Pembrolizumab in Relapsed and Refractory Mycosis Fungoides and Sézary Syndrome: A Multicenter Phase II Study

Abstract

PURPOSE To assess the efficacy of pembrolizumab in patients with advanced relapsed or refractory mycosis fungoides (MF) or Sézary syndrome (SS). PATIENTS AND METHODS CITN-10 is a single-arm, multicenter phase II trial of 24 patients with advanced MF or SS. Patients were treated with pembrolizumab 2 mg/kg every 3 weeks for up to 24 months. The primary end point was overall response rate by consensus global response criteria. RESULTS Patients had advanced-stage disease (23 of 24 with stage IIB to IV MF/SS) and were heavily pretreated with a median of four prior systemic therapies. The overall response rate was 38% with two complete responses and seven partial responses. Of the nine responding patients, six had 90% or more improvement in skin disease by modified Severity Weighted Assessment Tool, and eight had ongoing responses at last follow-up. The median duration of response was not reached, with a median response follow-up time of 58 weeks. Immune-related adverse events led to treatment discontinuation in four patients. A transient worsening of erythroderma and pruritus occurred in 53% of patients with SS. This cutaneous flare reaction did not result in treatment discontinuation for any patient. The flare reaction correlated with high PD-1 expression on Sézary cells but did not associate with subsequent clinical responses or lack of response. Treatment responses did not correlate with expression of PD-L1, total mutation burden, or an interferon-γ gene expression signature. CONCLUSION Pembrolizumab demonstrated significant antitumor activity with durable responses and a favorable safety profile in patients with advanced MF/SS.

Blockade of programmed cell death protein 1 (PD-1) in Sézary syndrome reduces Th2 phenotype of non-tumoral T lymphocytes but may enhance tumor proliferation

“…In this study, IHC expression of PD-1, PD-L1, or PD-L2 could not predict response to treatment, but increased PD-L1 expression by both IHC and nanoString analysis upon administration of pembrolizumab was observed. 69 To our knowledge, our study provides the first analysis that consecutively addresses the expression of PD-1 and its ligands in CD4 + malignant and bystander cells in peripheral blood and skin lesions in L-CTCL. Our results demonstrate high heterogeneity in the expression of immune checkpoint molecules, PD-1, PD-L1 and PD-L2, on malignant and nonmalignant CD4 + T cells in the blood and skin of patients with L-CTCL.…”

Combined total skin radiotherapy and immune checkpoint inhibitors: A promising potential treatment for mycosis fungoides and Sezary syndrome

“…In hematologic malignancies, PD‐1 blockade is effective and has a favorable safety profile. With respect to relapsed or refractory MF/SS, pembrolizumab was associated with an ORR of 38 % (complete response: 4 %) and a two‐year progression‐free survival of 69 % . The ORR associated with the immune checkpoint inhibitor nivolumab was 15 % .…”

Innovative Therapeutic Approaches in Primary Cutaneous B Cell Lymphoma

“…However, the biological function of PD-1/PD-L1 expression is less clear in lymphocytic malignancies. In pCTCL, where the meaning of PD-1/PD-L1 expression is also less clear, antiPD1 antibody pembrolizumab was tested in a clinical trial and resulted in 38% objective response rate in heavily pretreated cutaneous pCTCL patients (36).…”