Evaluation of Lung Toxicity With Lenalidomide Using the Pharmacovigilance Database

Background/Aim: Lenalidomide (LND) is an oral anticancer drug used to treat various malignant hematologic diseases, including multiple myeloma. The most common adverse events with LND are myelosuppression, thrombosis and pneumonia. Myelosuppression is reversible, and thrombosis can be treated with prophylactic administration of antithrombotic drugs. Pneumonia is less common and its incidence profile in clinical studies is unclear. This study aimed to evaluate the incidence and onset timing of LND-related lung toxicity and outcome details using the Japanese Adverse Drug Event Report (JADER) database. Patients and Methods: Adverse events with LND reported between April 2004 and March 2021 were selected. Data on lung adverse drug reactions (ADRs) were analyzed, and safety signals were estimated using reported odds ratios (RORs) and 95% confidence intervals (CIs). We also estimated the timing of onset of lung toxic signs. Results: A total of 10,929 ADRs were attributed to LND. Of these, 908 were lung toxicities. The most frequently reported ADRs with significantly high RORs were pneumonia (559 cases, ROR=3.89, 95% CI=3.57-4.24) and bacterial pneumonia (38 cases, ROR=2.02, 95% CI=1.46-2.78). Median onset of pneumonia and bacterial pneumonia were 84 and 74 days, respectively. Prognoses of patients who received LND and had pneumonia and bacterial pneumonia were poor, with 10-20% non-recovery and deaths. Conclusion: The findings indicate that pneumonia and bacterial pneumonia, among all LND-related lung toxicities, may be associated with immunosuppression, suggesting the importance of monitoring respiratory symptoms within the first 3 months of treatment.