Encouraging First Study of Pembrolizumab in Cutaneous T-Cell Lymphoma

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Immunotherapy with an anti–programmed cell death protein 1 (PD-1) inhibitor—pembrolizumab (Keytruda)—showed encouraging responses in patients with advanced cutaneous T-cell lymphoma (either mycosis fungoides or Sézary syndrome). Pembrolizumab achieved a 38% overall response rate and responses appeared to be durable, according to the early results of a phase II trial reported at the 3rd World Congress of Cutaneous Lymphomas,1 sponsored by the International Society for Cutaneous Lymphomas.

Even the partial responses tend to be dramatic. Several patients had skin clearance by more than 90%, and the follow-up is still fairly short.
— Michael Khodadoust, MD, PhD

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“Until now, pembrolizumab has not been studied exclusively in cutaneous T-cell lymphoma. We were excited to do this trial confined to patients with this disease. The results were very encouraging, and we are waiting to see how durable the responses will be,” said Michael Khodadoust, MD, PhD, Instructor at Stanford University School of Medicine, Palo Alto, California.

“There is an unmet need for immunotherapies in cutaneous T-cell lymphoma. We need therapies that not only have a more reliable chance of response, but especially ones where the responses can last. Typically, the median duration of response is 6 to 8 months for most approved agents. Pembrolizumab is an attempt to unleash the antitumor T-cell response, and we saw encouraging results with the 38% response rate. Very importantly, these responses were long-lasting in most patients,” said principal investigator of this trial, Youn Kim, MD, also of Stanford University School of Medicine.

“The Cancer Immunotherapy Trials Network should be credited for the success of our pembrolizumab trial and all of the trials the network is sponsoring. The Cancer Immunotherapy Trials Network provides a great collaborative network with the National Cancer Institute, industry, and academic institutions, with great core clinical trials and biobank infrastructure, and we plan to continue to work with them,” Dr. Kim said.

Pembrolizumab is an attempt to unleash the antitumor T-cell response, and we saw encouraging results with the 38% response rate. Very importantly, these responses were long-lasting in most patients.
— Youn Kim, MD

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Cutaneous T-cell lymphoma is characterized by chromosomal rearrangements involving the programmed cell death ligand 1 and 2 (PD-L1/PD-L2). Most of the treatments are used empirically, and response duration is typically a few months, he said.

Key Study Findings

The phase II trial was a multicenter trial coordinated centrally by the Cancer Immunotherapy Trials Network. A total of 24 patients with advanced, heavily pretreated mycosis fungoides or Sézary syndrome (stage 1B or higher) were treated with pembrolizumab at 2 mg/kg every 3 weeks for up to 2 years if they showed a benefit. Two-thirds of patients had received four or more prior therapies, and two-thirds of patients had stage IVA disease.

At the time of data cutoff, median follow-up was 40 weeks. Overall response rate was 38% (1 complete response and 8 partial responses). Eleven patients had stable disease, and four patients had progressive disease.

Median time to response was 11 weeks, median progression-free survival had not been reached, and median duration of response had not yet been reached. One-year progression-free survival was 69%. “Even the partial responses tend to be dramatic. Several patients had skin clearance by more than 90%,” Dr. Khodadoust said.

Immunotherapy for Mycosis Fungoides and Sézary Syndrome

  • A phase II study showed encouraging results with immunotherapy in heavily pretreated patients with relapsed or refractory cutaneous T-cell lymphoma (mycosis fungoides and Sézary syndrome).
  • Overall response rate was 38%, and responses appear to be durable.
  • Further studies will explore pembrolizumab in combination therapy in the hope of boosting response rates and the duration of response.

At 63 weeks, all responders continued to respond. Responses were independent of gender, diagnosis, stage, number of prior therapies, or skin flare.

Pembrolizumab had excellent tolerability. Two patients had a serious adverse event (one duodenitis, one pneumonitis). Eight patients experienced a skin flare, and all eight had Sezary syndrome and high PD-1 expression. Flare was not observed in patients with mycosis fungoides.

Extensive correlative studies are planned in the hope of identifying a biomarker.

Next, the Cancer Immunotherapy Trials Network plans to study the combination of pembrolizumab plus interferon-gamma, which potentiates the T helper cell 1 (TH1) response thought to be beneficial in this disease. “We think this combination will be synergistic. We hope to achieve an even higher response rate, but maintain the durability of responses,” Dr. Khodadoust concluded.

Additional Commentary

John T. O’Malley, MD, PhD

John T. O’Malley, MD, PhD

“Immunotherapy with anti–PD-1 or anti–PD-L1 agents is a very promising avenue of research in cutaneous T-cell lymphoma,” declared John T. O’Malley, MD, PhD, of Dana-Farber/Brigham and Women’s Cancer Center, Harvard Medical School, Boston. “There is no systemic therapy available that is effective for all patients with this disease. The hope is that pembrolizumab can improve response rates, and combining it with other therapies will be interesting to pursue,” he added. ■

Disclosure: Drs. Khodadoust, Kim, and O’Malley reported no potential conflicts of interest.


1. Khodadoust MS, Rook AH, Porcu P, et al: Pembrolizumab for treatment of relapsed/refractory mycosis fungoides and Sézary syndrome: Clinical efficacy in a CITN multicenter phase 2 study. 3rd World Congress of Cutaneous Lymphomas. Abstract O-10. Presented October 28, 2016.