- Email: [email protected]
Immune checkpoints inhibitors for solid tumours after allogeneic haematopoietic stem-cell transplantation: About four clinical cases
European Journal of Cancer 81 (2017) 138e141
Available online at www.sciencedirect.com
ScienceDirect journal homepage: www.ejcancer.com
Immune checkpoints inhibitors for solid tumours after allogeneic haematopoietic stem-cell transplantation: About four clinical cases Audrey Monneur a,b, Jilliana Monnier c, Caroline Gaudy-Marqueste c, Raynier Devillier b,d, Renaud Sabatier a,b,* a
Department of Medical Oncology, Institut Paoli-Calmettes, Marseille, France Aix Marseille Univ, CNRS U7258, INSERM U1068, Institut Paoli-Calmettes, CRCM, Marseille, France c Department of Dermatology, Hoˆpital de La Timone, Assistance Publique Hoˆpitaux de Marseille, Aix-Marseille Univ, Marseille, France d Department of Haematology, Institut Paoli-Calmettes, Marseille, France b
Received 4 April 2017; accepted 11 May 2017
Immunotherapy, and particularly immune checkpoint inhibitors (ICI), represents one of the best advances in oncology in the last decade. Drugs which block the immune checkpoints (mainly PD-1/PD-L1 and CTLA-4) pathway have shown durable objective responses for advanced various solid malignancies including melanoma [1e3] and nonesmall cell lung carcinoma [4e6]. CTLA-4 is a negative regulator of Tcell activation [7], which can be inactivated by ipilimumab, a recombinant human monoclonal antibody that avoids CTLA-4 binding to its ligand. Nivolumab and pembrolizumab are human monoclonal antibodies that block the interaction between programmed cell death protein 1 receptor (PD-1) and its ligands (PD-L1 and PD-L2) leading to a decrease in PD-1emediated inhibition of the immune response [8]. CTLA-4 and PD-1 pathways are also involved in limiting excessive T-cell activation and prevention of auto-immunity [9]. Allogeneic haematopoietic stem-cell transplantation
* Corresponding author: Department of Medical Oncology, Institut Paoli-Calmettes, 232 Boulevard Sainte Marguerite, 13009 Marseille, France. E-mail address: [email protected] (R. Sabatier). http://dx.doi.org/10.1016/j.ejca.2017.05.023 0959-8049/ª 2017 Elsevier Ltd. All rights reserved.
(AHSCT) is an option to treat high-risk or refractory haematological malignancies. Acute and chronic graft versus host diseases (GVHD) are the main adverse events linked to this therapy. Immunological mechanisms of GVHD are in part related to PD-L1 expression level on donor T cells in murine models [10], and one case of lethal GVHD after PD-1einhibitor treatment for refractory Hodgkin disease has recently been published [11]. We wondered how ICI could be safe and efficient after AHSCT for a haematological malignancy. We report here four cases of patients diagnosed with secondary solid cancer after AHSCT and treated with ICI (see Table 1). 1. Clinical case 1 A 52-year-old man treated for a refractory mantle cell lymphoma displayed acute and chronic GVHD after AHSCT which was successfully treated with corticosteroids. Five years later, he was diagnosed with stage IV metastatic lung adenocarcinoma with KRAS mutation. He successively received a platinum-based doublet followed with pemetrexed maintenance. After chemotherapy failure he received nivolumab for 1 month.
A. Monneur et al. / European Journal of Cancer 81 (2017) 138e141
139
Table 1 Main clinicopathological features related to previous haematological disease, solid tumour, as well as immune checkpoint inhibitor therapy. Clinicopathological features
Patient-01
Patient-02
Patient-03
Patient-04
Haematological disease
Mantle cell lymphoma
Mantle cell lymphoma
Acute GVHD Chronic GVHD GVHD treatment Delay between AHSCT and solid tumour diagnosis Smoking history
Cutaneous Cutaneous Steroids 5 years
Acute myeloid leukaemia type 6 Digestive Mucous Mycophe´nolate mofe´til 7 years
Chronic lymphocytic leukaemia None Cutaneous and digestive Steroids; ciclosporin 6 years
50 PY (stopped at 40 years)
Cutaneous and hepatic Cutaneous and hepatic Steroids 9 years
Tumour type
Metastatic lung adenocarcinoma
Molecular alteration Type of immunotherapy
KRAS mutation Nivolumab
30 PY (stopped at 53 years) Metastatic lung adenocarcinoma; bladder cancer None Nivolumab
25 PY (stopped at 52 years) Metastatic lung adenocarcinoma
IrAE
None
None
None
Treatment duration
1 month
3 months
Ongoing after 6 months of follow-up
Cause of treatment discontinuation
Early cerebral progression
Hepatic and pleural progression
NA
None Nivolumab
NA Melanoma
None Pembrolizumab, ipilimumab and nivolumab Fulminant type 1 diabetes Adjuvant pembrolizumab: 6 months; ipilimumab: 3 months; nivolumab: 4 months Cerebral and systemic progression
GVHD, graft versus host disease; AHSCT, allogeneic haematopoietic stem-cell transplantation; NA, non-assessable; IrAE, immune-related adverse event.
Nivolumab was stopped because of cerebral progression requiring corticosteroids, but without any adverse event. He finally died of pneumocystis pneumonia a few months later. 2. Clinical case 2 A 66-year-old man received an AHSCT for a refractory acute myeloid leukaemia (AML-6). He presented acute and chronic GVHD, successfully treated with mycophenolate mofetil. Seven years later, he was diagnosed with stage IV metastatic lung adenocarcinoma, without any molecular alteration. He experienced disease progression after one line of platinum-based chemotherapy and was concomitantly diagnosed with a bladder cancer. He received nivolumab after lung cancer progression. Even though he had no adverse event under nivolumab, immunotherapy was discontinued after 3 months because of multi-metastatic progression of lung cancer and likely bladder cancer. 3. Clinical case 3 A 52-year-old man received an AHSCT for a refractory mantle cell lymphoma and presented acute and chronic GVHD requiring corticosteroids. Nine years later, he was diagnosed with a localised (T2N0M0) poorly differentiated lung adenocarcinoma and underwent
surgery. He presented a metastatic relapse 6 months after surgery treated with induction chemotherapy (platinum, pemetrexed and bevacizumab combination) followed by continuation maintenance (pemetrexed and bevacizumab combination) during 3 months. Because of disease progression, he received nivolumab, which is still ongoing with no adverse event. computed tomographyscan at 6 months showed a partial response. 4. Clinical case 4 A 42-year-old man received an AHSCT for a chronic lymphocytic leukaemia, with subsequent chronic cutaneous and digestive GVHD treated with steroids and ciclosporin. Six years later a scalp subcutaneous metastasis of melanoma, with no BRAF and NRAS mutations was resected. The primary melanoma could not be identified. One year later a cervical node was surgically resected and the patient was enrolled in an adjuvant clinical trial assessing the efficacy of pembrolizumab versus placebo. The treatment was stopped after 6 months because of disease progression. He received ipilimumab for four injections without efficacy and then started a second line of treatment with nivolumab. Two months after he was diagnosed with fulminant type 1 diabetes, nivolumab was maintained for 2 months despite this adverse event before a cerebral and systemic progression was observed. The patient died few weeks later.
140
A. Monneur et al. / European Journal of Cancer 81 (2017) 138e141
5. Discussion
References
Advances in AHSCT and supportive care have contributed to greater number of long-term survivors who remain free of their original disease [9]. However transplants recipients display a 2e3 fold higher risk of developing secondary solid malignancies compared with general population [10,11]. ICI have improved outcomes in advanced various solid malignancies including melanoma. Information about safety of ICI is essential for AHSCT recipients. Only few cases reporting efficacy and toxicity of ICI for solid organ transplant recipients have been published so far. Successful administration of ICI in liver and kidney transplant recipients without any toxicity has been described in the context of refractory melanoma [12e15]. Interestingly, one case of acute graft rejection has been described for a kidney transplant recipient receiving nivolumab after progression under ipilimumab for metastatic melanoma [16]. However, ICI management for organ transplant recipients remains poorly known [17]. To our knowledge, there is no such data in AHSCT recipients presenting subsequent solid tumours. Given the ability of ICI to activate T-cell, we could expect a GVHD reactivation, as it has been described in patients with relapsed haematological malignancies [18]. Despite that all our patients presented acute and chronic GVHD, there was no GVHD reactivation while they were no longer under immunosuppressive treatment. This may be explained by the delay between GVHD resolution and ICI initiation. One of our patients experienced fulminant type 1 diabetes, a rare adverse event described to be possibly related to auto-immune reaction [19]. It has been recently described in some patients receiving ICI, especially nivolumab, suggesting that T-cell activation could be involved in such phenomenon [20e22]. Moreover, one can also predict that ICI efficacy can be modified after AHSCT. Even though the small sample size does not allow any efficacy analysis, we observed that one patient among the four cases described here had a clinical benefit under nivolumab. This observation suggesting that ICI can be efficient after AHSCT obviously deserves to be confirmed in larger studies. Our data may be useful to clinicians who have to treat such patients.
[1] Robert C, Thomas L, Bondarenko I, O’Day S, Weber J, Garbe C, et al. Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. N Engl J Med 2011;364:2517e26. http: //dx.doi.org/10.1056/NEJMoa1104621. [2] Robert C, Schachter J, Long GV, Arance A, Grob JJ, Mortier L, et al. Pembrolizumab versus ipilimumab in advanced melanoma. N Engl J Med 2015;372:2521e32. http://dx.doi.org/10.1056/ NEJMoa1503093. [3] Hodi FS, O’Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 2010;363:711e23. http: //dx.doi.org/10.1056/NEJMoa1003466. [4] Brahmer J, Reckamp KL, Baas P, Crino` L, Eberhardt WEE, Poddubskaya E, et al. Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer. N Engl J Med 2015; 373:123e35. http://dx.doi.org/10.1056/NEJMoa1504627. [5] Borghaei H, Paz-Ares L, Horn L, Spigel DR, Steins M, Ready NE, et al. Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. N Engl J Med 2015;373: 1627e39. http://dx.doi.org/10.1056/NEJMoa1507643. [6] Reck M, Rodrı´guez-Abreu D, Robinson AG, Hui R, Cs} oszi T, Fu¨lo¨p A, et al. Pembrolizumab versus chemotherapy for PD-L1positive non-small-cell lung cancer. N Engl J Med 2016. http: //dx.doi.org/10.1056/NEJMoa1606774. [7] Lafage-Pochitaloff M, Costello R, Couez D, Simonetti J, Mannoni P, Mawas C, et al. Human CD28 and CTLA-4 Ig superfamily genes are located on chromosome 2 at bands q33-q34. Immunogenetics 1990;31:198e201. [8] Ishida Y, Agata Y, Shibahara K, Honjo T. Induced expression of PD-1, a novel member of the immunoglobulin gene superfamily, upon programmed cell death. EMBO J 1992;11:3887e95. [9] Gooley TA, Chien JW, Pergam SA, Hingorani S, Sorror ML, Boeckh M, et al. Reduced mortality after allogeneic hematopoieticcell transplantation. N Engl J Med 2010;363:2091e101. http: //dx.doi.org/10.1056/NEJMoa1004383. [10] Rizzo JD, Curtis RE, Socie´ G, Sobocinski KA, Gilbert E, Landgren O, et al. Solid cancers after allogeneic hematopoietic cell transplantation. Blood 2009;113:1175e83. http://dx.doi.org/10. 1182/blood-2008-05-158782. [11] Baker KS, DeFor TE, Burns LJ, Ramsay NKC, Neglia JP, Robison LL. New malignancies after blood or marrow stem-cell transplantation in children and adults: incidence and risk factors. J Clin Oncol Off J Am Soc Clin Oncol 2003;21:1352e8. http: //dx.doi.org/10.1200/JCO.2003.05.108. [12] Morales RE, Shoushtari AN, Walsh MM, Grewal P, Lipson EJ, Carvajal RD. Safety and efficacy of ipilimumab to treat advanced melanoma in the setting of liver transplantation. J Immunother Cancer 2015;3:22. http://dx.doi.org/10.1186/s40425-015-0066-0. [13] Lipson EJ, Bodell MA, Kraus ES, Sharfman WH. Successful administration of ipilimumab to two kidney transplantation patients with metastatic melanoma. J Clin Oncol Off J Am Soc Clin Oncol 2014;32:e69e71. http://dx.doi.org/10.1200/JCO.2013.49.2314. [14] Herz S, Ho¨fer T, Papapanagiotou M, Leyh JC, Meyenburg S, Schadendorf D, et al. Checkpoint inhibitors in chronic kidney failure and an organ transplant recipient. Eur J Cancer Oxf Engl 2016;67:66e72. http://dx.doi.org/10.1016/j.ejca.2016.07.026. 1990. [15] Ranganath HA, Panella TJ. Administration of ipilimumab to a liver transplant recipient with unresectable metastatic melanoma. J Immunother Hagerst Md 2015;38:211. http://dx.doi.org/10. 1097/CJI.0000000000000077. 1997. [16] Spain L, Higgins R, Gopalakrishnan K, Turajlic S, Gore M, Larkin J. Acute renal allograft rejection after immune checkpoint inhibitor therapy for metastatic melanoma. Ann Oncol Off J Eur Soc Med Oncol 2016;27:1135e7. http://dx.doi.org/10.1093/annonc/ mdw130.
Conflict of interest statement RS has received consulting fees from BMS. CGM has received consulting fees and travel grants from BMS. The other authors have no disclosure to declare. Funding This work has been funded by Institut Paoli-Calmettes and SIRIC (INCa-DGOSInserm 6038).
A. Monneur et al. / European Journal of Cancer 81 (2017) 138e141 [17] Maggiore U, Pascual J. The bad and the good news on cancer immunotherapy: implications for organ transplant recipients. Adv Chronic Kidney Dis 2016;23:312e6. http://dx.doi.org/10.1053/ j.ackd.2016.08.002. [18] Davids MS, Kim HT, Bachireddy P, Costello C, Liguori R, Savell A, et al. Ipilimumab for patients with relapse after allogeneic transplantation. N Engl J Med 2016;375:143e53. http: //dx.doi.org/10.1056/NEJMoa1601202. [19] Imagawa A, Hanafusa T. Pathogenesis of fulminant type 1 diabetes. Rev Diabet Stud RDS 2006;3:169e77. http://dx.doi.org/10. 1900/RDS.2006.3.169. [20] Okamoto M, Okamoto M, Gotoh K, Masaki T, Ozeki Y, Ando H, et al. Fulminant type 1 diabetes mellitus with anti-programmed
141
cell death-1 therapy. J Diabetes Investig 2016;7:915e8. http: //dx.doi.org/10.1111/jdi.12531. [21] Ishikawa K, Shono-Saito T, Yamate T, Kai Y, Sakai T, Shimizu F, et al. A case of fulminant type 1 diabetes mellitus, with a precipitous decrease in pancreatic volume, induced by nivolumab for malignant melanoma: analysis of HLA and CTLA-4 polymorphisms. Eur J Dermatol 2016. http://dx.doi.org/10.1684/ ejd.2016.2923. [22] Gaudy C, Cle´vy C, Monestier S, Dubois N, Pre´au Y, Mallet S, et al. Anti-PD1 pembrolizumab can induce exceptional fulminant type 1 diabetes. Diabetes Care 2015;38:e182e183. http://dx.doi.org/10. 2337/dc15-1331.
Available online at www.sciencedirect.com
ScienceDirect journal homepage: www.ejcancer.com
Immune checkpoints inhibitors for solid tumours after allogeneic haematopoietic stem-cell transplantation: About four clinical cases Audrey Monneur a,b, Jilliana Monnier c, Caroline Gaudy-Marqueste c, Raynier Devillier b,d, Renaud Sabatier a,b,* a
Department of Medical Oncology, Institut Paoli-Calmettes, Marseille, France Aix Marseille Univ, CNRS U7258, INSERM U1068, Institut Paoli-Calmettes, CRCM, Marseille, France c Department of Dermatology, Hoˆpital de La Timone, Assistance Publique Hoˆpitaux de Marseille, Aix-Marseille Univ, Marseille, France d Department of Haematology, Institut Paoli-Calmettes, Marseille, France b
Received 4 April 2017; accepted 11 May 2017
Immunotherapy, and particularly immune checkpoint inhibitors (ICI), represents one of the best advances in oncology in the last decade. Drugs which block the immune checkpoints (mainly PD-1/PD-L1 and CTLA-4) pathway have shown durable objective responses for advanced various solid malignancies including melanoma [1e3] and nonesmall cell lung carcinoma [4e6]. CTLA-4 is a negative regulator of Tcell activation [7], which can be inactivated by ipilimumab, a recombinant human monoclonal antibody that avoids CTLA-4 binding to its ligand. Nivolumab and pembrolizumab are human monoclonal antibodies that block the interaction between programmed cell death protein 1 receptor (PD-1) and its ligands (PD-L1 and PD-L2) leading to a decrease in PD-1emediated inhibition of the immune response [8]. CTLA-4 and PD-1 pathways are also involved in limiting excessive T-cell activation and prevention of auto-immunity [9]. Allogeneic haematopoietic stem-cell transplantation
* Corresponding author: Department of Medical Oncology, Institut Paoli-Calmettes, 232 Boulevard Sainte Marguerite, 13009 Marseille, France. E-mail address: [email protected] (R. Sabatier). http://dx.doi.org/10.1016/j.ejca.2017.05.023 0959-8049/ª 2017 Elsevier Ltd. All rights reserved.
(AHSCT) is an option to treat high-risk or refractory haematological malignancies. Acute and chronic graft versus host diseases (GVHD) are the main adverse events linked to this therapy. Immunological mechanisms of GVHD are in part related to PD-L1 expression level on donor T cells in murine models [10], and one case of lethal GVHD after PD-1einhibitor treatment for refractory Hodgkin disease has recently been published [11]. We wondered how ICI could be safe and efficient after AHSCT for a haematological malignancy. We report here four cases of patients diagnosed with secondary solid cancer after AHSCT and treated with ICI (see Table 1). 1. Clinical case 1 A 52-year-old man treated for a refractory mantle cell lymphoma displayed acute and chronic GVHD after AHSCT which was successfully treated with corticosteroids. Five years later, he was diagnosed with stage IV metastatic lung adenocarcinoma with KRAS mutation. He successively received a platinum-based doublet followed with pemetrexed maintenance. After chemotherapy failure he received nivolumab for 1 month.
A. Monneur et al. / European Journal of Cancer 81 (2017) 138e141
139
Table 1 Main clinicopathological features related to previous haematological disease, solid tumour, as well as immune checkpoint inhibitor therapy. Clinicopathological features
Patient-01
Patient-02
Patient-03
Patient-04
Haematological disease
Mantle cell lymphoma
Mantle cell lymphoma
Acute GVHD Chronic GVHD GVHD treatment Delay between AHSCT and solid tumour diagnosis Smoking history
Cutaneous Cutaneous Steroids 5 years
Acute myeloid leukaemia type 6 Digestive Mucous Mycophe´nolate mofe´til 7 years
Chronic lymphocytic leukaemia None Cutaneous and digestive Steroids; ciclosporin 6 years
50 PY (stopped at 40 years)
Cutaneous and hepatic Cutaneous and hepatic Steroids 9 years
Tumour type
Metastatic lung adenocarcinoma
Molecular alteration Type of immunotherapy
KRAS mutation Nivolumab
30 PY (stopped at 53 years) Metastatic lung adenocarcinoma; bladder cancer None Nivolumab
25 PY (stopped at 52 years) Metastatic lung adenocarcinoma
IrAE
None
None
None
Treatment duration
1 month
3 months
Ongoing after 6 months of follow-up
Cause of treatment discontinuation
Early cerebral progression
Hepatic and pleural progression
NA
None Nivolumab
NA Melanoma
None Pembrolizumab, ipilimumab and nivolumab Fulminant type 1 diabetes Adjuvant pembrolizumab: 6 months; ipilimumab: 3 months; nivolumab: 4 months Cerebral and systemic progression
GVHD, graft versus host disease; AHSCT, allogeneic haematopoietic stem-cell transplantation; NA, non-assessable; IrAE, immune-related adverse event.
Nivolumab was stopped because of cerebral progression requiring corticosteroids, but without any adverse event. He finally died of pneumocystis pneumonia a few months later. 2. Clinical case 2 A 66-year-old man received an AHSCT for a refractory acute myeloid leukaemia (AML-6). He presented acute and chronic GVHD, successfully treated with mycophenolate mofetil. Seven years later, he was diagnosed with stage IV metastatic lung adenocarcinoma, without any molecular alteration. He experienced disease progression after one line of platinum-based chemotherapy and was concomitantly diagnosed with a bladder cancer. He received nivolumab after lung cancer progression. Even though he had no adverse event under nivolumab, immunotherapy was discontinued after 3 months because of multi-metastatic progression of lung cancer and likely bladder cancer. 3. Clinical case 3 A 52-year-old man received an AHSCT for a refractory mantle cell lymphoma and presented acute and chronic GVHD requiring corticosteroids. Nine years later, he was diagnosed with a localised (T2N0M0) poorly differentiated lung adenocarcinoma and underwent
surgery. He presented a metastatic relapse 6 months after surgery treated with induction chemotherapy (platinum, pemetrexed and bevacizumab combination) followed by continuation maintenance (pemetrexed and bevacizumab combination) during 3 months. Because of disease progression, he received nivolumab, which is still ongoing with no adverse event. computed tomographyscan at 6 months showed a partial response. 4. Clinical case 4 A 42-year-old man received an AHSCT for a chronic lymphocytic leukaemia, with subsequent chronic cutaneous and digestive GVHD treated with steroids and ciclosporin. Six years later a scalp subcutaneous metastasis of melanoma, with no BRAF and NRAS mutations was resected. The primary melanoma could not be identified. One year later a cervical node was surgically resected and the patient was enrolled in an adjuvant clinical trial assessing the efficacy of pembrolizumab versus placebo. The treatment was stopped after 6 months because of disease progression. He received ipilimumab for four injections without efficacy and then started a second line of treatment with nivolumab. Two months after he was diagnosed with fulminant type 1 diabetes, nivolumab was maintained for 2 months despite this adverse event before a cerebral and systemic progression was observed. The patient died few weeks later.
140
A. Monneur et al. / European Journal of Cancer 81 (2017) 138e141
5. Discussion
References
Advances in AHSCT and supportive care have contributed to greater number of long-term survivors who remain free of their original disease [9]. However transplants recipients display a 2e3 fold higher risk of developing secondary solid malignancies compared with general population [10,11]. ICI have improved outcomes in advanced various solid malignancies including melanoma. Information about safety of ICI is essential for AHSCT recipients. Only few cases reporting efficacy and toxicity of ICI for solid organ transplant recipients have been published so far. Successful administration of ICI in liver and kidney transplant recipients without any toxicity has been described in the context of refractory melanoma [12e15]. Interestingly, one case of acute graft rejection has been described for a kidney transplant recipient receiving nivolumab after progression under ipilimumab for metastatic melanoma [16]. However, ICI management for organ transplant recipients remains poorly known [17]. To our knowledge, there is no such data in AHSCT recipients presenting subsequent solid tumours. Given the ability of ICI to activate T-cell, we could expect a GVHD reactivation, as it has been described in patients with relapsed haematological malignancies [18]. Despite that all our patients presented acute and chronic GVHD, there was no GVHD reactivation while they were no longer under immunosuppressive treatment. This may be explained by the delay between GVHD resolution and ICI initiation. One of our patients experienced fulminant type 1 diabetes, a rare adverse event described to be possibly related to auto-immune reaction [19]. It has been recently described in some patients receiving ICI, especially nivolumab, suggesting that T-cell activation could be involved in such phenomenon [20e22]. Moreover, one can also predict that ICI efficacy can be modified after AHSCT. Even though the small sample size does not allow any efficacy analysis, we observed that one patient among the four cases described here had a clinical benefit under nivolumab. This observation suggesting that ICI can be efficient after AHSCT obviously deserves to be confirmed in larger studies. Our data may be useful to clinicians who have to treat such patients.
[1] Robert C, Thomas L, Bondarenko I, O’Day S, Weber J, Garbe C, et al. Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. N Engl J Med 2011;364:2517e26. http: //dx.doi.org/10.1056/NEJMoa1104621. [2] Robert C, Schachter J, Long GV, Arance A, Grob JJ, Mortier L, et al. Pembrolizumab versus ipilimumab in advanced melanoma. N Engl J Med 2015;372:2521e32. http://dx.doi.org/10.1056/ NEJMoa1503093. [3] Hodi FS, O’Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 2010;363:711e23. http: //dx.doi.org/10.1056/NEJMoa1003466. [4] Brahmer J, Reckamp KL, Baas P, Crino` L, Eberhardt WEE, Poddubskaya E, et al. Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer. N Engl J Med 2015; 373:123e35. http://dx.doi.org/10.1056/NEJMoa1504627. [5] Borghaei H, Paz-Ares L, Horn L, Spigel DR, Steins M, Ready NE, et al. Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. N Engl J Med 2015;373: 1627e39. http://dx.doi.org/10.1056/NEJMoa1507643. [6] Reck M, Rodrı´guez-Abreu D, Robinson AG, Hui R, Cs} oszi T, Fu¨lo¨p A, et al. Pembrolizumab versus chemotherapy for PD-L1positive non-small-cell lung cancer. N Engl J Med 2016. http: //dx.doi.org/10.1056/NEJMoa1606774. [7] Lafage-Pochitaloff M, Costello R, Couez D, Simonetti J, Mannoni P, Mawas C, et al. Human CD28 and CTLA-4 Ig superfamily genes are located on chromosome 2 at bands q33-q34. Immunogenetics 1990;31:198e201. [8] Ishida Y, Agata Y, Shibahara K, Honjo T. Induced expression of PD-1, a novel member of the immunoglobulin gene superfamily, upon programmed cell death. EMBO J 1992;11:3887e95. [9] Gooley TA, Chien JW, Pergam SA, Hingorani S, Sorror ML, Boeckh M, et al. Reduced mortality after allogeneic hematopoieticcell transplantation. N Engl J Med 2010;363:2091e101. http: //dx.doi.org/10.1056/NEJMoa1004383. [10] Rizzo JD, Curtis RE, Socie´ G, Sobocinski KA, Gilbert E, Landgren O, et al. Solid cancers after allogeneic hematopoietic cell transplantation. Blood 2009;113:1175e83. http://dx.doi.org/10. 1182/blood-2008-05-158782. [11] Baker KS, DeFor TE, Burns LJ, Ramsay NKC, Neglia JP, Robison LL. New malignancies after blood or marrow stem-cell transplantation in children and adults: incidence and risk factors. J Clin Oncol Off J Am Soc Clin Oncol 2003;21:1352e8. http: //dx.doi.org/10.1200/JCO.2003.05.108. [12] Morales RE, Shoushtari AN, Walsh MM, Grewal P, Lipson EJ, Carvajal RD. Safety and efficacy of ipilimumab to treat advanced melanoma in the setting of liver transplantation. J Immunother Cancer 2015;3:22. http://dx.doi.org/10.1186/s40425-015-0066-0. [13] Lipson EJ, Bodell MA, Kraus ES, Sharfman WH. Successful administration of ipilimumab to two kidney transplantation patients with metastatic melanoma. J Clin Oncol Off J Am Soc Clin Oncol 2014;32:e69e71. http://dx.doi.org/10.1200/JCO.2013.49.2314. [14] Herz S, Ho¨fer T, Papapanagiotou M, Leyh JC, Meyenburg S, Schadendorf D, et al. Checkpoint inhibitors in chronic kidney failure and an organ transplant recipient. Eur J Cancer Oxf Engl 2016;67:66e72. http://dx.doi.org/10.1016/j.ejca.2016.07.026. 1990. [15] Ranganath HA, Panella TJ. Administration of ipilimumab to a liver transplant recipient with unresectable metastatic melanoma. J Immunother Hagerst Md 2015;38:211. http://dx.doi.org/10. 1097/CJI.0000000000000077. 1997. [16] Spain L, Higgins R, Gopalakrishnan K, Turajlic S, Gore M, Larkin J. Acute renal allograft rejection after immune checkpoint inhibitor therapy for metastatic melanoma. Ann Oncol Off J Eur Soc Med Oncol 2016;27:1135e7. http://dx.doi.org/10.1093/annonc/ mdw130.
Conflict of interest statement RS has received consulting fees from BMS. CGM has received consulting fees and travel grants from BMS. The other authors have no disclosure to declare. Funding This work has been funded by Institut Paoli-Calmettes and SIRIC (INCa-DGOSInserm 6038).
A. Monneur et al. / European Journal of Cancer 81 (2017) 138e141 [17] Maggiore U, Pascual J. The bad and the good news on cancer immunotherapy: implications for organ transplant recipients. Adv Chronic Kidney Dis 2016;23:312e6. http://dx.doi.org/10.1053/ j.ackd.2016.08.002. [18] Davids MS, Kim HT, Bachireddy P, Costello C, Liguori R, Savell A, et al. Ipilimumab for patients with relapse after allogeneic transplantation. N Engl J Med 2016;375:143e53. http: //dx.doi.org/10.1056/NEJMoa1601202. [19] Imagawa A, Hanafusa T. Pathogenesis of fulminant type 1 diabetes. Rev Diabet Stud RDS 2006;3:169e77. http://dx.doi.org/10. 1900/RDS.2006.3.169. [20] Okamoto M, Okamoto M, Gotoh K, Masaki T, Ozeki Y, Ando H, et al. Fulminant type 1 diabetes mellitus with anti-programmed
141
cell death-1 therapy. J Diabetes Investig 2016;7:915e8. http: //dx.doi.org/10.1111/jdi.12531. [21] Ishikawa K, Shono-Saito T, Yamate T, Kai Y, Sakai T, Shimizu F, et al. A case of fulminant type 1 diabetes mellitus, with a precipitous decrease in pancreatic volume, induced by nivolumab for malignant melanoma: analysis of HLA and CTLA-4 polymorphisms. Eur J Dermatol 2016. http://dx.doi.org/10.1684/ ejd.2016.2923. [22] Gaudy C, Cle´vy C, Monestier S, Dubois N, Pre´au Y, Mallet S, et al. Anti-PD1 pembrolizumab can induce exceptional fulminant type 1 diabetes. Diabetes Care 2015;38:e182e183. http://dx.doi.org/10. 2337/dc15-1331.