No abstract

Medications that target programmed cell death protein-1 (PD-1) have proven effective. However, blockade of PD-1/Programmed death-ligand 1(PD-L1) causes immune-related adverse events (irAEs). Characteristics of this irAE include many symptom, low in frequency, and difficulty in prevention. The key to a successful ICI-related treatment lies in the management of irAEs resulting from immune checkpoint inhibitor (ICI) treatment. Although it is difficult to predict irAE, we tried to extract features of irAE expression from analysis of real-world database. This study used data extracted from the Japan Adverse Drug Event Report (JADER) database to assess risk factors associated with serious side effects of irAE, type 1 diabetes (T1DM). The analysis targets were nivolumab, atezolizumab, durvalumab, and pembrolizumab, and the study period was from July 2014 to June 2019. Analysis of Japanese population data confirmed that being women and having melanoma were risk factors for developing ICI-related T1DM. Analysis using this database in combination with information on ICI-related T1DM provides information and guidelines that will help in the safer treatment of ICI in the future.

Background: The degrees of adverse effects with carboplatin (CBDCA) are influenced by interindividual differences in the area under the curve (AUC), whereas renal function is not considered in the CBDCA dose design for dexamethasone, etoposide, ifosfamide, and CBDCA (DeVIC) therapy. We conducted this study to evaluate the association between the AUC and incidence of severe thrombocytopenia in patients treated with DeVIC with or without rituximab (DeVIC ± R). Methods: We retrospectively analyzed clinical data for 36 patients with non-Hodgkin’s lymphoma who received DeVIC ± R between May 2013 and January 2021 at the National Hospital Organization Hokkaido Cancer Center. The AUC of CBDCA (AUC actual ) was calculated backward using a variant of the Calvert formula. Results: The median AUC actual was 4.6 (interquartile range: 4.3–5.3) min mg/mL and AUC actual was negatively correlated with the nadir platelet count (r = -0.45; P < 0.01). Multivariate analysis showed that AUC actual ≥ 4.3 versus < 4.3 was an independent factor predictive of severe thrombocytopenia (odds ratio: 19.3, and 95% confidence interval: 1.45–258; P = 0.02). Conclusion: This study suggests that the CBDCA dosing design considering renal function can reduce the risk of severe thrombocytopenia in DeVIC ± R therapy.