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Exploratory analysis of clinical benefit of ipilimumab and nivolumab treatment in patients with metastatic melanoma from a single institution

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Abstract

Purpose

We retrospectively analysed overall survival (OS) and potential predictive biomarkers of OS in patients with metastatic melanoma treated with ipilimumab plus nivolumab in a single institution.

Methods and patients

Electronic medical records of patients with advanced melanoma receiving ≥ 1 dose of a combined ipilimumab plus nivolumab regimen between March 3, 2016 and March 7, 2020 in a single institution, were reviewed. OS was analysed using the Kaplan–Meier method. Sub-group analyses were conducted to examine several endpoints according to relevant clinical, molecular and pathological variables using logistic and Cox models.

Results

Forty-four cases were reviewed, 38 (86.4%), of whom had cutaneous melanoma, 21 (47.7%) were BRAF mutant, 21 (47.7%) presented high lactate dehydrogenase (LDH) values, 23 (52.3%) had ≥ 3 disease sites, and 10 (22.7%) patients had brain metastases. The median follow-up was 37.7 months, and the median OS was 21.1 months (95% CI 8.2–NR). In the multivariate analysis, the OS was significantly longer in patients with an Eastern Cooperative Oncology Group (ECOG) score of 0, LDH ≤ upper limit of normal, absence of liver metastases and neutrophil-to-lymphocyte ratio (NLR) < 5 (all p ≤ 0.05, log-rank test). These factors allowed the classification of patients into three prognostic risk groups (low/intermediate/high risk) for death.

Conclusion

Overall survival of real-world patients from our cohort receiving ipilimumab plus nivolumab was lower than in previous studies. The ECOG score, LDH values, the presence of liver metastases and the NLR were independent prognostic factors for survival.

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Author information

Authors and Affiliations

  1. Department of Medical Oncology, Hospital Clinic, Barcelona, Spain

    C. M. Vila, F. A. Moreno, G. R. Ares, P. Dashti, H. S. Oberoi, R. Martin-Huertas & A. A. Fernandez

  2. Department of Medical Oncology, Althaia Xarxa Assistencial Universitària de Manresa, Manresa, Spain

    C. M. Vila

  3. Programa de Doctorat en Medicina i Recerca Translacional, Facultat de Medicina, Universitat de Barcelona, Barcelona, Spain

    C. M. Vila

  4. Department of Oncology, Galdakao Hospital, Galdakao, Galdakao, Spain

    M. M. Estébanez

  5. Supportive Palliative Care Unit, University Hospital Principe de Asturias, Madrid, Spain

    G. R. Ares

  6. Oncology Data Science, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain

    G. Villacampa

  7. Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN, USA

    P. Dashti

  8. Department of Medical Oncology, Vall D’Hebron University Hospital, Barcelona, Spain

    H. S. Oberoi

  9. Department of Pathology, Hospital Clinic, Barcelona, Spain

    P. Jares, L. Alos & C. Teixido

  10. Department of General Surgery, Hospital Clinic, Barcelona, Spain

    R. Rull

  11. Department of Radiology, Hospital Clinic, Barcelona, Spain

    M. Sanchez

  12. Department of Dermatology, Hospital Clinic, Barcelona, Spain

    J. Malvehy

  13. Department of Pharmacy, Hospital Clinic, Barcelona, Spain

    E. Carcelero

  14. Department of Radiotherapy, Hospital Clinic, Barcelona, Spain

    I. Valduvieco

  15. Translational Genomics and Targeted Therapies in Solid Tumors, IDIBAPS, Barcelona, Spain

    F. A. Moreno, P. Jares, L. Alos, C. Teixido & A. A. Fernandez

  16. Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Barcelona, Spain

    F. A. Moreno

  17. Universitat Pompeu Fabra, Barcelona, Spain

    F. A. Moreno

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  1. C. M. Vila
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Corresponding author

Correspondence to C. M. Vila.

Ethics declarations

Ethics approval and consent to participate

All patients signed a informed consent ant the protocol was approved by local Ethical's Comittee.

Consent for publication

All patients gave consent for publication.

Availability of data and material

Electronic medical records from our centre.

Competing interests

Martínez Vila C. and Aya Moreno F have received travel grants and other honoraria from BMS, MSD, Novartis and Roche. Teixido C., has received personal fees from Pfizer, Novartis, MSD, Roche, AstraZeneca and Takeda, and research funding from Novartis. Arance Fernandez A.M. discloses travel grants, speaking fees and paid consulting from BMS, Roche, Novartis, Pierre-Fabre, Merck Serono, Sanofi and MSD. None were declared for the remaining authors.

Funding

Aya Moreno F, is a recipient of a PhD for Medical Doctors Program Fellowship and a grant from the Spanish Multidisciplinary Melanoma Group (GEM). Malvehy J., grants to his institution from Leo Pharma, Almirall, Castle Bioscience, AMLO Bioscience, Melagenics, Amgen, Roche-Posay ; Consultancy fees from Almirall, Amgen, Leo Pharma, Isdin, Sunpharma, Roche, Pierre Fabre; Speaker bureau from La Roche Posay, Roche, Pierre Fabre, BMS, Bioderma, Sanofi, ISDIN, Sunpharma.

Authors’ contributions

Manuscript writing: Martínez Vila C., Arance Fernandez A.M. Manuscript editing: Martinez Vila, C., Aya Moreno F., Mugica Estébanez M., Ruiz G., Villacampa G., Dashti P., Oberoi H. S., Martin-Huertas R., Jares P., Alos L., Teixido C., Rull R., Sanchez M., Malvehy J., Carcelero E., Valduvieco I., Arance Fernandez A.. Collecting data: Martinez Vila, C., Aya Moreno F., Mugica Estébanez M., Ruiz G., Villacampa G., Dashti P., Oberoi H. S., Martin-Huertas R., Jares P., Alos L., Teixido C., Rull R., Sanchez M., Malvehy J., Carcelero E., Valduvieco I., Arance Fernandez A.

Acknowledgements

To the patients and their families.

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Appendix

Appendix

See Table 4 and Fig. 

Fig. 4
figure 4

Mutation and wild-type landscape with targeted DNA-based NGS

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Vila, C.M., Moreno, F.A., Estébanez, M.M. et al. Exploratory analysis of clinical benefit of ipilimumab and nivolumab treatment in patients with metastatic melanoma from a single institution. Clin Transl Oncol 24, 319–330 (2022). https://doi.org/10.1007/s12094-021-02692-9

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