Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 14-Day Trial for You or Your Team.

Learn More →

Safe Administration of Ipilimumab, Pembrolizumab, and Nivolumab in a Patient with Metastatic Melanoma, Psoriasis, and a Previous Guillain–Barré Syndrome

Safe Administration of Ipilimumab, Pembrolizumab, and Nivolumab in a Patient with Metastatic... Hindawi Case Reports in Oncological Medicine Volume 2018, Article ID 2783917, 4 pages https://doi.org/10.1155/2018/2783917 Case Report Safe Administration of Ipilimumab, Pembrolizumab, and Nivolumab in a Patient with Metastatic Melanoma, Psoriasis, and a Previous Guillain–Barre´ Syndrome 1,2 1,2 2,3 2 Alessio Cortellini , Alessandro Parisi, Maria Concetta Fargnoli, Katia Cannita, 1,2 1,2 4 1,2 Azzurra Irelli , Giampiero Porzio, Claudio Martinazzo, and Corrado Ficorella Medical Oncology Unit, St. Salvatore Hospital, L’Aquila, Italy Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila, L’Aquila, Italy Oncological Dermatology Unit, St. Salvatore Hospital, L’Aquila, Italy Department of Neurophysiopathology, St. Salvatore Hospital, L’Aquila, Italy Correspondence should be addressed to Alessio Cortellini; alessiocortellini@gmail.com Received 21 October 2017; Accepted 10 January 2018; Published 8 March 2018 Academic Editor: Jose I. Mayordomo Copyright © 2018 Alessio Cortellini et al. &is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background. Patients with autoimmune diseases were not evaluated in clinical trials with immune checkpoint inhibitors (ICIs), since a history of immune disorders, such as Guillain–Barre syndrome (GBS) and psoriasis, is one of the major risk factors for the development of immune-related adverse events (irAEs). &is risk cannot be defined; therefore, physicians are called to manage these patients in clinical practice. Case Report. We report the case of a 62-year-old male patient affected by metastatic melanoma, with a history of GBS and psoriasis, and treated with sequential ipilimumab, pembrolizumab, and nivolumab, without significant toxicities. Conclusion. &is case report supports that although a history of immune disorders is one of the major risk factors for development of irAEs, in some patients, it could be possible to safely administer sequential treatments with ICIs. A proper decision should be made, considering therapeutic options, disease-related risks, and those related to a recurrence of preexisting autoimmune disorders. more frequently related to ipilimumab than to nivolumab or 1. Introduction pembrolizumab; they are rare, occurring approximately in Before starting a treatment with immune checkpoint in- 1% of patients and up to 4.5% when referring to all neu- hibitors (ICIs), oncologists must identify potential risk fac- rological toxicities [2–5]. Guillain–Barre syndrome (GBS) is tors, such as previous or concomitant dysimmune disorders, an acute polyradiculoneuropathy with variable clinical presentation. &e pathogenesis of GBS is unclear, but it is that could favour the development of immune-related adverse events (irAEs). Unfortunately, patients with a history of well known that it is caused by cellular and humoral immune autoimmune diseases were not included in clinical trials; self-response against peripheral nerves. GBS could be however, after careful baseline assessment, they are more considered as an exceptional irAE with only five cases re- frequent than expected in common clinical practice. In this ported [6–10]. Numerous triggering events have been de- case, proper management, early diagnosis, and careful pre- scribed, such as infections; GBS can lead to death as a result and post-treatment monitoring of irAEs are required [1]. of complications (infections, thromboembolic events, re- IrAEs are reported more frequently with anti-CTLA4 (cyto- spiratory failure, and cardiac arrhythmias) in about 5% of toxic T-lymphocyte-associated antigen 4) monotherapy rather cases [11]. Skin disorders are the most frequent toxicity of than with anti-PD-1/PD-L1 (programmed death-1/programmed ICIs: overall incidence of dermatological irAEs appeared to be death-ligand 1) [2]. Immune-mediated polyneuropathies are similar with anti-CTLA4 and anti-PD-1/PD-L1. Considering 2 Case Reports in Oncological Medicine any grade, they occur from 10% to 60% (in combination resulting in 23 out of 42 metastatic lymph nodes; PETscan in therapy) of patients [3–5, 12–15]. Most cutaneous irAEs are December 2015 still demonstrated residual disease in the mild, reversible, and easily manageable following guidelines; retroperitoneal lymph nodes. He came to our attention at the they are often T-cell-mediated even if the pathophysiology is age of 62, in quite good clinical conditions, with eastern still unknown. Psoriasis is a multifactorial immune-mediated cooperative oncology group performance status (ECOG-PS) chronic cutaneous disease, characterized by a wide range of 1. &e BRAF mutational analysis (V600) was negative clinical manifestations from mild to severe forms. Worsening (cobas z 480 analyzer). &e high tumor burden, with LDH and recurrence of psoriasis have been reported during the use more than 2 ULN, and the absence of an actionable BRAF of ICIs, with both anti-CTLA4 and anti-PD-1, such as niv- mutation led us to choose a first-line treatment with immune olumab [16–20]. Recently, a case series of advanced melanoma checkpoint inhibitors (ICIs). At that time, the only “in-label” patients treated with anti-PD-1 therapy and with preexisting drug in Italy for first-line treatment of BRAF wild-type autoimmune disorders has included 2 patients with a history advanced melanoma patients was ipilimumab (Yervoy ; of GBS (none of them experienced a worsening/flare) and Bristol-Myers Squibb Pharma EEIG, Uxbridge, United 6 patients with a history of psoriasis (3 of them experienced Kingdom). Before starting ipilimumab, we made a careful cutaneous irAEs) [21]. We report the case of a 62-year-old multidisciplinary assessment with dermatological and neu- male patient, with metastatic melanoma and a history of GBS rological evaluation. On dermatological evaluation, the pa- and psoriasis. &e patient was treated with sequential tient presented psoriatic plaques on the trunk and extremities; ipilimumab, pembrolizumab, and nivolumab, without sig- a baseline EMG was performed that showed the residual nificant toxicities or worsening of the preexisting autoimmune functional loss, mainly to the legs (Figure 1). disorders. &e patient was treated in clinical practice with “in- From December 11, 2015, to February 19, 2016, 4 induction label” drugs in Italy and provided written informed consent to doses of ipilimumab (3 mg/kg every three weeks) were ad- the proposed treatment; procedures followed in reporting the ministered without significant toxicities, except development case are in accordance with the ethical standard of the local of cutaneous facial vitiligo on the face; psoriatic plaques responsible committee on human experimentation. remained unchanged, and the patient did not develop new neurological symptoms. A CT scan in March 2016 showed an immune-related response of disease (dimensional reduction 2. Case Presentation and intralesional necrosis) and also detected a pulmonary We report the case of a male patient, a smoker, with a history embolism, treated with low molecular weight heparin. In of chronic obstructive lung disease, atrial fibrillation, hy- April 2016, the CT scan showed resolution of pulmonary pertension, obesity, chronic plaque psoriasis, and Guillain– embolism, and neurological evaluation showed no changes, Barre´ syndrome (GBS). &e diagnosis of GBS dated back to just like the control EMG that was performed. 2002; during a community-acquired pneumonia, a molecular In June 2016, the CT scan showed progressive disease to mimetism between bacterial antigens and gangliosides of the the lymph nodes; therefore, the patient underwent a second- nerves’ myelin sheath led to the development of a severe and line therapy with pembrolizumab (2 mg/kg every three rapidly progressive muscle weakness with areflexia, till tet- weeks) (Keytruda ; Merck Sharp & Dohme Limited, Hoddesdon, raplegia. Electromyography (EMG) confirmed acute, axonal United Kingdom), with only one dose administered, on July 11. polyneuropathy, with reduced sensory action potential, After that, he decided to continue the treatment at an outpatient supporting the diagnosis of the “acute motor and sensory cancer care center closer to his home. From October to axonal neuropathy” (AMSAN) type of GBS. &e patient was November 2016, he received 3 doses of nivolumab (3 mg/kg hospitalized and successfully treated with intravenous im- every two weeks) (Opdivo ; Bristol-Myers Squibb Pharma munoglobulins; he then underwent upper left lobectomy of EEIG, Uxbridge, United Kingdom), without developing sig- the lung, in order to excise a bronchiectasis, which was acting nificant toxicities, but he died in December 2016 due to the as a reservoir of bacteria. Besides a residual neurological progression of the disease. injury to his legs, no recurrences were later observed. &e patient also reported a history of moderate-to-severe plaque 3. Discussion psoriasis, previously treated with cyclosporine A, which was stopped in 2013. In clinical practice, every patient should be carefully in- In February 2015, he underwent surgical resection of terrogated about the personal and family history of immune cutaneous melanoma of the left gluteus, with the following disorders because it is one of the few acknowledged risk histopathological features: nodular melanoma, ulcerated, factors for development of irAEs [1]; following that diagnosis, Breslow thickness 9 mm, poorly pigmented, 12 mitoses/mm , it is impossible to quantify the risk of worsening/recurrence of Clark’s level IV, without regression and intra/peritumoral the preexisting autoimmune disease. Treatment decision lymphocytic infiltrate pT4b [22]. Wide surgical excision and should be made, properly weighing the expected clinical sentinel lymph node biopsy were negative for metastatic outcome and safety profile in each patient. &is kind of involvement (pathological stage IIC). In July 2015, positron- patients must be carefully monitored during a treatment with emission tomography (PET scan) showed pathological en- ICIs, in close collaboration with organ-specific consultants, in hancement of the retroperitoneal and left inguinal lymph order to diagnose as soon as possible a potential irAE. Our nodes (standardized uptake values from 2.6 to 22.5); therefore, patient had a history of GBS, a serious and life-threatening in September 2015, he underwent wide lymphadenectomy, disease, and at the same time a moderate psoriasis. &e Case Reports in Oncological Medicine 3 Motor nerve conduction study R. ext. Onset (ms) Duration (ms) Ampl. (mV) Area (μVs) Distance (cm) Speed (m/s) sciat-popliteal Ankle 5.9 9.2 1.8 4.0 9.0 Knee 14.7 10.9 1.3 14.3 40.0 45.5 +++++++++ 0–5000 Hz 50 ms Onset End 5 mV/Div 100 mA +++++++++ +++++++++ 0–5000 Hz 50 ms End 5 mV/Div Onset 100 mA +++++++++ +++++++++ +++++++++ Motor nerve conduction study R. int. Onset (ms) Duration (ms) Ampl. (mV) Area (μVs) Distance (cm) Speed (m/s) sciat-popliteal Inner malleol 6.3 15.4 1.1 4.8 10.0 Knee 16.5 14.2 0.8 2.3 39.0 38.6 +++++++++ +++++++++ 0–5000 Hz Onset 50 ms End 2 mV/Div 100 mA +++++++++ +++++++++ +++++++++ +++++++++ 0–5000 Hz Onset 50 ms End 2 mV/Div 100 mA +++++++++ +++++++++ Motor nerve conduction study L. ext. Onset (ms) Duration (ms) Ampl. (mV) Area (μVs) Distance (cm) Speed (m/s) sciat-popliteal 11.0 5.6 17.0 8.0 Ankle 4.5 14.7 Knee 14.0 11.0 4.1 38.0 40.0 +++++++++ 0–5000 Hz 50 ms Onset End 5 mV/Div 100 mA +++++++++ +++++++++ 0–5000 Hz 50 ms Onset End 5 mV/Div 100 mA +++++++++ +++++++++ +++++++++ Sensitive nerve conduction study Right sural Onset (ms) Duration (ms) Ampl. (mV) Area (μVs) Distance (cm) Speed (m/s) Calf 3.2 2.0 12.4 12.8 14.0 34.1 +++++++++ 20–2000 Hz 20 ms Peak 20 μV/Div 46 mA End +++++++++ Onset +++++++++ +++++++++ Figure 1 4 Case Reports in Oncological Medicine of immunotherapy,” Journal of Immunotherapy, vol. 40, no. 5, melanoma-related risk of developing symptoms and of death pp. 196–199, 2017. was higher than that of developing an irAE; therefore, the [11] B. van den Berg, C. Walgaard, J. Drenthen et al., absence of BRAF actionable mutations forced us to start “Guillain–Barre´ syndrome: pathogenesis, diagnosis, treat- a first-line treatment with ipilimumab, followed by ment and prognosis,” Nature Reviews Neurology, vol. 10, no. 8, pembrolizumab and nivolumab after disease progression. All pp. 469–482, 2014. the ICIs were well tolerated, without significant toxicities. [12] C. Robert, G. V. Long, B. Brady et al., “Nivolumab in pre- viously untreated melanoma without BRAF mutation,” New 4. Conclusion England Journal of Medicine, vol. 372, no. 4, pp. 320–330, &is case report supports the idea that, in some patients, it [13] J. Larkin, V. Chiarion-Sileni, R. Gonzalez et al., “Combined could be possible to safely administer sequential treatments nivolumab and ipilimumab or monotherapy in untreated with ICIs, although a history of preexisting immune disorders melanoma,” New England Journal of Medicine, vol. 373, no. 1, is one of the major risk factors for the development of irAEs. pp. 23–34, 2015. &e decision-making process should include a proper balance [14] R. S. Herbst, P. Baas, D. W. Kim et al., “Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced between the safety profile and expectations; alternatives should non-small-cell lung cancer (KEYNOTE-010): a randomised be discussed with patients and families, whose compliance is controlled trial,” /e Lancet, vol. 387, no. 10027, pp. 1540– fundamental to reach a good clinical outcome. 1550, 2016. [15] J. R. Brahmer, S. S. Tykodi, L. Chow et al., “Safety and activity Conflicts of Interest of anti-PDL-1 antibody in patients with advanced cancer,” New England Journal of Medicine, vol. 366, no. 26, pp. 2455– &e authors declare that they have no conflicts of interest. 2465, 2012. [16] N. Matsumara, M. Ohtsuka, N. Kikuchi, and T. Yamamoto, References “Exacerbation of psoriasis during nivolumab therapy for metastatic melanoma,” Acta Dermato-Venereologica, vol. 96, [1] S. Champiat, O. Lambotte, E. Barreau et al., “Management of no. 2, pp. 259-260, 2016. immune checkpoint blockade dysimmune toxicities: a col- [17] Y. Kato, A. Otsuka, Y. Miyachi, and K. Kabashima, “Exac- laborative position paper,” Annals of Oncology, vol. 27, no. 4, erbation of psoriasis vulgaris during nivolumab for oral pp. 559–574, 2016. mucosal melanoma,” Journal of the European Academy of [2] B. El Osta, F. Hu, R. Sadek, R. Chintalapally, and S.-C. Tang, Dermatology and Venereology, vol. 30, no. 10, pp. e89–e91, “A meta-analysis of immune-related adverse events (irAE) of immune checkpoint inhibitors (ICI) from cancer clinical [18] M. Ohtsuka, T. Miura, T. Mori, M. Ishikawa, and T. Yamamoto, trials,” Annals of Oncology, vol. 27, no. 6, 2016. “Occurrence of psoriasiform eruption during nivolumab ther- [3] F. S. Hodi, S. J. O’Day, D. F. McDermott et al., “Improved apy for primary oral mucosal melanoma,” JAMA Dermatology, survival with ipilimumab in patients with metastatic mela- vol. 151, no. 7, pp. 797–799, 2015. noma,” New England Journal of Medicine, vol. 363, no. 13, [19] M. B. Totonchy, H. H. Ezaldein, C. J. Ko, and J. N. Choi, pp. 711–723, 2010. “Inverse psoriasiform eruption during pembrolizumab ther- [4] J. Brahmer, K. L. Reckamp, P. Baas et al., “Nivolumab versus apy for metastatic melanoma,” JAMA Dermatology, vol. 152, docetaxel in advanced squamous-cell non–small-cell lung no. 5, pp. 590–592, 2016. cancer,” New England Journal of Medicine, vol. 373, no. 2, [20] D. B. Johnson, R. J. Sullivan, P. A. Ott et al., “Ipilimumab pp. 123–135, 2015. therapy in patients with advanced melanoma and preexist- [5] A. M. M. Eggermont, V. Chiarion-Sileni, J. J. Grob et al., ing autoimmune disorders,” JAMA Oncology, vol. 2, no. 2, “Prolonged survival in stage III melanoma with ipilimumab pp. 234–240, 2016. adjuvant therapy,” New England Journal of Medicine, vol. 375, [21] A. M. Menzies, D. B. Johnson, S. Ramanujam et al., “Anti-PD-1 no. 19, pp. 1845–1855, 2016. therapy in patients with advanced melanoma and preexisting [6] S. Wilgenhof and B. Neyns, “Anti-CTLA-4 antibody-induced autoimmune disorders or major toxicity with ipilimumab,” Guillain–Barre´ syndrome in a melanoma patient,” Annals of Annals of Oncology, vol. 28, no. 2, pp. 368–376, 2017. Oncology, vol. 22, no. 4, pp. 991–993, 2011. [22] S. B. Edge, D. R. Byrd, C. C. Compton et al., AJCC Cancer [7] I. Bot, C. U. Blank, W. Boogerd, and D. Brandsma, “Neu- Staging Manual, Springer, New York, NY, USA, 7th edition, rological immune-related adverse events of ipilimumab,” Practical Neurology, vol. 13, no. 4, pp. 278–280, 2013. [8] C. Gaudy-Marqueste, S. Monestier, J. Franques, E. Cantais, M.-A. Richard, and J.-J. Grob, “A severe case of ipilimumab- induced Guillain–Barre syndrome revealed by an occlusive enteric neuropathy: a differential diagnosis for ipilimumab- induced colitis,” Journal of Immunotherapy, vol. 36, no. 1, pp. 77-78, 2013. [9] V. Mukherjee, R. Postelnicu, D. Esaian, and D. Fridman, “An unusual cause of acute respiratory failure,” American Journal of Respiratory and Critical Care Medicine, vol. 189, p. A6185, [10] W. K. Wu, K. K. Broman, E. R. Brownie, and R. M. Kauffmann, “Ipilimumab-induced Guillain–Barre´ syndrome presenting as dysautonomia: an unusual presentation of a rare complication MEDIATORS of INFLAMMATION The Scientific Gastroenterology Journal of World Journal Research and Practice Diabetes Research Disease Markers Hindawi Hindawi Publishing Corporation Hindawi Hindawi Hindawi Hindawi www.hindawi.com Volume 2018 http://www www.hindawi.com .hindawi.com V Volume 2018 olume 2013 www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 International Journal of Journal of Immunology Research Endocrinology Hindawi Hindawi www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 Submit your manuscripts at www.hindawi.com BioMed PPAR Research Research International Hindawi Hindawi www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 Journal of Obesity Evidence-Based Journal of Journal of Stem Cells Complementary and Ophthalmology International Alternative Medicine Oncology Hindawi Hindawi Hindawi Hindawi Hindawi www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 www.hindawi.com Volume 2013 Parkinson’s Disease Computational and Behavioural Mathematical Methods AIDS Oxidative Medicine and in Medicine Neurology Research and Treatment Cellular Longevity Hindawi Hindawi Hindawi Hindawi Hindawi www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Case Reports in Oncological Medicine Hindawi Publishing Corporation

Safe Administration of Ipilimumab, Pembrolizumab, and Nivolumab in a Patient with Metastatic Melanoma, Psoriasis, and a Previous Guillain–Barré Syndrome

Download PDF
5 pages

Loading next page...
 
/lp/hindawi-publishing-corporation/safe-administration-of-ipilimumab-pembrolizumab-and-nivolumab-in-a-o1OxpzVdAl

References (29)

Publisher
Hindawi Publishing Corporation
Copyright
Copyright © 2018 Alessio Cortellini et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
ISSN
2090-6706
eISSN
2090-6714
DOI
10.1155/2018/2783917
Publisher site
See Article on Publisher Site

Abstract

Hindawi Case Reports in Oncological Medicine Volume 2018, Article ID 2783917, 4 pages https://doi.org/10.1155/2018/2783917 Case Report Safe Administration of Ipilimumab, Pembrolizumab, and Nivolumab in a Patient with Metastatic Melanoma, Psoriasis, and a Previous Guillain–Barre´ Syndrome 1,2 1,2 2,3 2 Alessio Cortellini , Alessandro Parisi, Maria Concetta Fargnoli, Katia Cannita, 1,2 1,2 4 1,2 Azzurra Irelli , Giampiero Porzio, Claudio Martinazzo, and Corrado Ficorella Medical Oncology Unit, St. Salvatore Hospital, L’Aquila, Italy Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila, L’Aquila, Italy Oncological Dermatology Unit, St. Salvatore Hospital, L’Aquila, Italy Department of Neurophysiopathology, St. Salvatore Hospital, L’Aquila, Italy Correspondence should be addressed to Alessio Cortellini; alessiocortellini@gmail.com Received 21 October 2017; Accepted 10 January 2018; Published 8 March 2018 Academic Editor: Jose I. Mayordomo Copyright © 2018 Alessio Cortellini et al. &is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background. Patients with autoimmune diseases were not evaluated in clinical trials with immune checkpoint inhibitors (ICIs), since a history of immune disorders, such as Guillain–Barre syndrome (GBS) and psoriasis, is one of the major risk factors for the development of immune-related adverse events (irAEs). &is risk cannot be defined; therefore, physicians are called to manage these patients in clinical practice. Case Report. We report the case of a 62-year-old male patient affected by metastatic melanoma, with a history of GBS and psoriasis, and treated with sequential ipilimumab, pembrolizumab, and nivolumab, without significant toxicities. Conclusion. &is case report supports that although a history of immune disorders is one of the major risk factors for development of irAEs, in some patients, it could be possible to safely administer sequential treatments with ICIs. A proper decision should be made, considering therapeutic options, disease-related risks, and those related to a recurrence of preexisting autoimmune disorders. more frequently related to ipilimumab than to nivolumab or 1. Introduction pembrolizumab; they are rare, occurring approximately in Before starting a treatment with immune checkpoint in- 1% of patients and up to 4.5% when referring to all neu- hibitors (ICIs), oncologists must identify potential risk fac- rological toxicities [2–5]. Guillain–Barre syndrome (GBS) is tors, such as previous or concomitant dysimmune disorders, an acute polyradiculoneuropathy with variable clinical presentation. &e pathogenesis of GBS is unclear, but it is that could favour the development of immune-related adverse events (irAEs). Unfortunately, patients with a history of well known that it is caused by cellular and humoral immune autoimmune diseases were not included in clinical trials; self-response against peripheral nerves. GBS could be however, after careful baseline assessment, they are more considered as an exceptional irAE with only five cases re- frequent than expected in common clinical practice. In this ported [6–10]. Numerous triggering events have been de- case, proper management, early diagnosis, and careful pre- scribed, such as infections; GBS can lead to death as a result and post-treatment monitoring of irAEs are required [1]. of complications (infections, thromboembolic events, re- IrAEs are reported more frequently with anti-CTLA4 (cyto- spiratory failure, and cardiac arrhythmias) in about 5% of toxic T-lymphocyte-associated antigen 4) monotherapy rather cases [11]. Skin disorders are the most frequent toxicity of than with anti-PD-1/PD-L1 (programmed death-1/programmed ICIs: overall incidence of dermatological irAEs appeared to be death-ligand 1) [2]. Immune-mediated polyneuropathies are similar with anti-CTLA4 and anti-PD-1/PD-L1. Considering 2 Case Reports in Oncological Medicine any grade, they occur from 10% to 60% (in combination resulting in 23 out of 42 metastatic lymph nodes; PETscan in therapy) of patients [3–5, 12–15]. Most cutaneous irAEs are December 2015 still demonstrated residual disease in the mild, reversible, and easily manageable following guidelines; retroperitoneal lymph nodes. He came to our attention at the they are often T-cell-mediated even if the pathophysiology is age of 62, in quite good clinical conditions, with eastern still unknown. Psoriasis is a multifactorial immune-mediated cooperative oncology group performance status (ECOG-PS) chronic cutaneous disease, characterized by a wide range of 1. &e BRAF mutational analysis (V600) was negative clinical manifestations from mild to severe forms. Worsening (cobas z 480 analyzer). &e high tumor burden, with LDH and recurrence of psoriasis have been reported during the use more than 2 ULN, and the absence of an actionable BRAF of ICIs, with both anti-CTLA4 and anti-PD-1, such as niv- mutation led us to choose a first-line treatment with immune olumab [16–20]. Recently, a case series of advanced melanoma checkpoint inhibitors (ICIs). At that time, the only “in-label” patients treated with anti-PD-1 therapy and with preexisting drug in Italy for first-line treatment of BRAF wild-type autoimmune disorders has included 2 patients with a history advanced melanoma patients was ipilimumab (Yervoy ; of GBS (none of them experienced a worsening/flare) and Bristol-Myers Squibb Pharma EEIG, Uxbridge, United 6 patients with a history of psoriasis (3 of them experienced Kingdom). Before starting ipilimumab, we made a careful cutaneous irAEs) [21]. We report the case of a 62-year-old multidisciplinary assessment with dermatological and neu- male patient, with metastatic melanoma and a history of GBS rological evaluation. On dermatological evaluation, the pa- and psoriasis. &e patient was treated with sequential tient presented psoriatic plaques on the trunk and extremities; ipilimumab, pembrolizumab, and nivolumab, without sig- a baseline EMG was performed that showed the residual nificant toxicities or worsening of the preexisting autoimmune functional loss, mainly to the legs (Figure 1). disorders. &e patient was treated in clinical practice with “in- From December 11, 2015, to February 19, 2016, 4 induction label” drugs in Italy and provided written informed consent to doses of ipilimumab (3 mg/kg every three weeks) were ad- the proposed treatment; procedures followed in reporting the ministered without significant toxicities, except development case are in accordance with the ethical standard of the local of cutaneous facial vitiligo on the face; psoriatic plaques responsible committee on human experimentation. remained unchanged, and the patient did not develop new neurological symptoms. A CT scan in March 2016 showed an immune-related response of disease (dimensional reduction 2. Case Presentation and intralesional necrosis) and also detected a pulmonary We report the case of a male patient, a smoker, with a history embolism, treated with low molecular weight heparin. In of chronic obstructive lung disease, atrial fibrillation, hy- April 2016, the CT scan showed resolution of pulmonary pertension, obesity, chronic plaque psoriasis, and Guillain– embolism, and neurological evaluation showed no changes, Barre´ syndrome (GBS). &e diagnosis of GBS dated back to just like the control EMG that was performed. 2002; during a community-acquired pneumonia, a molecular In June 2016, the CT scan showed progressive disease to mimetism between bacterial antigens and gangliosides of the the lymph nodes; therefore, the patient underwent a second- nerves’ myelin sheath led to the development of a severe and line therapy with pembrolizumab (2 mg/kg every three rapidly progressive muscle weakness with areflexia, till tet- weeks) (Keytruda ; Merck Sharp & Dohme Limited, Hoddesdon, raplegia. Electromyography (EMG) confirmed acute, axonal United Kingdom), with only one dose administered, on July 11. polyneuropathy, with reduced sensory action potential, After that, he decided to continue the treatment at an outpatient supporting the diagnosis of the “acute motor and sensory cancer care center closer to his home. From October to axonal neuropathy” (AMSAN) type of GBS. &e patient was November 2016, he received 3 doses of nivolumab (3 mg/kg hospitalized and successfully treated with intravenous im- every two weeks) (Opdivo ; Bristol-Myers Squibb Pharma munoglobulins; he then underwent upper left lobectomy of EEIG, Uxbridge, United Kingdom), without developing sig- the lung, in order to excise a bronchiectasis, which was acting nificant toxicities, but he died in December 2016 due to the as a reservoir of bacteria. Besides a residual neurological progression of the disease. injury to his legs, no recurrences were later observed. &e patient also reported a history of moderate-to-severe plaque 3. Discussion psoriasis, previously treated with cyclosporine A, which was stopped in 2013. In clinical practice, every patient should be carefully in- In February 2015, he underwent surgical resection of terrogated about the personal and family history of immune cutaneous melanoma of the left gluteus, with the following disorders because it is one of the few acknowledged risk histopathological features: nodular melanoma, ulcerated, factors for development of irAEs [1]; following that diagnosis, Breslow thickness 9 mm, poorly pigmented, 12 mitoses/mm , it is impossible to quantify the risk of worsening/recurrence of Clark’s level IV, without regression and intra/peritumoral the preexisting autoimmune disease. Treatment decision lymphocytic infiltrate pT4b [22]. Wide surgical excision and should be made, properly weighing the expected clinical sentinel lymph node biopsy were negative for metastatic outcome and safety profile in each patient. &is kind of involvement (pathological stage IIC). In July 2015, positron- patients must be carefully monitored during a treatment with emission tomography (PET scan) showed pathological en- ICIs, in close collaboration with organ-specific consultants, in hancement of the retroperitoneal and left inguinal lymph order to diagnose as soon as possible a potential irAE. Our nodes (standardized uptake values from 2.6 to 22.5); therefore, patient had a history of GBS, a serious and life-threatening in September 2015, he underwent wide lymphadenectomy, disease, and at the same time a moderate psoriasis. &e Case Reports in Oncological Medicine 3 Motor nerve conduction study R. ext. Onset (ms) Duration (ms) Ampl. (mV) Area (μVs) Distance (cm) Speed (m/s) sciat-popliteal Ankle 5.9 9.2 1.8 4.0 9.0 Knee 14.7 10.9 1.3 14.3 40.0 45.5 +++++++++ 0–5000 Hz 50 ms Onset End 5 mV/Div 100 mA +++++++++ +++++++++ 0–5000 Hz 50 ms End 5 mV/Div Onset 100 mA +++++++++ +++++++++ +++++++++ Motor nerve conduction study R. int. Onset (ms) Duration (ms) Ampl. (mV) Area (μVs) Distance (cm) Speed (m/s) sciat-popliteal Inner malleol 6.3 15.4 1.1 4.8 10.0 Knee 16.5 14.2 0.8 2.3 39.0 38.6 +++++++++ +++++++++ 0–5000 Hz Onset 50 ms End 2 mV/Div 100 mA +++++++++ +++++++++ +++++++++ +++++++++ 0–5000 Hz Onset 50 ms End 2 mV/Div 100 mA +++++++++ +++++++++ Motor nerve conduction study L. ext. Onset (ms) Duration (ms) Ampl. (mV) Area (μVs) Distance (cm) Speed (m/s) sciat-popliteal 11.0 5.6 17.0 8.0 Ankle 4.5 14.7 Knee 14.0 11.0 4.1 38.0 40.0 +++++++++ 0–5000 Hz 50 ms Onset End 5 mV/Div 100 mA +++++++++ +++++++++ 0–5000 Hz 50 ms Onset End 5 mV/Div 100 mA +++++++++ +++++++++ +++++++++ Sensitive nerve conduction study Right sural Onset (ms) Duration (ms) Ampl. (mV) Area (μVs) Distance (cm) Speed (m/s) Calf 3.2 2.0 12.4 12.8 14.0 34.1 +++++++++ 20–2000 Hz 20 ms Peak 20 μV/Div 46 mA End +++++++++ Onset +++++++++ +++++++++ Figure 1 4 Case Reports in Oncological Medicine of immunotherapy,” Journal of Immunotherapy, vol. 40, no. 5, melanoma-related risk of developing symptoms and of death pp. 196–199, 2017. was higher than that of developing an irAE; therefore, the [11] B. van den Berg, C. Walgaard, J. Drenthen et al., absence of BRAF actionable mutations forced us to start “Guillain–Barre´ syndrome: pathogenesis, diagnosis, treat- a first-line treatment with ipilimumab, followed by ment and prognosis,” Nature Reviews Neurology, vol. 10, no. 8, pembrolizumab and nivolumab after disease progression. All pp. 469–482, 2014. the ICIs were well tolerated, without significant toxicities. [12] C. Robert, G. V. Long, B. Brady et al., “Nivolumab in pre- viously untreated melanoma without BRAF mutation,” New 4. Conclusion England Journal of Medicine, vol. 372, no. 4, pp. 320–330, &is case report supports the idea that, in some patients, it [13] J. Larkin, V. Chiarion-Sileni, R. Gonzalez et al., “Combined could be possible to safely administer sequential treatments nivolumab and ipilimumab or monotherapy in untreated with ICIs, although a history of preexisting immune disorders melanoma,” New England Journal of Medicine, vol. 373, no. 1, is one of the major risk factors for the development of irAEs. pp. 23–34, 2015. &e decision-making process should include a proper balance [14] R. S. Herbst, P. Baas, D. W. Kim et al., “Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced between the safety profile and expectations; alternatives should non-small-cell lung cancer (KEYNOTE-010): a randomised be discussed with patients and families, whose compliance is controlled trial,” /e Lancet, vol. 387, no. 10027, pp. 1540– fundamental to reach a good clinical outcome. 1550, 2016. [15] J. R. Brahmer, S. S. Tykodi, L. Chow et al., “Safety and activity Conflicts of Interest of anti-PDL-1 antibody in patients with advanced cancer,” New England Journal of Medicine, vol. 366, no. 26, pp. 2455– &e authors declare that they have no conflicts of interest. 2465, 2012. [16] N. Matsumara, M. Ohtsuka, N. Kikuchi, and T. Yamamoto, References “Exacerbation of psoriasis during nivolumab therapy for metastatic melanoma,” Acta Dermato-Venereologica, vol. 96, [1] S. Champiat, O. Lambotte, E. Barreau et al., “Management of no. 2, pp. 259-260, 2016. immune checkpoint blockade dysimmune toxicities: a col- [17] Y. Kato, A. Otsuka, Y. Miyachi, and K. Kabashima, “Exac- laborative position paper,” Annals of Oncology, vol. 27, no. 4, erbation of psoriasis vulgaris during nivolumab for oral pp. 559–574, 2016. mucosal melanoma,” Journal of the European Academy of [2] B. El Osta, F. Hu, R. Sadek, R. Chintalapally, and S.-C. Tang, Dermatology and Venereology, vol. 30, no. 10, pp. e89–e91, “A meta-analysis of immune-related adverse events (irAE) of immune checkpoint inhibitors (ICI) from cancer clinical [18] M. Ohtsuka, T. Miura, T. Mori, M. Ishikawa, and T. Yamamoto, trials,” Annals of Oncology, vol. 27, no. 6, 2016. “Occurrence of psoriasiform eruption during nivolumab ther- [3] F. S. Hodi, S. J. O’Day, D. F. McDermott et al., “Improved apy for primary oral mucosal melanoma,” JAMA Dermatology, survival with ipilimumab in patients with metastatic mela- vol. 151, no. 7, pp. 797–799, 2015. noma,” New England Journal of Medicine, vol. 363, no. 13, [19] M. B. Totonchy, H. H. Ezaldein, C. J. Ko, and J. N. Choi, pp. 711–723, 2010. “Inverse psoriasiform eruption during pembrolizumab ther- [4] J. Brahmer, K. L. Reckamp, P. Baas et al., “Nivolumab versus apy for metastatic melanoma,” JAMA Dermatology, vol. 152, docetaxel in advanced squamous-cell non–small-cell lung no. 5, pp. 590–592, 2016. cancer,” New England Journal of Medicine, vol. 373, no. 2, [20] D. B. Johnson, R. J. Sullivan, P. A. Ott et al., “Ipilimumab pp. 123–135, 2015. therapy in patients with advanced melanoma and preexist- [5] A. M. M. Eggermont, V. Chiarion-Sileni, J. J. Grob et al., ing autoimmune disorders,” JAMA Oncology, vol. 2, no. 2, “Prolonged survival in stage III melanoma with ipilimumab pp. 234–240, 2016. adjuvant therapy,” New England Journal of Medicine, vol. 375, [21] A. M. Menzies, D. B. Johnson, S. Ramanujam et al., “Anti-PD-1 no. 19, pp. 1845–1855, 2016. therapy in patients with advanced melanoma and preexisting [6] S. Wilgenhof and B. Neyns, “Anti-CTLA-4 antibody-induced autoimmune disorders or major toxicity with ipilimumab,” Guillain–Barre´ syndrome in a melanoma patient,” Annals of Annals of Oncology, vol. 28, no. 2, pp. 368–376, 2017. Oncology, vol. 22, no. 4, pp. 991–993, 2011. [22] S. B. Edge, D. R. Byrd, C. C. Compton et al., AJCC Cancer [7] I. Bot, C. U. Blank, W. Boogerd, and D. Brandsma, “Neu- Staging Manual, Springer, New York, NY, USA, 7th edition, rological immune-related adverse events of ipilimumab,” Practical Neurology, vol. 13, no. 4, pp. 278–280, 2013. [8] C. Gaudy-Marqueste, S. Monestier, J. Franques, E. Cantais, M.-A. Richard, and J.-J. Grob, “A severe case of ipilimumab- induced Guillain–Barre syndrome revealed by an occlusive enteric neuropathy: a differential diagnosis for ipilimumab- induced colitis,” Journal of Immunotherapy, vol. 36, no. 1, pp. 77-78, 2013. [9] V. Mukherjee, R. Postelnicu, D. Esaian, and D. Fridman, “An unusual cause of acute respiratory failure,” American Journal of Respiratory and Critical Care Medicine, vol. 189, p. A6185, [10] W. K. Wu, K. K. Broman, E. R. Brownie, and R. M. Kauffmann, “Ipilimumab-induced Guillain–Barre´ syndrome presenting as dysautonomia: an unusual presentation of a rare complication MEDIATORS of INFLAMMATION The Scientific Gastroenterology Journal of World Journal Research and Practice Diabetes Research Disease Markers Hindawi Hindawi Publishing Corporation Hindawi Hindawi Hindawi Hindawi www.hindawi.com Volume 2018 http://www www.hindawi.com .hindawi.com V Volume 2018 olume 2013 www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 International Journal of Journal of Immunology Research Endocrinology Hindawi Hindawi www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 Submit your manuscripts at www.hindawi.com BioMed PPAR Research Research International Hindawi Hindawi www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 Journal of Obesity Evidence-Based Journal of Journal of Stem Cells Complementary and Ophthalmology International Alternative Medicine Oncology Hindawi Hindawi Hindawi Hindawi Hindawi www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 www.hindawi.com Volume 2013 Parkinson’s Disease Computational and Behavioural Mathematical Methods AIDS Oxidative Medicine and in Medicine Neurology Research and Treatment Cellular Longevity Hindawi Hindawi Hindawi Hindawi Hindawi www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 www.hindawi.com Volume 2018

Journal

Case Reports in Oncological Medicine – Hindawi Publishing Corporation

Published: Mar 8, 2018

There are no references for this article.