Safety of brigatinib following alectinib-induced-pneumonitis: Case report

Safety of brigatinib following alectinib-induced-pneumonitis: Case report | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Safety of brigatinib following alectinib-induced-pneumonitis: Case report Blerina Resuli, Heidi Galarza, Elsner Laura, Diego Kauffmann-Guerrero, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4650153/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Anaplastic lymphoma kinase tyrosine kinase inhibitors (ALK TKIs) show robust activity in patients with non-small-cell lung cancer (NSCLC) harboring an ALK-rearrangement. Rare but serious side effects, such as pneumonitis can occur with ALK TKIs. We here report a case of a patient with NSCLC with echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4- ALK) translocation who tolerated brigatinib following alectinib-induced pneumonitis. The patient was notable for diffuse ground-glass opacities 2 months after of initiating alectinib without dyspnea and hypoxemia. With no alternative etiology of pneumonitis identified, the patient was treated with corticosteroids and discontinuation of alectinib. Following rapid clinical recovery and radiographic resolution of the opacities, the patient was started with brigatinib, with no recurrence of the clinical symptoms or radiographic findings of pneumonitis. While further descriptions are needed, our experience suggests that switching to a second ALK-TKI such as brigatinib may be a safe therapeutic option in some patients who develop drug-induced pneumonitis on alectinib. alectinib brigatinib NSCLC pneumonitis case report Figures Figure 1 Figure 2 Introduction Anaplastic lymphoma kinase (ALK) inhibitors for oncogenic ALK gene rearranged non-small cell lung cancer (NSCLC), noted in 3.6–4.4% of patients with NSCLC [ 1 ]. ALK TKIs have changed the treatment paradigm and improved the prognosis of oncogenic addicted NSCLC patients [ 2 ]. However adverse events (AEs) associated with ALK TKIs inevitably occur and cannot be ignored. The incidence of serious adverse events (SAEs) ranges from 27.1 to 45.7% in patients receiving treatment with ALK TKIs [ 3 ]. Among these SAEs, pneumonitis is a rare but hazard AE that can be life threating and its incidence has gradually increased in recent years. The incidence of pneumonitis in current data varies from 0.4–0.9% among different studies [ 4 ]. Timely diagnosis of ALK-TKIs are key to improving the prognosis of these patients. However, no reports were available regarding the utility of switching to brigatinib after alectinib-induced pneumonitis. Here we report a case of a patient with NSCLC EML4-ALK translocation with safely tolerated brigatinib following alectinib-induced pneumonitis. Case Presentation A 65-year-old Caucasian, never smoker women with a history of bipolar disorder in medical treatment with lithium was diagnosed in December 2022 with a mass in the left superior lung measuring > 4 cm with invasion of mediastinum and satellite nodules in the same lobe. Positron Emission Tomography/Computed Tomography (PET/CT) scan showed additional hypermetabolic activity of the lung lesion as well as in the contralateral lung and right hilar and mediastinal lymph nodes. Magnetic resonance image (MRI) of the brain revealed a frontal lesion measuring 4,1 x 4,9 cm concerning for metastasis. Biopsy of the lung mass was consistent with a TTF1 positive, lung adenocarcinoma with a tumor proportion score of programmed death-ligand 1 (PD-L1) of 3%. Next-generation sequencing (NGS) revealed an EML4-ALK fusion. In January 2023 following the diagnosis of stage IV (cT4cN3cM1c) ALK-rearranged NSCLC the patient was started first-line alectinib 600 mg twice daily. After 2 months of alectinib treatment the patient reported dyspnea and chest pain and diffuse ground-glass opacities were found in the CT scan of the chest (Fig. 1 ). Sputum was negative for bacterial infection. Alectinib was discontinued at this time and the patient initiated Prednisolone 1 mg/kg/daily for grade 2 pneumonitis. Within 48 hours, the patient ‘s clinical condition rapidly improved. Three weeks after initiating steroids a repeat CT scan of the chest showed that the ground-glass opacities had almost completely resolved without evidence of short-term tumor progression (Fig. 2 ). MRI of the brain revealed a partial response. The patient was then started on brigatinib 90 mg daily for the first 7 days (beginning April 2023) and then increased to 180 mg once daily. Brigatinib was well tolerated, and the patient has thus far remained on brigatinib for > 9 months without clinical or radiographic evidence of pneumonitis. In January 2024 a CT scan of the chest and abdomen as well as the MRI of the brain revealed progression in the lung and lymph nodes and new lesions in the brain. In February 2024 following a careful discussion of the potential risks and alternative, the started lorlatinib 100 mg daily. She developed asymptomatic hyperlipidemia managed with statins without lorlatinib dose reduction. Under lorlatinib the patient did not develop any central nervous system (CNS) effects, despite the previous diagnosis of bipolar disorder. Lithium treatment and psychiatric monitoring were continued. Discussion To our knowledge, the safety of brigatinib in patients with a history of pneumonitis on other TKISTiasnot been previously reported. Although the incidence of pneumonitis is low, it can be life threatening and is incidence has gradually increased in recent years. Currently available data regarding the incidence of pneumonitis do not seem conclusive. The incidence of pneumonitis varies from 0,4% to 0,9% among different studies [ 4 , 5 ]. Once pneumonitis occurs, dose reduction, treatment suspension or medication discontinuation is required, which cab adversely affect OS and curative intention. Timely diagnosis and early treatment of pneumonitis caused by ALK-TIs are key to improving the prognosis of these patients. Alternative ALK TKIs are commonly used in clinical practice as different ALK TKIs may have different mechanisms for the development of pneumonitis [ 8 ]. Because of the mortality associated with drug-induced pneumonitis the question to whether or not to restart ALK targeted therapy in patients who have a history of pneumonitis requires careful consideration. A Limited number of previous case reports have described the successful of crizotinib, ceritinib, alectinib or brigatinib in patients with ALK-rearranged NSCLC who have recovered from pneumonitis secondary to ALK-TKIs [ 6 , 7 , 9 , 10 ]. In some of these cases patients resumed ALK-TKI after having mild pneumonitis. In comparison our patient, developed acute pneumonitis under alectinib and the subsequent tolerance on brigatinib was notable. Lorlatinib would have been an alternative choice for the treatment after alectinib, however; in light of the patient’s psychiatric history and possible psychiatric side effects of lorlatinib, we chose brigatinib. It is reassuring that the subsequent treatment with lorlatinib did not cause psychiatric deterioration. Conclusion We describe a case of well tolerated brigatinib after alectinib-induced pneumonitis. Further research is needed to determine whether re-challenging with ALK TKIs carries an increased risk of recurrent pneumonitis. However, caution and close monitoring must be employed when considering this approach in clinical practice. Declarations Author Contribution B.R and H.G wrote the main manuscript textE.L. prepared figures 1-2All authors review and approved the manuscript Acknowledgement – The patient involved in this case report gave her informed consent authorizing use and disclosure of her health information. Data availability: The authors confirm that the data supporting the findings of this study are available within the article. Raw data that support the findings of this study are available from the corresponding author, upon reasonable request. Disclosure Statement of Conflict of Interest: All authors declare no conflict of interest. Ethics statement: The study was conducted in accordance with the guideline form the ethic committee of the LMU University Hospital in Munich and it was conducted in accordance with the Declaration of Helsinki. References Duyster J, Bai RY, Morris SW. Translocations involving anaplastic lymphoma kinase (ALK). Oncogene. 2001;20:5623–37. Mok T, Camidge DR, Gadgeel SM, et al. Updated overall survival and final progression-free survival with treatment-naive advanced ALK-positive non-small cell lung cancer in the ALEX study. Ann Oncol. 2020;31(8):1056–64. Shaw AT, Yeap BY, Mino-Kenudson M, et al. Clinical features and outcome of patients with non‐small‐cell lung cancer who harbor EML4‐ALK. J Clin Oncol. 2009;27:4247–53. Yoneda KY, Scranton JR, Cadogan MA, et al. Interstitial lung disease associated with Crizotinib in patients with advanced non-small cell lung cancer: indipendent review of four PROFILE trials. Clin Lung Cancer. 2017;18(5):472–9. Suh CH, Kim KW, Pyo J, et al. The incidence of ALK inhibitor-related pneumonitis in advanced non-small cell lung cancer patients: A systemic review and meta-analysis. Lung Cancer. 2019;132:79–86. Domènech M, Jovè M, Marin M, Nadal E. Successful treatment of brigatinib in a patient with ALK-rearranged lung adenocarcinoma who developed crizotinib-induced interstitial lung disease. Lung Cancer. 2018;119:99–102. Myall NJ, Lei AQ, Wakelee HA. Safety of lorlatinib following alectinib-induced penumonitis in two patients with ALK-rearranged non-small cell lung cancer: a case series. Transl Lung Cancer Res. 2021;10(1):487–95. Loong HH, Mok K, Leung LKS, Mok TSK. Crizotinib in the managment of advanced-stage non-small-cell lung cancer. Future Oncol. 2015;11(5):735–45. Hwang A, Iskandar A, Dasanu C. Successful reintroduction of alectinib after inducing interstitial lung disease in a patients with lung cancer. J Oncol Pharm Pract. 2019;25:1531–3. Asai N, Yokoi T, Yamaguchi E, et al. Successful crizotinib rechallenge after crizotinib-induced organizing pneumonia in anaplastic lymphoma kinase-rearranged non-small cell lung cancer. Case Rep Oncol. 2014;7:681–4. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4650153","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":334722750,"identity":"9caa2cd5-7a36-4b93-bb0b-ad2ecebde0ba","order_by":0,"name":"Blerina 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opacities involving the entirety of both lung fields.\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-4650153/v1/e083f7fe1ad43e2e9302ee02.jpeg"},{"id":62156103,"identity":"2056a401-806d-460e-b773-a26773498f78","added_by":"auto","created_at":"2024-08-09 21:07:52","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":421332,"visible":true,"origin":"","legend":"\u003cp\u003eCT images of the chest after 3 weeks while the patient remained on corticosteroids and off alectinib, the previously ground-glass opacities were resolved\u003c/p\u003e","description":"","filename":"floatimage2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-4650153/v1/3f874b438cd94105dbd5365c.jpeg"},{"id":64660481,"identity":"010fe446-1c49-4e76-810e-da99072451a5","added_by":"auto","created_at":"2024-09-17 07:47:25","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":969250,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4650153/v1/e5a1f727-8706-4552-8f97-03884db487e1.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Safety of brigatinib following alectinib-induced-pneumonitis: Case report","fulltext":[{"header":"Introduction","content":"\u003cp\u003eAnaplastic lymphoma kinase (ALK) inhibitors for oncogenic ALK gene rearranged non-small cell lung cancer (NSCLC), noted in 3.6\u0026ndash;4.4% of patients with NSCLC [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. ALK TKIs have changed the treatment paradigm and improved the prognosis of oncogenic addicted NSCLC patients [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eHowever adverse events (AEs) associated with ALK TKIs inevitably occur and cannot be ignored. The incidence of serious adverse events (SAEs) ranges from 27.1 to 45.7% in patients receiving treatment with ALK TKIs [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Among these SAEs, pneumonitis is a rare but hazard AE that can be life threating and its incidence has gradually increased in recent years. The incidence of pneumonitis in current data varies from 0.4\u0026ndash;0.9% among different studies [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Timely diagnosis of ALK-TKIs are key to improving the prognosis of these patients. However, no reports were available regarding the utility of switching to brigatinib after alectinib-induced pneumonitis. Here we report a case of a patient with NSCLC EML4-ALK translocation with safely tolerated brigatinib following alectinib-induced pneumonitis.\u003c/p\u003e"},{"header":"Case Presentation","content":"\u003cp\u003eA 65-year-old Caucasian, never smoker women with a history of bipolar disorder in medical treatment with lithium was diagnosed in December 2022 with a mass in the left superior lung measuring\u0026thinsp;\u0026gt;\u0026thinsp;4 cm with invasion of mediastinum and satellite nodules in the same lobe. Positron Emission Tomography/Computed Tomography (PET/CT) scan showed additional hypermetabolic activity of the lung lesion as well as in the contralateral lung and right hilar and mediastinal lymph nodes. Magnetic resonance image (MRI) of the brain revealed a frontal lesion measuring 4,1 x 4,9 cm concerning for metastasis. Biopsy of the lung mass was consistent with a TTF1 positive, lung adenocarcinoma with a tumor proportion score of programmed death-ligand 1 (PD-L1) of 3%. Next-generation sequencing (NGS) revealed an EML4-ALK fusion.\u003c/p\u003e \u003cp\u003eIn January 2023 following the diagnosis of stage IV (cT4cN3cM1c) ALK-rearranged NSCLC the patient was started first-line alectinib 600 mg twice daily. After 2 months of alectinib treatment the patient reported dyspnea and chest pain and diffuse ground-glass opacities were found in the CT scan of the chest (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Sputum was negative for bacterial infection. Alectinib was discontinued at this time and the patient initiated Prednisolone 1 mg/kg/daily for grade 2 pneumonitis. Within 48 hours, the patient \u0026lsquo;s clinical condition rapidly improved. Three weeks after initiating steroids a repeat CT scan of the chest showed that the ground-glass opacities had almost completely resolved without evidence of short-term tumor progression (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). MRI of the brain revealed a partial response.\u003c/p\u003e \u003cp\u003eThe patient was then started on brigatinib 90 mg daily for the first 7 days (beginning April 2023) and then increased to 180 mg once daily. Brigatinib was well tolerated, and the patient has thus far remained on brigatinib for \u0026gt;\u0026thinsp;9 months without clinical or radiographic evidence of pneumonitis.\u003c/p\u003e \u003cp\u003eIn January 2024 a CT scan of the chest and abdomen as well as the MRI of the brain revealed progression in the lung and lymph nodes and new lesions in the brain. In February 2024 following a careful discussion of the potential risks and alternative, the started lorlatinib 100 mg daily. She developed asymptomatic hyperlipidemia managed with statins without lorlatinib dose reduction. Under lorlatinib the patient did not develop any central nervous system (CNS) effects, despite the previous diagnosis of bipolar disorder. Lithium treatment and psychiatric monitoring were continued.\u003c/p\u003e "},{"header":"Discussion","content":"\u003cp\u003eTo our knowledge, the safety of brigatinib in patients with a history of pneumonitis on other TKISTiasnot been previously reported. Although the incidence of pneumonitis is low, it can be life threatening and is incidence has gradually increased in recent years. Currently available data regarding the incidence of pneumonitis do not seem conclusive. The incidence of pneumonitis varies from 0,4% to 0,9% among different studies [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Once pneumonitis occurs, dose reduction, treatment suspension or medication discontinuation is required, which cab adversely affect OS and curative intention. Timely diagnosis and early treatment of pneumonitis caused by ALK-TIs are key to improving the prognosis of these patients. Alternative ALK TKIs are commonly used in clinical practice as different ALK TKIs may have different mechanisms for the development of pneumonitis [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eBecause of the mortality associated with drug-induced pneumonitis the question to whether or not to restart ALK targeted therapy in patients who have a history of pneumonitis requires careful consideration. A Limited number of previous case reports have described the successful of crizotinib, ceritinib, alectinib or brigatinib in patients with ALK-rearranged NSCLC who have recovered from pneumonitis secondary to ALK-TKIs [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. In some of these cases patients resumed ALK-TKI after having mild pneumonitis. In comparison our patient, developed acute pneumonitis under alectinib and the subsequent tolerance on brigatinib was notable. Lorlatinib would have been an alternative choice for the treatment after alectinib, however; in light of the patient’s psychiatric history and possible psychiatric side effects of lorlatinib, we chose brigatinib. It is reassuring that the subsequent treatment with lorlatinib did not cause psychiatric deterioration.\u003c/p\u003e "},{"header":"Conclusion","content":"\u003cp\u003eWe describe a case of well tolerated brigatinib after alectinib-induced pneumonitis. Further research is needed to determine whether re-challenging with ALK TKIs carries an increased risk of recurrent pneumonitis. However, caution and close monitoring must be employed when considering this approach in clinical practice.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eB.R and H.G wrote the main manuscript textE.L. prepared figures 1-2All authors review and approved the manuscript\u003c/p\u003e\u003ch2\u003eAcknowledgement \u0026ndash;\u003c/h2\u003e \u003cp\u003e The patient involved in this case report gave her informed consent authorizing use and disclosure of her health information.\u003c/p\u003e\u003ch2\u003eData availability:\u003c/h2\u003e \u003cp\u003eThe authors confirm that the data supporting the findings of this study are available within the article. Raw data that support the findings of this study are available from the corresponding author, upon reasonable request.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eDisclosure Statement of Conflict of Interest: All authors declare no conflict of interest.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEthics statement: The study was conducted in accordance with the guideline form the ethic committee of the LMU University Hospital in Munich and it was conducted in accordance with the Declaration of Helsinki. \u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eDuyster J, Bai RY, Morris SW. Translocations involving anaplastic lymphoma kinase (ALK). Oncogene. 2001;20:5623\u0026ndash;37.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMok T, Camidge DR, Gadgeel SM, et al. Updated overall survival and final progression-free survival with treatment-naive advanced ALK-positive non-small cell lung cancer in the ALEX study. Ann Oncol. 2020;31(8):1056\u0026ndash;64.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShaw AT, Yeap BY, Mino-Kenudson M, et al. Clinical features and outcome of patients with non‐small‐cell lung cancer who harbor EML4‐ALK. J Clin Oncol. 2009;27:4247\u0026ndash;53.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYoneda KY, Scranton JR, Cadogan MA, et al. Interstitial lung disease associated with Crizotinib in patients with advanced non-small cell lung cancer: indipendent review of four PROFILE trials. Clin Lung Cancer. 2017;18(5):472\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSuh CH, Kim KW, Pyo J, et al. The incidence of ALK inhibitor-related pneumonitis in advanced non-small cell lung cancer patients: A systemic review and meta-analysis. Lung Cancer. 2019;132:79\u0026ndash;86.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDom\u0026egrave;nech M, Jov\u0026egrave; M, Marin M, Nadal E. Successful treatment of brigatinib in a patient with ALK-rearranged lung adenocarcinoma who developed crizotinib-induced interstitial lung disease. Lung Cancer. 2018;119:99\u0026ndash;102.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMyall NJ, Lei AQ, Wakelee HA. Safety of lorlatinib following alectinib-induced penumonitis in two patients with ALK-rearranged non-small cell lung cancer: a case series. Transl Lung Cancer Res. 2021;10(1):487\u0026ndash;95.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLoong HH, Mok K, Leung LKS, Mok TSK. Crizotinib in the managment of advanced-stage non-small-cell lung cancer. Future Oncol. 2015;11(5):735\u0026ndash;45.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHwang A, Iskandar A, Dasanu C. Successful reintroduction of alectinib after inducing interstitial lung disease in a patients with lung cancer. J Oncol Pharm Pract. 2019;25:1531\u0026ndash;3.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAsai N, Yokoi T, Yamaguchi E, et al. Successful crizotinib rechallenge after crizotinib-induced organizing pneumonia in anaplastic lymphoma kinase-rearranged non-small cell lung cancer. Case Rep Oncol. 2014;7:681\u0026ndash;4.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"alectinib, brigatinib, NSCLC, pneumonitis, case report","lastPublishedDoi":"10.21203/rs.3.rs-4650153/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4650153/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eAnaplastic lymphoma kinase tyrosine kinase inhibitors (ALK TKIs) show robust activity in patients with non-small-cell lung cancer (NSCLC) harboring an ALK-rearrangement. Rare but serious side effects, such as pneumonitis can occur with ALK TKIs.\u003c/p\u003e \u003cp\u003eWe here report a case of a patient with NSCLC with echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4- ALK) translocation who tolerated brigatinib following alectinib-induced pneumonitis. The patient was notable for diffuse ground-glass opacities 2 months after of initiating alectinib without dyspnea and hypoxemia. With no alternative etiology of pneumonitis identified, the patient was treated with corticosteroids and discontinuation of alectinib. Following rapid clinical recovery and radiographic resolution of the opacities, the patient was started with brigatinib, with no recurrence of the clinical symptoms or radiographic findings of pneumonitis. While further descriptions are needed, our experience suggests that switching to a second ALK-TKI such as brigatinib may be a safe therapeutic option in some patients who develop drug-induced pneumonitis on alectinib.\u003c/p\u003e","manuscriptTitle":"Safety of brigatinib following alectinib-induced-pneumonitis: Case report","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-08-09 21:07:48","doi":"10.21203/rs.3.rs-4650153/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"f61bf0bd-e0ab-4332-ac80-6e1a0eab3889","owner":[],"postedDate":"August 9th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-09-17T07:39:19+00:00","versionOfRecord":[],"versionCreatedAt":"2024-08-09 21:07:48","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4650153","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4650153","identity":"rs-4650153","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}