Association Between Proton Pump Inhibitor Use and Febrile Neutropenia During R-CHOP Therapy in Patients With Non-Hodgkin Lymphoma

Background/Aim: Febrile neutropenia (FN) is an oncologic emergency, making the identification of its risk factors critical. Proton pump inhibitor (PPI) use has recently been reported as a risk factor for FN. However, no studies have evaluated the impact of PPI use on FN by individual chemotherapy regimen in malignant lymphoma, and its impact during rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) therapy remains unclear. Therefore, this study examined the impact of PPI use on FN during R-CHOP therapy. Patients and Methods: This study was a single-center retrospective study including patients who received R-CHOP therapy for non-Hodgkin lymphoma (NHL) at Osaka Metropolitan University Hospital from January 2012 to December 2022. The primary analysis used conditional logistic regression after 1:1 propensity score matching (PSM). For the sensitivity analysis, logistic regression was performed using inverse probability of treatment weighting (IPTW). Results: Among 163 patients, 25 (15.3%) developed FN. FN occurred in 18 of 85 patients (21.2%) in the PPI group and 7 of 78 patients (9.0%) in the non-PPI group. After PSM, 58 matched pairs were included in the analysis. In the propensity score-matched analysis, PPI use was associated with significantly higher odds of FN [odds ratio (OR)=6.50; 95% confidence interval (CI)=1.47-28.8; p=0.014]. The IPTW analysis showed a trend toward higher odds of FN with PPI use, although the difference was not statistically significant (OR=2.40; 95%CI=0.89-6.48; p=0.084). Conclusion: PPI use may be associated with an increased risk of FN in patients with NHL receiving R-CHOP therapy.