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Survival advantage suggested in responders to immunotherapy for uveal melanoma
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A possible survival advantage in patients with metastatic uveal melanoma who respond to treatment with pembrolizumab is suggested in a study of the anti-PD-1 monoclonal antibody as immunotherapy for advanced disease.
Researchers enrolled 17 patients with metastatic uveal melanoma in a prospective observational cohort single-arm study to investigate efficacy and safety of pembrolizumab as a first line-therapy. Endpoints were progression-free survival, complete or partial response or disease stabilization, clinical benefit, overall survival and tolerability.
A median of eight cycles of intravenous 2 mg/kg pembrolizumab every 3 weeks was administered. Range of administration cycles was two to 28, until disease progression, toxicity or withdrawal of consent. Toxicity was reported to be mild.
Two patients achieved a partial response and were without progression after 19.4 and 28.9 months (response rate, 11.7%). Both patients were still on treatment at the time of data analysis. Disease stabilized in six patients and progressed in nine. Eight of the 17 patients (47%) were deemed to have achieved clinical benefit.
Progression-free survival was 3.8 months for all patients, 9.7 months for patients whose interval between diagnosis of primary tumor to metastatic disease was longer than 5 years, and 2.6 months for patients whose same interval was less than 5 years.
“Based on our data, relapse after 5 years from the diagnosis of primary tumor could be considered a parameter to select patients who may benefit more from immunotherapy,” the authors said. “[T]he identification of predictive factors for response is crucial.” – by Robert Linnehan
Disclosures: The authors report no relevant financial disclosures.
Perspective
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Carol L. Shields, MD
The management of metastatic uveal melanoma is challenging, and results following chemotherapy trials have been discouraging. There is interest in immunotherapy, and particularly systemic checkpoint inhibitors, for better control of this potentially fatal disease. Checkpoint inhibitors work at the level of the T cell, blocking built-in controls and unleashing T cells to activity. Pembrolizumab is one of several checkpoint inhibitors and specifically functions as an anti-PD-1 monoclonal antibody.
Previous studies on checkpoint inhibitors for metastatic uveal melanoma have been unimpressive. Algazi and colleagues reported results from a nine-center collaboration of 56 patients who received PD-1 or PD-L1 antibodies, 48 (86%) of which had prior therapy and only 3.6% demonstrated tumor response. These authors speculated that the low response of uveal melanoma was that it was inherently less antigenic for attraction of T cells due to its low somatic mutational burden.
In this analysis, pembrolizumab was used to treat metastatic uveal melanoma as first-line therapy in 17 patients. The authors found a response rate of 11.7%, which is lower than that of cutaneous melanoma (30% to 40%), but slightly higher than previous study on uveal melanoma (3.7%). Of the two responders, both survived with tumor control for at least 19 months. The authors studied potential factors that could identify responders from nonresponders and specifically noted no predictive factor, including expression of PD-L1 or genetic results (chromosomes three and eight).
These findings are important and a bit promising. Understanding uveal melanoma and its immune biology needs further study to better target this tumor with immunotherapy. Perhaps “inflaming” the tumor with various immunotherapeutic, chemotherapeutic or radiotherapeutic methods could promote a more robust immune response.
References:
Algazi AP, et al. Cancer. 2016;doi:10.1002/cncr.30258.
Dalvin LA, et al. Retina. 2018;doi:10.1097/IAE.0000000000002181.
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