Immune-related adverse events correlate with improved survival in patients undergoing anti-PD1 immunotherapy for metastatic melanoma

Indini, Alice; Guardo, Lorenza Di; Cimminiello, Carolina; Prisciandaro, Michele; Randon, Giovanni; Braud, Filippo de; Vecchio, Michele Del

doi:10.1007/s00432-018-2819-x

Cited by 163 publications

(141 citation statements)

References 31 publications

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“…The current study results indicated a clinical correlation between the development of irAE and the efficacy of nivolumab monotherapy for MM. Furthermore, several studies reported that the development of vitiligo was specifically associated with improved survival in patients with advanced melanoma treated with anti‐PD‐1 monotherapy . These studies have suggested that host immune activation and antigens shared between the melanoma cells and the normal melanocytes may contribute to the association of vitiligo with better outcomes in these patients .…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, several studies reported that the development of vitiligo was specifically associated with improved survival in patients with advanced melanoma treated with anti-PD-1 monotherapy. 20,[33][34][35][36] These studies have suggested that host immune activation and antigens shared between the melanoma cells and the normal melanocytes may contribute to the association of vitiligo with better outcomes in these patients. 34,35 In our current study, the development of vitiligo was not associated with the efficacy of nivolumab monotherapy for MM, possibly because of the small sample size and number of patients with vitiligo.…”

Section: Discussionmentioning

confidence: 99%

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Immune‐related adverse events correlate with improved survival in patients with advanced mucosal melanoma treated with nivolumab: A single‐center retrospective study in Japan

Otsuka

Sugihara

Mori

et al. 2020

The Journal of Dermatology

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Immune‐related adverse events (irAE) were reported to be associated with better outcomes in various cancers treated with the immune checkpoint inhibitor nivolumab. Considering that their development depends on host immune activation, irAE may reflect antitumor response in mucosal melanoma (MM). This single‐center retrospective study including patients with advanced MM receiving nivolumab monotherapy between August 2014 and September 2018 investigated whether the development of irAE was associated with clinical efficacy. The study patients were divided into those with and without irAE, and treatment efficacy and safety were evaluated. The study cohort of 27 patients included 20 (74%), six (22%) and one (4%) patient with primary MM in the head and neck, genitourinary and anorectal regions, respectively. The irAE onset was not significantly associated with the objective response rate in patients while it was significantly associated with the disease control rate. The median progression‐free survival in patients with and without irAE was 301 and 63 days, respectively. The median overall survival (OS) in patients with and without irAE was 723 and 199 days, respectively. According to the timing of irAE onset, the OS was better in seven patients who developed irAE after 180 days than in nine patients who developed irAE within 180 days. Although 16 patients (59%) experienced any grade irAE, including three (11%) with grade 3 or more irAE, there were no treatment‐related deaths. These results indicated that the development of irAE may correlate with improved survival in patients with MM treated with nivolumab monotherapy. Further studies are necessary to confirm these findings.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Immune‐related adverse events correlate with improved survival in patients with advanced mucosal melanoma treated with nivolumab: A single‐center retrospective study in Japan

Otsuka

Sugihara

Mori

et al. 2020

The Journal of Dermatology

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“…The data published on the linkage between irAEs and outcome in patients treated with pembrolizumab are still limited, however, several studies suggest similar results to those obtained from studies with nivolumab. The retrospective study conducted by Indini et al including patients with metastatic MM (n=173) treated with pembrolizumab or nivolumab found a higher DCR (p=0.029) and longer PFS and OS in patients with any irAE in the multivariate Cox regression analysis (HR=0.47, p=0.016; HR=0.39, p=0.007) (29). Analysis of prospectively collected data from patients with advanced MM treated with pembrolizumab (n=147) found a higher DCR in patients who developed any irAE (75.0 vs. 17.9%, p=0.02) and the best results were achieved in patients with higher grade irAEs, in whom a significantly longer PFS and OS were found compared to patients without irAEs (HR=0.54, p<0.001; HR=0.51, p<0.001) (30).…”

Section: Iraes and Outcome In MMmentioning

confidence: 98%

Immune-related Adverse Effects and Outcome of Patients With Cancer Treated With Immune Checkpoint Inhibitors

et al. 2020

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“…In patients with melanoma, 1-year OS and PFS were 49% [95%, CI 40-58] and 26% [18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34], respectively (Supplementary Table 1). Median OS and PFS were 11.6 (iqr 3.4-29.6) and 3.9 (2.2-12.6) months, respectively.…”

Section: Efficacymentioning

confidence: 99%

“…The ORR was 33.9%. In patients with NSCLC, the 1-year OS and PFS were 44% [37-51] and 21% [16][17][18][19][20][21][22][23][24][25][26][27], respectively. Median OS and PFS were 9.1 (3.6-28.9) and 2.8 (1.6-10.4) months respectively.…”

Section: Efficacymentioning

confidence: 99%

The prognostic impact of immune-related adverse events during anti-PD1 treatment in melanoma and non–small-cell lung cancer: a real-life retrospective study

et al. 2019

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Background: Nivolumab and pembrolizumab, two PD1 inhibitors, trigger immune-related adverse events in approximately 50% of patients. Our objective was to determine whether these immunerelated adverse events are associated with patient outcomes. Patients and Methods: Retrospective cohort study, realized at the Institut Universitaire du Cancer de Toulouse, of all the patients treated with nivolumab or pembrolizumab off clinical trials. We included patients (i) diagnosed with unresectable stage III or stage IV melanoma or with recurrent stage IIIB or stage IV non-small cell lung cancer (ii) on nivolumab 3mg/kg or pembrolizumab 2mg/kg every 2 or 3 weeks respectively. Results: Of the 311 patients included (of 641 eligible subjects), 120 (38.6%) had melanoma and 191 (61.4%) had non-small cell lung cancer; 241 (77.5%) were treated with nivolumab with a median followup of 24 months (20-29). We observed 166 immune-related adverse events in 116 (37.3%) patients, categorized as "early" (onset before 12 weeks in melanoma and before 8 weeks in lung cancer) in 63 (54.3%) patients. Early and late adverse events were significantly associated with an increase in overall survival: adjusted hazard ratio 0.58 [0.41-0.84] (p = .003) and 0.28 [0.16-0.50] (p < .001) respectively. The overall response rate was significantly increased in patients with an immune-related adverse event (53.9% vs 12.9%, p < .001) Conclusions: This study validates the association between immune-related adverse events and anti-PD1 efficacy in real-life, especially if these events are delayed. Our results, along with further studies on the place of immunosuppressive drugs in the therapeutic strategy, could improve the management of these adverse events.

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Immune-related adverse events correlate with improved survival in patients undergoing anti-PD1 immunotherapy for metastatic melanoma

Cited by 163 publications

References 31 publications

Immune‐related adverse events correlate with improved survival in patients with advanced mucosal melanoma treated with nivolumab: A single‐center retrospective study in Japan

Immune‐related adverse events correlate with improved survival in patients with advanced mucosal melanoma treated with nivolumab: A single‐center retrospective study in Japan

Immune-related Adverse Effects and Outcome of Patients With Cancer Treated With Immune Checkpoint Inhibitors

The prognostic impact of immune-related adverse events during anti-PD1 treatment in melanoma and non–small-cell lung cancer: a real-life retrospective study

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