Hemolytic anemia following alectinib reported to the U.S. Food and Drug Administration Adverse Event Reporting System

Abstract

The U.S. Food and Drug Administration (FDA) encourages submission of suspected adverse events for drug and biologic products to the FDA Adverse Event Reporting System (FAERS) through MedWatch (www.fda.gov/medwatch). Due to reference limitations, the authors were unable to cite all literature reports submitted to FAERS describing red cell morphology abnormalities and/or hemolytic anemia following exposure to alectinib.

Alectinib-Induced Severe Hemolytic Anemia in a Patient with ALK-Positive Non-Small Cell Lung Cancer: A Case Report

“…Most of the cases reported developed mild and acute (within 90 days) hemolysis and anemia is generally reversible with discontinuation of alectinib. 11 In our case report, although grade 4 anemia first appeared after about 3 years, T-Bil and LDH were already elevated above baseline one month after the start of alectinib, followed by a decrease in hemoglobin level. Therefore, the anemia that appeared about 2 months after alectinib administration was considered the first hemolytic event in this patient.…”

Alectinib-induced Hemolytic Anemia with Positive Direct Antiglobulin Test in a Patient with Lung Adenocarcinoma: A Possible Drug-drug Interaction Effect

“…DATs were found to be negative in all of these reports, and peripheral blood smears showed abnormal erythrocyte morphology. The U.S. Food and Drug Administration's adverse event reporting system reported 31 cases of alectinib-induced hemolytic anemia between 2015 and 2021, 11 of which were DAT-negative ( 8 ). In a small prospective study, 13 of 19 alectinib-treated patients had anemia, and of the 11 patients (with and without anemia) who were selected for further testing, all had negative DAT results, and all showed morphological changes in erythrocytes after peripheral blood smears ( 9 ).…”

“…DATs were found to be negative in all of these reports, and peripheral blood smears showed abnormal erythrocyte morphology. The U.S. Food and Drug Administration's adverse event reporting system reported 31 cases of alectinib-induced hemolytic anemia between 2015 and 2021, 11 of which were DAT-negative (8).…”

Expert consensus of management of adverse drug reactions with anaplastic lymphoma kinase tyrosine kinase inhibitors

“…A low Hb concentration and/or low hematocrit are the parameters most widely used to diagnose anemia in clinical trials for ALK-TKIs and patients who received ensartinib, crizotinib, and alectinib are at high risk of anemia ( Supplementary Table S11 , available at https://doi.org/10.1016/j.esmoop.2023.101560 ). Notably, hemolytic anemia is rare but has been reported with alectinib, 24 , 44 including cases associated with a negative direct antiglobulin test result.…”