pf-06463922 and Sarcoidosis

Anaplastic lymphoma kinase (ALK) rearranged lung cancers represent 4% to 6% of all pulmonary adenocarcinomas, and echinoderm microtubule associated protein like 4 (EML4)-ALK fusions are the most common subgroup. Herein, we report a case of two successive drug reactions due to ALK inhibitors. A 69-year-old female with stage IVB EML4-ALK fused lung adenocarcinoma developed a generalized morbilliform eruption 10 days after starting alectinib. Skin biopsy findings were consistent with a drug reaction. Her findings resolved after alectinib was discontinued. Another ALK inhibitor, lorlatinib was started and she developed multiple asymptomatic cutaneous and oral nodules 4 months later. Biopsies from these nodules showed sarcoidal granulomas without evidence of metastases or infection. ALK inhibitors are associated with numerous adverse events, including various cutaneous eruptions. However, a sarcoidal drug reaction involving the skin has not been reported. Identification of drug reactions to targeted therapy can avoid long-term sequelae and misinterpretation of the clinical findings as disease progression or infection.

Topics: Adenocarcinoma of Lung; Aged; Aminopyridines; Anaplastic Lymphoma Kinase; Biopsy; Carbazoles; Cell Cycle Proteins; Drug-Related Side Effects and Adverse Reactions; Female; Granuloma; Humans; Lactams; Microtubule-Associated Proteins; Neoplasm Staging; Piperidines; Protein Kinase Inhibitors; Pyrazoles; Sarcoidosis; Serine Endopeptidases; Skin; Withholding Treatment

The administration of target inhibitors is paramount to grant the longest survival in patients with ALK-positive non-small cell lung cancer (NSCLC). The eventual resistance to tyrosine kinase inhibitors (TKI) is monitored clinically and radiologically for prompt molecule shift to further generation TKI, if available. However, the early radiological detection of progression pattern (e.g. nodule onset) should be regarded with caution because overlaps exist with non-tumor cell proliferation and/or accumulation. Here we report the case of a stage IV ALK-rearranged NSCLC patient exposed to serial crizotinib, brigatinib, ceritinib, and lorlatinib (this latter brought to complete brain and leptomeningeal disease response), in a period of more than five years. During lorlatinib, the appearance of solid pulmonary nodules was obviously interpreted as disease progression. However, surgical biopsies of the pulmonary nodules revealed features of sarcoid-like granulomatous lymphadenitis, namely without tumor cell. This invasive approach, besides documenting for the first time a sarcoid-like reaction to ALK inhibitors, allowed to revert the radiological diagnosis and maintain lorlatinib, for the best patient outcome. The pragmatic relevance of these findings suggests a careful attitude towards the interpretation of radiologic patterns of disease progression in patients under TKI.

Topics: Adult; Aminopyridines; Anaplastic Lymphoma Kinase; Carcinoma, Non-Small-Cell Lung; Diagnosis, Differential; Disease Progression; Female; Gene Rearrangement; Humans; Lactams; Lactams, Macrocyclic; Lung Neoplasms; Prognosis; Pyrazoles; Sarcoidosis