Organizing pneumonia in ALK+ lung adenocarcinoma treated with ceritinib: A case report and literature review

Medicine (Baltimore). 2021 Jul 2;100(26):e26449. doi: 10.1097/MD.0000000000026449.

Abstract

Rationale: Anaplastic lymphoma kinase (ALK) inhibitors have been approved for patients with ALK-rearrangement lung cancer. The effect is superior to the standard first-line therapy of pemetrexed plus platinum-based chemotherapy. However, ALK inhibitors are associated with rare and sometimes fatal adverse events. Organizing pneumonitis (OP) is a rare and serious adverse event usually caused by ceritinib, and it is easily misdiagnosed as infectious pneumonia, metastasis, or cancer progression.

Patient concerns: A 56-year-old female presented with chest tightness and dyspnea for more than 10 days. She was previously healthy with no significant medical history. Workup including chest computed tomography (CT), pathological examination of a biopsy specimen, and next-generation sequencing was consistent with a diagnosis of IVA ALK-rearrangement lung adenocarcinoma. She was treated with pemetrexed plus platinum-based chemotherapy and crizotinib concurrently, followed by maintenance therapy with crizotinib alone and she had an almost complete response. However, about 26 months after beginning treatment she developed multiple brain metastases. Crizotinib was discontinued and she was begun on ceritinib. After about 3 months the brain metastases had almost complete response. After 5 months of ceritinib, however, multiple patchy lesions appeared in the bilateral upper lungs.

Diagnoses: Treatment with antibiotics had no effect and blood and sputum cultures are negative. A CT-guided biopsy of the upper lung was performed, and pathological hematoxylin-eosin staining and immunohistochemical studies were consistent with OP.

Interventions: Ceritinib was discontinued, she was begun on prednisone 0.5 mg/kg orally every day, and regular follow-up is necessary.

Outcomes: CT of the chest 2 and 4 weeks after beginning prednisone showed the lung lesions to be gradually resolving, and she was continued on prednisone for 2 months and gradually reduced the dose of prednisone every 2 weeks. No related adverse events were occurred in patient.

Lessons: OP must be differentiated from infectious pneumonia, metastasis, or cancer progression. The mechanism of OP is still unknown and needs further research. Biopsy plays a role in making a diagnosis of OP. In our patient, discontinuing ceritinib and treating her with prednisone resulted in a good outcome.

Publication types

  • Case Reports

MeSH terms

  • Adenocarcinoma of Lung* / drug therapy
  • Adenocarcinoma of Lung* / genetics
  • Adenocarcinoma of Lung* / pathology
  • Adenocarcinoma of Lung* / physiopathology
  • Anaplastic Lymphoma Kinase* / antagonists & inhibitors
  • Anaplastic Lymphoma Kinase* / genetics
  • Antineoplastic Agents / therapeutic use
  • Biopsy / methods
  • Brain Neoplasms / drug therapy
  • Brain Neoplasms / secondary
  • Crizotinib / therapeutic use
  • Cryptogenic Organizing Pneumonia* / chemically induced
  • Cryptogenic Organizing Pneumonia* / pathology
  • Cryptogenic Organizing Pneumonia* / therapy
  • Drug Substitution
  • Enzyme Inhibitors / administration & dosage
  • Enzyme Inhibitors / adverse effects
  • Female
  • High-Throughput Nucleotide Sequencing / methods
  • Humans
  • Lung / diagnostic imaging
  • Lung / pathology
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / genetics
  • Lung Neoplasms* / pathology
  • Lung Neoplasms* / physiopathology
  • Middle Aged
  • Pemetrexed / therapeutic use
  • Prednisone / administration & dosage*
  • Pyrimidines* / administration & dosage
  • Pyrimidines* / adverse effects
  • Sulfones* / administration & dosage
  • Sulfones* / adverse effects
  • Tomography, X-Ray Computed / methods
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Enzyme Inhibitors
  • Pyrimidines
  • Sulfones
  • Pemetrexed
  • Crizotinib
  • Anaplastic Lymphoma Kinase
  • ceritinib
  • Prednisone