Pembrolizumab in relapsed and refractory mycosis fungoides and Sézary syndrome: A multicenter phase II study Journal Article
| Authors: | Khodadoust, M. S.; Rook, A. H.; Porcu, P.; Foss, F.; Moskowitz, A. J.; Shustov, A.; Shanbhag, S.; Sokol, L.; Fling, S. P.; Ramchurren, N.; Pierce, R.; Davis, A.; Shine, R.; Li, S.; Fong, S.; Kim, J.; Yang, Y.; Blumenschein, W. M.; Yearley, J. H.; Das, B.; Patidar, R.; Datta, V.; Cantu, E.; McCutcheon, J. N.; Karlovich, C.; Williams, P. M.; Subrahmanyam, P. B.; Maecker, H. T.; Horwitz, S. M.; Sharon, E.; Kohrt, H. E.; Cheever, M. A.; Kim, Y. H. |
| Article Title: | 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-g gene expression signature. CONCLUSION Pembrolizumab demonstrated significant antitumor activity with durable responses and a favorable safety profile in patients with advanced MF/SS. © 2019 by American Society of Clinical Oncology |
| Keywords: | adult; cancer survival; clinical article; treatment response; aged; gene mutation; overall survival; cancer recurrence; advanced cancer; drug efficacy; drug withdrawal; hypertension; side effect; systemic therapy; treatment duration; conference paper; cancer patient; follow up; cd3 antigen; cd8 antigen; transcription factor foxp3; cancer immunotherapy; progression free survival; phase 2 clinical trial; gene expression; anemia; tumor volume; pneumocystis pneumonia; alanine aminotransferase blood level; arthralgia; aspartate aminotransferase blood level; fever; pneumonia; pruritus; rash; alanine aminotransferase; aspartate aminotransferase; hypotension; gamma interferon; multicenter study; arthritis; peripheral edema; erythema; recurrent disease; colitis; corticosteroid; periorbital edema; disease exacerbation; mycosis fungoides; hypocalcemia; cd163 antigen; programmed death 1 ligand 1; programmed death 1 receptor; molecular pathology; sezary syndrome; clinical outcome; lung edema; corticosteroid therapy; cornea ulcer; human; male; female; priority journal; pembrolizumab; programmed death 1 ligand 2; whole exome sequencing; disease severity assessment; duodenitis; treatment response time; modified severity weighted assessment tool; refractory mycosis fungoides; refractory sezary syndrome |
| Journal Title: | Journal of Clinical Oncology |
| Volume: | 38 |
| Issue: | 1 |
| ISSN: | 0732-183X |
| Publisher: | American Society of Clinical Oncology |
| Date Published: | 2020-01-01 |
| Start Page: | 20 |
| End Page: | 28 |
| Language: | English |
| DOI: | 10.1200/jco.19.01056 |
| PUBMED: | 31532724 |
| PROVIDER: | scopus |
| PMCID: | PMC6943974 |
| DOI/URL: | |
| Notes: | Source: Scopus |
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