Other). 2-year OS was 62%. Pembrolizumab in combination with RT resulted in durable clinical responses with evidence of a RT induced abscopal effect in a subset of relapsed CTCL patients.