Abstract
Purpose
Although development of immune checkpoint inhibitors has revolutionized the treatment of metastatic melanoma, more than a half of treated patients experience disease progression during therapy. Cases of spontaneous vitiligo-like leukoderma have been described in melanoma patients and have been associated with a favorable outcome. This vitiligo-like leukoderma can also appear in melanoma patients undergoing immune therapies such as immune checkpoint inhibitors. However, no consensus exists about the relationship between vitiligo-like leukoderma onset and improved overall survival. Our study investigates the possible association between the onset of vitiligo-like leukoderma during immune checkpoint inhibitor treatment and a better prognosis.
Methods
A non-concurrent cohort study was conducted by identifying retrospectively 280 patients who had inoperable or metastatic melanoma and had undergone immune therapy with checkpoint inhibitors in any line of treatment. Toxicities developed during therapy were evaluated.
Results
Among the 280 study participants, 50% developed at least one type of toxicity, and vitiligo-like leukoderma was observed in 43 patients (15.4%). In the multivariate Cox model, a protective effect for mortality was observed for patients with vitiligo-like leukoderma development (HR : 0.23; 95% CI 0.11–0.44, p < 0.0001). In a sub-group analysis comprising only cutaneous melanoma in first line of treatment (N = 153), occurrence of vitiligo-like leukoderma was also an independent predictor factor for duration of clinical benefits measured by time to the next treatment (HR: 0.17; 95% CI 0.06–0.44).
Conclusion
Our findings indicate that onset of vitiligo-like leukoderma during melanoma treatment could be a marker of favorable outcome in patients treated with immune checkpoint inhibitors.
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Abbreviations
- MEK:
-
Mitogen-activated protein kinase
- ICI:
-
Immune checkpoint inhibitors
- CTLA-4:
-
Cytotoxic T-lymphocyte antigen-4
- PD-1:
-
Programmed cell death protein 1
- PFS:
-
Progression free survival
- OS:
-
Overall survival
- TMB:
-
Tumor mutational burden
- VLL:
-
Vitiligo-like leukoderma
- IL:
-
Interleukin
- irAE:
-
Immune-related adverse events
- LDH:
-
Lactate dehydrogenase
- TTNT:
-
Time-to-next treatment
- RECIST:
-
Response Evaluation Criteria in Solid Tumors
- CR:
-
Complete response
- PR:
-
Partial response
- SD:
-
Stable disease
- PD:
-
Progressive disease
- SD:
-
Standard deviation
- IQR:
-
Interquartile range
- HR :
-
Hazard ratio
- PD-L1:
-
PD-ligand-1
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Acknowledgements
This project was funded, in part, with grants from the “Progetto Ricerca Corrente”, RC20_4.1, of the Italian Ministry of Health. MLC is the recipient of a Young Investigator Fellowship from Fondazione Umberto Veronesi. Authors would like to acknowledge the efforts and care of the Oncology Department nurse team, and the contribution and compliance of the patients.
Funding
This project was funded, in part, with grants from the “Progetto Ricerca Corrente”, RC20_4.1, of the Italian Ministry of Health. MLC is the recipient of a Young Investigator Fellowship from Fondazione Umberto Veronesi.
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Conceptualization: SD, FDG, CMF, and CF; data collection and management: SV, FRDP, SM, MLC, RM, and FMM; formal analysis: SV, FRDP, SM, and MLC; methodology: SV, FRDP, SM, MLC, and CF; validation: SM, CF; writing original draft: SV, FRDP, MLC, CMF, and CF; writing review and editing: DA, RM, FMM, SD, PM, FDG, CMF, and CF; funding acquisition: CMF, CF, DA, FDG, and PM.
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Verkhovskaia, S., Di Pietro, F.R., Mastroeni, S. et al. Vitiligo-like leukoderma as an indicator of clinical response to immune checkpoint inhibitors in late-stage melanoma patients. J Cancer Res Clin Oncol 148, 2529–2538 (2022). https://doi.org/10.1007/s00432-021-03811-3
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DOI: https://doi.org/10.1007/s00432-021-03811-3