Letter to the Editor
Cryptogenic organizing pneumonia by alectinib
Neumonía organizada criptogenética por alectinib
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It is approved as a first-line drug for late-stage or metastatic non-small cell lung carcinoma with activity against ALK.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> The same is true of ceritinib, which has shown a reasonable safety profile, compared to other therapies. Pulmonary toxicity such as Cryptogenic organising pneumonia (COP) due to alectinib therapy is poorly documented worldwide.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">We analyse the case of an 85-year-old male with an excellent previous functional and cognitive situation, hypertensive with nephroangiosclerosis with a glomerular filtration rate of 65 mL/min. He has not smoked for 30 years, calculated as 20 Pack Years. Diagnosed with poorly differentiated lung carcinoma with focal squamous features stage III-A, with positive ALK immunohistochemical study, low PD-L1 expression, and undetected EGFR mutation. Oncospecific treatment with alectinib at a dose of 150 mg every 12 h was administered.</p><p id="par0015" class="elsevierStylePara elsevierViewall">Two weeks after the start of treatment, he began with progressive asthenia and dyspnea until it presented with minimal efforts, together with increased cough and expectoration, with haemoptoic and thicker sputum. Upon arrival at the A&E, he presented a fever peak of 38 °C. A chest X-ray was performed (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>), as well as a blood analysis showing creatinine: 1.62 mg/dL, leukocytes: 15,320/μl, 13,880 neutrophils, pO<span class="elsevierStyleInf">2</span>: 58 mmHg. He was admitted into hospital with a diagnosis of probable alectinib-induced pneumonitis. Alectinib was discontinued. Negative blood cultures. The diagnostic bronchoscopy showed moderate secretions in the bronchial systems and chronic signs of bronchitis. Bronchial aspirate culture: normal flora. After seven days of not administering alectinib, and with intensive glucocorticoid treatment + levofloxacin, a chest X-ray was repeated which showed a resolution of the pulmonary infiltrates. No changes to the basal treatment (amlodipine + lorazepam) was made. The transbronchial biopsy in the lingula report showed: histological findings suggestive of COP. At that time, we could not be sure whether the cause of COP was paraneoplastic or secondary to alectinib. The patient was discharged without respiratory failure, and a slow descending regimen of glucocorticoids. As an oncological response to alectinib had been observed, it was decided to reintroduce it one week after discharge.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">Seven days after the reintroduction of alectinib, the patient visited the A&E due to a fever peak of 39 °C, without increased dyspnea or respiratory failure. The chest X-ray was unchanged from the previous one. At 24 h, alectinib was reintroduced, after it had been suspended in the emergency room. Three days later, the patient again presented dyspnea and partial respiratory failure. A chest X-ray was repeated confirming the presence of new bilateral patchy cotton-like infiltrates. It was then decided to stop alectinib treatment indefinitely. Over the next 72 h, the patient presented clinical and radiological improvement. Treatment with ceritinib was started, with good tolerance to the same, after one month of administration.</p><p id="par0025" class="elsevierStylePara elsevierViewall">To evaluate the causal relationship between alectinib and pulmonary-type adverse drug reaction (ADR), we used the Naranjo algorithm. The results showed that the ADR was probable-definitive due to taking alectinib, and the probability was doubtful that it was related to the tumour, or to other substances, taking into account the clinical response to drug withdrawal.</p><p id="par0030" class="elsevierStylePara elsevierViewall">COP is a clinicopathological syndrome characterised by an excessive proliferation of granulation tissue, forming plugs inside the small airways and alveoli, associated with a chronic inflammatory cellular infiltrate around them. A common pathological finding is the existence of a pattern of organised pneumonia in the periphery of a bronchogenic carcinoma. But the coexistence of a bronchogenic carcinoma and a COP in lung areas that are topographically distant lung is exceptional.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">In the follow-up of a patient with lung carcinoma, the appearance of radiological alterations in the form of nodules, masses or infiltrates is usually related to the appearance of an infectious process or with progression of the neoplastic disease, but the differential diagnosis must also consider the possibility of a COP, both of iatrogenic and paraneoplastic aetiology. With adequate treatment, or with the suspension of the aetiological drug, this pathology can have a good prognosis.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Funding</span><p id="par0040" class="elsevierStylePara elsevierViewall">This work has not received any type of funding.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Conflict of interests</span><p id="par0045" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflict of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Funding" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Conflict of interests" ] 2 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: López Pardo P, Sánchez Peña AM, Río Ramírez MT. Neumonía organizada criptogenética por alectinib. Med Clin (Barc). 2021;157:93–94.</p>" ] ] "multimedia" => array:1 [ 0 => array:8 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1233 "Ancho" => 1500 "Tamanyo" => 138519 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">PA chest X-ray in supine position on his first arrival at the A&E.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:5 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Alectinib for ALK-positive non-small-cell lung cancer" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "A. 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