Letter to the Editor
Immunotherapy rechallenge in patients with non-small-cell lung cancer
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España, I. Guasch, E. Carcereny" "autores" => array:3 [ 0 => array:4 [ "nombre" => "S." "apellidos" => "España" "email" => array:1 [ 0 => "sofia.ef@iconcologia.net" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "I." "apellidos" => "Guasch" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "E." "apellidos" => "Carcereny" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Medical Oncology Service. Catalan Institute of Oncology, Badalona, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Radiodiagnostic Service, Hospital Germans Trias i Pujol, Badalona, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 706 "Ancho" => 1600 "Tamanyo" => 83739 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">A. Postero anterior chest radiograph shows air space consolidation of rigth upper lobule with lung volume decrease (radiotherapy fibrosis). B. Postero anterior chest radiograph shows new heterogeneous bilateral air space opacities.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Immunotherapy is an effective treatment option for patients with non-small-cell lung cancer (NSCLC) with advanced disease. Several immune checkpoint inhibitors (ICI) have significantly improved survival of patients with NSCLC.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">1</span></a> The safety profile of immunotherapy differs from the known safety profile of chemotherapy and includes immune-related adverse events (irAEs) such as fatigue, rash, pruritus, diarrhea and arthralgia, occurring in >20% of patients.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">2</span></a> A recent meta-analysis reported all-grade immune-related lung toxicity (pneumonitis) in 4.1% of patients with NSCLC treated with ICIs, which was reported as grade ≥3 in 1.8% of patients.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">3</span></a> In daily practice, it is important to know whether it is possible to rechallenge a patient with NSCLC with the same PD-1 inhibitor after resolution of an irAE to be able to continue providing clinical benefit.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Case presentation</span><p id="par0010" class="elsevierStylePara elsevierViewall">We report the case of a 63-year-old female patient diagnosed in December 2014 with NSCLC (cT2N2M0), localized at the right upper lobe. She received neoadjuvant chemoradiotherapy with intravenous cisplatin 75<span class="elsevierStyleHsp" style=""></span>mg/m<span class="elsevierStyleSup">2</span> plus vinorelbine 25<span class="elsevierStyleHsp" style=""></span>mg/m<span class="elsevierStyleSup">2</span> on days 1 and 8 in 3-week cycles and 60<span class="elsevierStyleHsp" style=""></span>Gy (in 2<span class="elsevierStyleHsp" style=""></span>Gy per fraction) from January 2015 until April 2015. After completing 2 cycles she was not a candidate for surgery due to the persistence of N2 (evaluated by Endobronchial Ultrasonography [EBUS]), so she continued with 2 more cycles of chemoradiotherapy until May 2015. In January 2016, the patient showed disease progression in the lung (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>A), so she started a second-line of treatment with nivolumab (3<span class="elsevierStyleHsp" style=""></span>mg/kg intravenously every 14 days) attaining a partial response in March 2016 after 4 treatment cycles. In April 2016, the patient was admitted with grade 3 fever and increased dyspnea that occurred even on minimal exertion. These symptoms had been ongoing for 2 weeks before being admitted to the hospital. An X-ray was performed, showing bilateral dispersed alveolar opacities (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>B). The main differential diagnoses were infection, immune-related toxicity, radiation-induced pneumonitis, and disease progression. Thoracic computed tomography (CT) (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>A), bronchoscopy with bronchoalveolar lavage (BAL) and bronchoalveolar aspirate (BAS) were performed to ensure the correct diagnosis. Negative bacterial cultures ruled out the possibility of infection and cytology did not show malignant cells. Although late radiation pneumonitis was difficult to exclude, the time elapsed between the end of the radiotherapy treatment and the beginning of the symptoms suggested an immunerelated pneumonitis. Moreover, irradiated lungs are more susceptible to develop pneumonitis when treated with ICI. The patient was diagnosed with a grade 3 immune-related pneumonitis and the PD-1 inhibitor had to be permanently stopped, despite having attained a partial response. Pneumonitis was treated with high doses of corticosteroids (methylprednisolone 1<span class="elsevierStyleHsp" style=""></span>mg/kg/day) followed by tapering. Patient symptoms improved after 1 week of corticosteroid treatment, with complete clinical and radiological recovery after 11 weeks of treatment (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>B). On May 2017, during a follow-up visit, a thoracic CT scan showed disease progression. Considering the patient's previous response to immunotherapy, including 14 months of stable disease after stopping treatment, nivolumab rechallenge was proposed as a treatment option despite the toxicity reported. To avoid new irAEs, nivolumab (3<span class="elsevierStyleHsp" style=""></span>mg/kg intravenously every 14 days) was reinitiated along with low dose corticosteroids (methylprednisolone 8<span class="elsevierStyleHsp" style=""></span>mg/day). After four cycles, the patient achieved a partial response in the lung tumor with no further lung toxicity.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Discussion</span><p id="par0015" class="elsevierStylePara elsevierViewall">Immunotherapy-related lung toxicity is rare but can be life-threatening.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">2</span></a> The clinical presentation of pneumonitis usually consists of non-specific symptoms. However, it is essential to consider pneumonitis among the differential diagnoses in patients receiving treatment with PD-1 or PD-L1 inhibitors, before the respiratory function worsens.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">3</span></a> To correctly diagnose pneumonitis, a bronchoscopy must be performed to rule out other etiologies, such as infection. The main treatment for the irAE of pneumonia is the administration of high doses of corticosteroids (1–1.5<span class="elsevierStyleHsp" style=""></span>mg/kg) with subsequent tapering when symptoms and radiological imaging show improvement.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">4</span></a> Moreover, according to the evidence described in the literature,<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">4,5</span></a> permanent cessation of immunotherapy is the standard procedure in a patient experiencing a grade 3–4 irAE. However, clinicians should always consider the potential loss of clinical benefit for patients in these situations. Although the experience described in our patient reflects a single case, other case series have shown that rechallenging with a PD-1 inhibitor could be an option for patients with NSCLC, even after discontinuation due to toxicity.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">6</span></a> Currently, a few trials, such as the REPLAY study (<a href="ctgov:NCT03526887">NCT03526887</a>) carried out by the Spanish Lung Cancer Group, are evaluating pembrolizumab in NSCLC that had failed after obtaining benefit from a checkpoint inhibitor. Furthermore, other studies are assessing the risk of recall toxicities when restarting immunotherapy. A study of patients who have been diagnosed with immune-related pneumonitis showed that 25% of these patients experienced a recurrence when rechallenged with PD-1/PD-L1 inhibitor.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">7</span></a> In summary, ICI rechallenge in patients with NSCLC who experienced a grade 3–4 irAE could be an option, although more evidence is needed.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Case presentation" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Discussion" ] 2 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "multimedia" => array:2 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 706 "Ancho" => 1600 "Tamanyo" => 83739 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">A. Postero anterior chest radiograph shows air space consolidation of rigth upper lobule with lung volume decrease (radiotherapy fibrosis). B. Postero anterior chest radiograph shows new heterogeneous bilateral air space opacities.</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 612 "Ancho" => 1600 "Tamanyo" => 135044 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A. CT scan (lung window) shows multiple peripheral poorly defined areas of focal consolidation, very suggestive or organizing penumonia. B. CT scan (lung window), three month later shows resolution of peripheral areas of focal consolidation, but persistence of parahilar consolidation because of radiation fibrosis. Note the bronchiectasis and volume loss and the sharp demarcation between normal lung tissue and areas of fibrosis.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:7 [ 0 => array:3 [ "identificador" => "bib0040" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Immunotherapy in non-small cell lung cancer: facts and hopes" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "D.B. Doroshow" 1 => "M.F. Sanmamed" 2 => "K. Hastings" 3 => "K. Politi" 4 => "D.L. Rimm" 5 => "L. Chen" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1158/1078-0432.CCR-18-1538" "Revista" => array:6 [ "tituloSerie" => "Clin Cancer Res" "fecha" => "2019" "volumen" => "25" "paginaInicial" => "4592" "paginaFinal" => "4602" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30824587" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0045" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Diagnosis, monitoring and management of immune-related adverse drug reactions of anti-PD-1 antibody therapy" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "T.K. Eigentler" 1 => "J.C. Hassel" 2 => "C. Berking" 3 => "J. Aberle" 4 => "O. Bachmann" 5 => "V. Grunwald" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.ctrv.2016.02.003" "Revista" => array:6 [ "tituloSerie" => "Cancer Treat Rev" "fecha" => "2016" "volumen" => "45" "paginaInicial" => "7" "paginaFinal" => "18" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26922661" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0050" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Incidence of programmed cell death 1 inhibitor-related pneumonitis in patients with advanced cancer: a systematic review and meta-analysis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "M. Nishino" 1 => "A. Giobbie-Hurder" 2 => "H. Hatabu" 3 => "N.H. Ramaiya" 4 => "F.S. Hodi" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1001/jamaoncol.2016.2453" "Revista" => array:7 [ "tituloSerie" => "JAMA Oncol" "fecha" => "2016" "volumen" => "2" "numero" => "12" "paginaInicial" => "1607" "paginaFinal" => "1616" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27540850" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0055" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Management of toxicities from immunotherapy: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J. Haanen" 1 => "F. Carbonnel" 2 => "C. Robert" 3 => "K.M. Kerr" 4 => "S. Peters" 5 => "J. Larkin" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/annonc/mdx225" "Revista" => array:7 [ "tituloSerie" => "Ann Oncol" "fecha" => "2017" "volumen" => "28" "numero" => "Suppl_4" "paginaInicial" => "iv119" "paginaFinal" => "iv142" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28881921" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0060" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Management of immune checkpoint blockade dysimmune toxicities: a collaborative position paper" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S. Champiat" 1 => "O. Lambotte" 2 => "E. Barreau" 3 => "R. Belkhir" 4 => "A. Berdelou" 5 => "F. Carbonnel" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/annonc/mdv623" "Revista" => array:6 [ "tituloSerie" => "Ann Oncol" "fecha" => "2016" "volumen" => "27" "paginaInicial" => "559" "paginaFinal" => "574" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26715621" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0065" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Immune checkpoint inhibitor re-challenge in patients with advanced non-small cell lung cancer" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Niki" 1 => "A. Nakaya" 2 => "T. Kurata" 3 => "H. Yoshioka" 4 => "T. Kaneda" 5 => "K. Kibata" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.18632/oncotarget.25949" "Revista" => array:6 [ "tituloSerie" => "Oncotarget" "fecha" => "2018" "volumen" => "9" "paginaInicial" => "32298" "paginaFinal" => "32304" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30190787" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0070" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Pneumonitis in patients treated with anti-programmed death-1/programmed death ligand 1 therapy" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J. Naidoo" 1 => "X. Wang" 2 => "K.M. Woo" 3 => "T. Iyriboz" 4 => "D. Halpenny" 5 => "J. Cunningham" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1200/JCO.2016.68.2005" "Revista" => array:6 [ "tituloSerie" => "J Clin Oncol" "fecha" => "2017" "volumen" => "35" "paginaInicial" => "709" "paginaFinal" => "717" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27646942" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/25310437/0000002600000004/v2_202009030742/S2531043720300295/v2_202009030742/en/main.assets" "Apartado" => array:4 [ "identificador" => "72880" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Letters to the Editor" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/25310437/0000002600000004/v2_202009030742/S2531043720300295/v2_202009030742/en/main.pdf?idApp=UINPBA00004E&text.app=https://journalpulmonology.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2531043720300295?idApp=UINPBA00004E" ]
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| 2023 September | 45 | 34 | 79 |
| 2023 August | 48 | 26 | 74 |
| 2023 July | 46 | 33 | 79 |
| 2023 June | 33 | 17 | 50 |
| 2023 May | 61 | 27 | 88 |
| 2023 April | 80 | 18 | 98 |
| 2023 March | 123 | 21 | 144 |
| 2023 February | 61 | 26 | 87 |
| 2023 January | 51 | 24 | 75 |
| 2022 December | 93 | 36 | 129 |
| 2022 November | 89 | 36 | 125 |
| 2022 October | 137 | 41 | 178 |
| 2022 September | 83 | 51 | 134 |
| 2022 August | 102 | 36 | 138 |
| 2022 July | 119 | 52 | 171 |
| 2022 June | 74 | 30 | 104 |
| 2022 May | 90 | 37 | 127 |
| 2022 April | 77 | 37 | 114 |
| 2022 March | 101 | 45 | 146 |
| 2022 February | 84 | 50 | 134 |
| 2022 January | 64 | 59 | 123 |
| 2021 December | 73 | 39 | 112 |
| 2021 November | 70 | 44 | 114 |
| 2021 October | 51 | 52 | 103 |
| 2021 September | 80 | 47 | 127 |
| 2021 August | 55 | 56 | 111 |
| 2021 July | 44 | 26 | 70 |
| 2021 June | 72 | 31 | 103 |
| 2021 May | 71 | 50 | 121 |
| 2021 April | 226 | 124 | 350 |
| 2021 March | 150 | 56 | 206 |
| 2021 February | 107 | 43 | 150 |
| 2021 January | 76 | 36 | 112 |
| 2020 December | 99 | 61 | 160 |
| 2020 November | 79 | 28 | 107 |
| 2020 October | 87 | 37 | 124 |
| 2020 September | 87 | 55 | 142 |
| 2020 August | 148 | 65 | 213 |
| 2020 July | 162 | 111 | 273 |
| 2020 June | 76 | 31 | 107 |
| 2020 May | 68 | 31 | 99 |
| 2020 April | 4 | 4 | 8 |
Show all
