Successful Crizotinib Rechallenge After Crizotinib-induced Interstitial Lung Disease

Abstract

We report the case of a 70-year-old Japanese male diagnosed with advanced lung adenocarcinoma harboring the echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase fusion gene. As soon as crizotinib was administered, tumor shrank immediately. On Day 25, he developed interstitial lung disease. Bronchoalveolar lavage fluid analysis demonstrated elevated lymphocytes fractionation. A drug lymphocyte stimulating test for crizotinib with the bronchoalveolar lavage lymphocytes was negative. Crizotinib administration was discontinued, but a life-threatening flare of tumor growth occurred. Since there was no alternative treatment for the lung cancer, we restarted crizotinib in combination with prednisolone. The patient experienced neither disease progression nor recurrence of interstitial lung disease at 6 months. In cases in which no alternate treatment is known, crizotinib retreatment combined with steroid therapy after crizotinib-induced interstitial lung disease could be considered after a careful consideration of the potential risks and benefits.

Crizotinib Associated with Ground-Glass Opacity Predominant Pattern Interstitial Lung Disease: A Retrospective Observational Cohort Study with a Systematic Literature Review

“…After a systematic review of the literature, we identified 43 other cases of crizotinib-associated ILD, among which 34 were notified in the PROFILE studies and nine case reports described in more detail [10][11][12][13][14][15][16][17][18] (Table 3).…”

“…Other reported cases had few symptoms like ours (Table 3). 14,16,17 Crizotinib was restarted with corticosteroids, 12,16,17 except in one case. 14 This latter being the only which presented a relapse.…”

Interstitial Lung Disease Onset and Its Risk Factors in Japanese Patients With ALK-Positive NSCLC After Treatment With Crizotinib

“…In contrast, some case reports have indicated successful crizotinib retreatment after crizotinib-induced ILD in patients with the non-DAD pattern, which was characterized by localized or faint ground-glass opacities. 17,30,31 Nevertheless, crizotinib retreatment should be performed under careful consideration of potential risks and benefits even in patients with ILD with the non-DAD pattern, and a careful monitoring is essential. Additionally, the ILD independent review committee reported 8 patients with pulmonary edema-like shadows among 117 patients with ILD, and these 8 patients had no other disease except for ILD, which can cause pulmonary edema-like shadows.…”

Successful alectinib treatment for a mechanically ventilated patient with <i>ALK</i>-positive non-small cell lung cancer

“…On the other hand, no defi nitive diagnosis was established for severe respiratory failure that made further examination difficult and required a prompt response. Crizotinib-induced pneumonitis was considered to be one of possible etiologies of respiratory insufficiency based on the previous reports, some of which showed successful retreatment with an ALK inhibitor after the development of pneumonitis [10][11][12][13] . Particularly, Chino et al reported an ALK-positive patient who had undergone crizotinib-induced pneumonitis was successfully treated with alectinib thereafter 13) .…”