San Diego, CA—The PD-1 inhibitor pembrolizumab (Keytruda) has good activity in patients with relapsed or refractory mycosis fungoides or Sézary syndrome, and the responses it produces are deep and durable, according to study results reported by Michael Khodadoust, MD, PhD, Medicine-Oncology, Division of Oncology, Stanford University School of Medicine, CA, at the 2016 American Society of Hematology meeting.
In this multicenter phase 2 clinical trial, 9 of 24 patients with advanced-stage mycosis fungoides or Sézary syndrome had an objective response to pembrolizumab, he reported.
Mycosis fungoides and Sézary syndrome are the 2 most common subtypes of cutaneous T-cell lymphoma (CTCL), and prognosis remains poor for patients with advanced disease. Despite several treatment options, responses are short-lived. Durable therapies are therefore an unmet need, said Dr Khodadoust.
“In these diseases, the tumor cells are T-cells,” he said. “The most important implication of this is that the tumor cells also express PD-1; actually they highly express PD-1. So when we use therapies that are directed against PD-1, which are typical, we think of directing against the host immune response, we’re actually also hitting the malignant cells.”
In addition, in these lymphoma subtypes, PD-L1 can be expressed on the malignant cells themselves. Therefore, the PD-1/PD-L1 immune checkpoint axis is central to the biology of mycosis fungoides and Sézary syndrome.
The hypothesis for the single-arm study was that disrupting the PD-1/PD-L1 immune checkpoint with pembrolizumab would be an effective treatment strategy in CTCL. The study was coordinated by the Cancer Immunotherapy Trials Network and enrolled 24 patients with stage IB-IVB mycosis fungoides or Sézary syndrome. Patients received pembrolizumab 2 mg/kg every 3 weeks for up to 2 years.
The majority (63%) of patients had stage IVA Sézary syndrome and were heavily pretreated; most patients received at least 4 previous lines of therapy. The median follow-up was 40 weeks.
The objective response rate was 38% (9 of 24 patients), and 8 of the 9 patients whose disease responded had ongoing responses at a median of 32 weeks.
“Our response rate was very encouraging, and although we only had 1 complete response…the partial responses were actually quite deep, and some of them look very close to complete responses as well. We saw these responses across all clinical characteristics; we saw them in patients with mycosis fungoides or Sézary syndrome, all stages of the disease, and we also saw them in patients who had been heavily pretreated. Perhaps even more encouraging was the duration of these responses,” said Dr Khodadoust.
The time to response was a median of 11 weeks. The 1-year progression-free survival (PFS) was 69%, and the median PFS was not reached.
The safety profile was consistent with that seen in previous clinical trials of pembrolizumab, including 2 patients who had immune-mediated serious adverse events.
Additional correlative studies, including systemic immune profiling and molecular profiling, are planned to identify potential predictive biomarkers of response. A follow-up phase 2 clinical trial of pembrolizumab in combination with interferon-gamma in patients with CTCL is being developed based on these results, Dr Khodadoust concluded.