In a phase II study reported in the Journal of Clinical Oncology, Khodadoust et al found that pembrolizumab was active in patients with advanced relapsed or refractory mycosis fungoides or Sézary syndrome.

In the U.S.-based multicenter trial, 24 patients with advanced mycosis fungoides (n = 9) or Sézary syndrome (n = 15) were treated with pembrolizumab at 2 mg/kg every 3 weeks for up to 24 months. The primary endpoint was overall response rate by consensus global response criteria. In total, 23 of 24 patients had stage IIB to IV disease, and patients had received a median of four prior systemic therapies.

Responses

The overall response rate was 38%, with complete response reported in two patients and partial response in seven. Response was observed in five patients with mycosis fungoides (56%) and four with Sézary syndrome (27%). Response rates were similar among patients with four or more vs less than four prior therapies (33% vs 44%, P = .68).

Among the nine responders, six exhibited ≥ 90% improvement in skin disease on the modified Severity Weighted Assessment Tool, and eight had ongoing responses at last follow-up. The median duration of response was not reached over a median response follow-up time of 58 weeks. At 1 year, the progression-free survival rate was 65%, and overall survival was 95%.

Adverse Events

Treatment was discontinued in four patients (17%) due to immune-related adverse events, consisting of pneumonitis, duodenitis, aspartate transaminase/alanine transaminase increase, and corneal ulcer (all grade 3). No grade 4 immune-related adverse events were observed; the most common grade 3 events were cutaneous events, including rash and skin flare, which were observed in four patients (17%). Grade 4 Pneumocystis pneumonia was observed in one patient. and grade 3 anemia, hypotension, hypertension, pulmonary edema, and periorbital edema were each reported in one patient, respectively.

Transient worsening of erythroderma and pruritus occurred in eight patients (53%) with Sézary syndrome but did not result in discontinuation of treatment in any patient. This flare reaction was associated with high programmed cell death protein 1 expression on Sézary cells but was not associated with response or lack of response. Treatment response was not associated with programmed cell death ligand 1 expression, total mutation burden, or interferon-gamma gene-expression signature.

The investigators concluded: “Pembrolizumab demonstrated significant antitumor activity with durable responses and a favorable safety profile in patients with advanced mycosis fungoides or Sézary syndrome.”

Michael S. Khodadoust, MD, PhD, of Stanford University, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by Merck, National Cancer Institute grants, and the Haas Family Foundation. For full disclosures of the study authors, visit jco.ascopubs.org.