Pembrolizumab Effectively Treats Relapsed/Refractory CTCLs


Pembrolizumab has good activity, is safe and well-tolerated, and induces durable responses in cutaneous T-cell lymphomas, according to a study presented at the American Society of Hematology Annual Meeting & Exposition.

SAN DIEGO-Pembrolizumab has good activity, is safe and well-tolerated, and induces durable responses in cutaneous T-cell lymphomas (CTCLs), according to a study presented (abstract 181) at the American Society of Hematology Annual Meeting & Exposition, held December 3–6, 2016.

Prognosis remains poor for advanced stage CTCLs, including mycosis fungoides (MF) and Sézary syndrome (SS). Several treatment options are available, but responses are short-lived, said lead author Michael Khodadoust, MD, an oncologist at Stanford University School of Medicine, Stanford, Calif. “In these diseases, the tumor cells are T cells. This has an important implication because the tumor cells highly express programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1),” he said.

Khodadoust and colleagues tested whether disruption of PD-1/PD-L1 with the immune checkpoint inhibitor pembrolizumab would be an effective treatment strategy in CTCL. They conducted a single-arm, phase II study of 24 patients with MF/SS stages IB-IV treated with at least one prior systemic therapy.

Pembrolizumab was administered at 2 mg/kg every 3 weeks and treatment was allowed up to 2 years. The primary endpoint was overall response rate (ORR).

All 24 patients, median age 67 years, received at least one dose of pembrolizumab. Most patients were heavily pretreated, with a median of four prior systemic therapies. The median follow-up time was 40 weeks.

The results show the ORR was 38% with one complete response and eight partial responses. Six of the nine responding patients had 90% or greater improvement in skin disease. An additional nine patients had stable disease. The median time to response was 11 weeks.

“Most encouraging was the duration of response,” said Khodadoust. “Responses tended to deepen throughout treatment.” Eight of the nine (89%) responders are currently continuing treatment at a median of 32 weeks.

The median progression-free survival (PFS) has not yet been reached, and the 1-year PFS was 69%.

There was no significant association between response and clinical characteristics, including stage, disease type (MF vs SS), and number of prior therapies, or with skin tissue expression of PD-1, PD-L1, PD-L2, or infiltrating CD8+ T cells as determined by immunohistochemistry.

Adverse events were consistent with those seen in prior studies of pembrolizumab, with the exception of a unique immune-mediated skin flare reaction seen in six patients (two grade 2 and four grade 3). Skin flares occurred exclusively in patients with SS and appeared as early as the first cycle of treatment, he said, adding that high-dimension analysis has determined that high PD-1 expression may predict skin flare reactions.

Additional planned correlative studies, including systemic immune profiling and molecular profiling, will explore other potential predictive biomarkers of response.

There were two treatment-related serious adverse events, both immune related. One patient experienced grade 2 pneumonitis, which resolved with systemic corticosteroids. Another patient experienced grade 3 diarrhea secondary to steroid-refractory duodenitis. 

A phase II trial in CTCL patients of pembrolizumab in combination with interferon-gamma is being developed based on these results.


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