Efficacy of Immunotherapy in Patients with Metastatic Mucosal or Uveal Melanoma

Mignard, C.; Huvier, Aurélie Deschamps; Gillibert, André; Modeste, A.-B. Duval; Dutriaux, Caroline; Khammari, Amir; Avril, Marie-Françoise; Kramkimel, N.; Mortier, Laurent; Marcant, Pierre; Lesimple, Thierry; Gaudy‐Marqueste, C.; Lesage, C.; Machet, L.; Aubin, F.; Meyer, Nicolas; Bénéton, N.; Jeudy, G.; Montaudié, Henri; Arnault, Jean‐Philippe; Visseaux, L.; Trabelsi, Saoussen; Amini‐Adlé, Mona; Maubec, E.; Corre, Y. Le; Lipsker, Dan; Wierzbicka-Hainaut, E.; Litrowski, N.; Stefan, A.; Brunet‐Possenti, F.; Leccia, Marie‐Thérèse; Joly, P.

doi:10.1155/2018/1908065

Cited by 59 publications

(52 citation statements)

References 34 publications

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“…Immune checkpoint inhibitors, such as ipilimumab, nivolumab, and pembrolizumab, achieve long-term OS with 5-year OS rates of 34–52% in metastatic cutaneous melanoma [ 7 – 9 ] but yield poor outcome results in metastatic uveal melanoma (UM) with a median OS of 10–14 months [ 10 – 13 ]. At present, there is no standard therapy for metastatic UM, and the limited activity of systemic therapy compared with cutaneous melanoma poses a treatment challenge.…”

Section: Introductionmentioning

confidence: 99%

Unresectable Hepatic Metastasis of Uveal Melanoma: Hepatic Chemosaturation with High-Dose Melphalan—Long-Term Overall Survival Negatively Correlates with Tumor Burden

Brüning

Tiede

Schneider

et al. 2020

Radiology Research and Practice

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Introduction. Percutaneous hepatic perfusion with melphalan (PHP-M) for hepatic metastasis of uveal melanoma (LMUM) achieves high local response rates, but the individual clinical benefit is poorly defined. We aimed to determine cofactors of response and clinical outcomes including the probability of long-term (5-years) overall survival (OS) in PHP-M-treated patients with LMUM. Patients and Methods. We retrospectively reviewed clinicopathological, radiological, and outcome data of 19 patients with unresectable LMUM treated with 43 PHP-M (median 2 PHP-M) between 2014 and 2019. Tumor response and adverse events were evaluated using RECIST 1.1 and the Clavien–Dindo classification. Kaplan–Meier methods and Cox regression hazard proportional models were used. Results. Of 19 patients, 10 (53%) achieved a partial response (PR) and 9 (47%) had stable disease (SD). There was no progressive disease (PD) and no adverse events exceeding Clavien–Dindo grade IV. Median OS was 16.7 months after the first PHP-M treatment and 26.4 months after initial diagnosis. Low hepatic tumor volume (median of 10 mL vs. 150 mL) was an independent predictor of favorable OS (hazard ratio (95% confidence interval): 0.190 (0.041, 0.893); p<0.05), and female patients were at a lower risk compared with males (0.146 (0.017, 1.240)). Estimates of the overall survival were 0.213 (0.0449, 1) from first imaging (95% confidence interval) to 5 years and 0.793 (0.609, 1) and 0.604 (0.380, 0.960) for 1 and 2 years after chemosaturation, respectively. Discussion. PHP-M for nonresectable LMUV provides a safe and locally efficient liver-directed procedure that offers patients a chance for long-term OS, especially for patients with a low hepatic tumor burden.

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Section: Introductionmentioning

confidence: 99%

Unresectable Hepatic Metastasis of Uveal Melanoma: Hepatic Chemosaturation with High-Dose Melphalan—Long-Term Overall Survival Negatively Correlates with Tumor Burden

Brüning

Tiede

Schneider

et al. 2020

Radiology Research and Practice

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“…In a French retrospective study [57], 210 patients with metastatic UM were treated with the anti-CTLA-4 antibody ipilimumab or the anti-PD-1 antibodies nivolumab or pembrolizumab. No partial or complete response of metastases was observed.…”

Section: Uveal Melanomamentioning

confidence: 99%

“…The OS of mucosal melanoma patients treated with CPIs appeared to be longer than that of patients treated with chemotherapy, with a median OS of 15.97 months and 8.82 months, respectively. In conclusion, immunotherapy appears to improve overall survival for patients with metastatic mucosal melanoma [57]. In a pooled analysis [63], the outcome of patients with metastatic mucosal melanoma treated in trials either with single-agent nivolumab (n = 86) or the combination of nivolumab and ipilimumab (n = 35) was reported.…”

Section: Mucosal Melanomamentioning

confidence: 99%

Anti-PD-1 and Novel Combinations in the Treatment of Melanoma—An Update

Gellrich

Schmitz

Beissert

et al. 2020

JCM

108

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Until recently, distant metastatic melanoma was considered refractory to systemic therapy. A better understanding of the interactions between tumors and the immune system and the mechanisms of regulation of T-cells led to the development of immune checkpoint inhibitors. This review summarizes the current novel data on the treatment of metastatic melanoma with anti-programmed cell death protein 1 (PD-1) antibodies and anti-PD-1-based combination regimens, including clinical trials presented at major conference meetings. Immune checkpoint inhibitors, in particular anti-PD-1 antibodies such as pembrolizumab and nivolumab and the combination of nivolumab with the anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibody ipilimumab can achieve long-term survival for patients with metastatic melanoma. The anti-PD-1 antibodies nivolumab and pembrolizumab were also approved for adjuvant treatment of patients with resected metastatic melanoma. Anti-PD-1 antibodies appear to be well tolerated, and toxicity is manageable. Nivolumab combined with ipilimumab achieves a 5 year survival rate of more than 50% but at a cost of high toxicity. Ongoing clinical trials investigate novel immunotherapy combinations and strategies (e.g., Talimogene laherparepvec (T-VEC), Bempegaldesleukin (BEMPEG), incorporation or sequencing of targeted therapy, incorporation or sequencing of radiotherapy), and focus on poor prognosis groups (e.g., high tumor burden/LDH levels, anti-PD-1 refractory melanoma, and brain metastases).

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“…The efficacy achieved in the management of metastatic cutaneous melanoma and other cancers with reported durable response rates ranging from 20 to over 60%, has not been observed in mUM [ 205 , 206 , 207 ]. Studies reported a response rate below 10%, and a median survival less of than 1 year with a single-agent checkpoint block have been widely described [ 208 , 209 , 210 , 211 , 212 , 213 ]. This is likely related to the immune privilege of the eye, which establishes mechanisms to evade the immune system, and with the low mutational load with limited potential neoepitopes of UM if compared with cutaneous melanoma.…”

Section: Treatment Of Metastatic Diseasementioning

confidence: 99%

Molecular Insights and Emerging Strategies for Treatment of Metastatic Uveal Melanoma

Mallone

Sacchetti

Moramarco

2020

Cancers

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Uveal melanoma (UM) is the most common intraocular cancer. In recent decades, major advances have been achieved in the diagnosis and prognosis of UM allowing for tailored treatments. However, nearly 50% of patients still develop metastatic disease with survival rates of less than 1 year. There is currently no standard of adjuvant and metastatic treatment in UM, and available therapies are ineffective resulting from cutaneous melanoma protocols. Advances and novel treatment options including liver-directed therapies, immunotherapy, and targeted-therapy have been investigated in UM-dedicated clinical trials on single compounds or combinational therapies, with promising results. Therapies aimed at prolonging or targeting metastatic tumor dormancy provided encouraging results in other cancers, and need to be explored in UM. In this review, the latest progress in the diagnosis, prognosis, and treatment of UM in adjuvant and metastatic settings are discussed. In addition, novel insights into tumor genetics, biology and immunology, and the mechanisms underlying metastatic dormancy are discussed. As evident from the numerous studies discussed in this review, the increasing knowledge of this disease and the promising results from testing of novel individualized therapies could offer future perspectives for translating in clinical use.

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Efficacy of Immunotherapy in Patients with Metastatic Mucosal or Uveal Melanoma

Cited by 59 publications

References 34 publications

Unresectable Hepatic Metastasis of Uveal Melanoma: Hepatic Chemosaturation with High-Dose Melphalan—Long-Term Overall Survival Negatively Correlates with Tumor Burden

Unresectable Hepatic Metastasis of Uveal Melanoma: Hepatic Chemosaturation with High-Dose Melphalan—Long-Term Overall Survival Negatively Correlates with Tumor Burden

Anti-PD-1 and Novel Combinations in the Treatment of Melanoma—An Update

Molecular Insights and Emerging Strategies for Treatment of Metastatic Uveal Melanoma

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