Ipilimumab/nivolumab/pembrolizumab

Ipilimumab/nivolumab/pembrolizumab Reactions 1680, p193 - 2 Dec 2017 Hyperprogression of melanoma with development of new metastases: case report A 49-year-old woman developed hyperprogression of melanoma and development of new metastases during treatment with ipilimimab, nivolumab and pembrolizumab [routes and outcomes not stated; not all dosages stated]. The woman was diagnosed with melanonoma with lung and axillary soft tissue metastases. She was started on a combination therapy with nivolumab and ipilimumab every three weeks. One month following the initiation of ipilimumab and nivolumab and completion of two cycles of the combination therapy, a CT scan was performed, which revealed an extremely rapid tumour progression. Furthermore, the tumour burden had increase by 246% with development of additional lung metastases. Fifty-seven days later after completion of three cycles of nivolumab and ipilimumab, follow-up CT scans were performed, which showed further disease progression with an increase in tumour burden of 377% as compared to the baseline tumour burden. Thereafter, a whole-exome and transcriptome sequencing was performed within the Molecularly Aided Stratification for Tumor Eradication Research molecular stratification registry study of the German Cancer Consortium. Simultaneously, she was started on pembrolizumab 2 mg/kg bodyweight. However, the disease progression was not curbed even after three cycles of pembrolizumab. Concurrently, she also developed multiple new metastases, which included extradural parietal tumour manifestations. Thereafter, the woman’s treatment was switched to carboplatin and paclitaxel polychemotherapy. The molecular analysis showed a rearranged genome with a focal amplification on 12q chromosome, including the MDM2 locus (7 copies) and with a highly amplified region on the 8q chromosome involving the proto-oncogene MYC (14 copies). MDM2 amplification was confirmed by chromogene in situ hybridisation of the biopsied formalin-fixed tumour tissue. The MDM2 amplification explained the unresponsiveness to immunotherapy. However, it was not definitively evident if the disease progression was accelerated as compared to the natural course of disease progression. It was a clinical observation that MDM family member amplifications could represent a resistant mechanism to immunotherapies. Author comment: "Genomics of immunotherapy- associated hyperprogressors". "CT scans of progredient soft tissue metastasis (top row) and lung metastasis (bottom row) document the rapid tumor progression after initiation of an [ipilimumab,nivolumab, pembrolizumab] immunotherapy". Forschner A, et al. Genomics of immunotherapy-associated hyperprogressors - Letter. Clinical cancer research: an official journal of the American Association for Cancer Research 23: 6374-6376, No. 20, 15 Oct 2017. Available from: URL: http:/ /doi.org/10.1158/1078-0432.CCR-17-1480 - Germany 803284983 0114-9954/17/1680-0001/$14.95 Adis © 2017 Springer International Publishing AG. All rights reserved Reactions 2 Dec 2017 No. 1680 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Reactions Weekly Springer Journals

Ipilimumab/nivolumab/pembrolizumab

Reactions Weekly , Volume 1680 (1) – Dec 2, 2017
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Publisher
Springer International Publishing
Copyright
Copyright © 2017 by Springer International Publishing AG, part of Springer Nature
Subject
Medicine & Public Health; Drug Safety and Pharmacovigilance; Pharmacology/Toxicology
ISSN
0114-9954
eISSN
1179-2051
D.O.I.
10.1007/s40278-017-39124-7
Publisher site
See Article on Publisher Site

Abstract

Reactions 1680, p193 - 2 Dec 2017 Hyperprogression of melanoma with development of new metastases: case report A 49-year-old woman developed hyperprogression of melanoma and development of new metastases during treatment with ipilimimab, nivolumab and pembrolizumab [routes and outcomes not stated; not all dosages stated]. The woman was diagnosed with melanonoma with lung and axillary soft tissue metastases. She was started on a combination therapy with nivolumab and ipilimumab every three weeks. One month following the initiation of ipilimumab and nivolumab and completion of two cycles of the combination therapy, a CT scan was performed, which revealed an extremely rapid tumour progression. Furthermore, the tumour burden had increase by 246% with development of additional lung metastases. Fifty-seven days later after completion of three cycles of nivolumab and ipilimumab, follow-up CT scans were performed, which showed further disease progression with an increase in tumour burden of 377% as compared to the baseline tumour burden. Thereafter, a whole-exome and transcriptome sequencing was performed within the Molecularly Aided Stratification for Tumor Eradication Research molecular stratification registry study of the German Cancer Consortium. Simultaneously, she was started on pembrolizumab 2 mg/kg bodyweight. However, the disease progression was not curbed even after three cycles of pembrolizumab. Concurrently, she also developed multiple new metastases, which included extradural parietal tumour manifestations. Thereafter, the woman’s treatment was switched to carboplatin and paclitaxel polychemotherapy. The molecular analysis showed a rearranged genome with a focal amplification on 12q chromosome, including the MDM2 locus (7 copies) and with a highly amplified region on the 8q chromosome involving the proto-oncogene MYC (14 copies). MDM2 amplification was confirmed by chromogene in situ hybridisation of the biopsied formalin-fixed tumour tissue. The MDM2 amplification explained the unresponsiveness to immunotherapy. However, it was not definitively evident if the disease progression was accelerated as compared to the natural course of disease progression. It was a clinical observation that MDM family member amplifications could represent a resistant mechanism to immunotherapies. Author comment: "Genomics of immunotherapy- associated hyperprogressors". "CT scans of progredient soft tissue metastasis (top row) and lung metastasis (bottom row) document the rapid tumor progression after initiation of an [ipilimumab,nivolumab, pembrolizumab] immunotherapy". Forschner A, et al. Genomics of immunotherapy-associated hyperprogressors - Letter. Clinical cancer research: an official journal of the American Association for Cancer Research 23: 6374-6376, No. 20, 15 Oct 2017. Available from: URL: http:/ /doi.org/10.1158/1078-0432.CCR-17-1480 - Germany 803284983 0114-9954/17/1680-0001/$14.95 Adis © 2017 Springer International Publishing AG. All rights reserved Reactions 2 Dec 2017 No. 1680

Journal

Reactions WeeklySpringer Journals

Published: Dec 2, 2017

References

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