Incidence of severe chemotherapy-associated nausea and vomiting with brentuximab vedotin and AVD in comparison with ABVD using standard anti-emetic prophylaxis

Abstract

Abstract Introduction: Chemotherapy-induced nausea and vomiting (CINV) remains an important side effect of chemotherapy for patients with classical Hodgkin's Lymphoma (cHL). The BV-AVD (brentuximab vedotin- doxorubicin, vinblastine, dacarbazine) regimen for cHL improves overall survival in advanced stage disease in comparison to ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine), however, the comparative incidence of CINV with BV-AVD relative to ABVD is not well described. We hypothesized that patients receiving BV-AVD experience a higher incidence of severe breakthrough nausea and vomiting with standard anti-emetic prophylaxis than patients receiving ABVD. Methods:A retrospective chart review was completed for individuals with cHL treated with either ABVD or BV-AVD at The Ohio State University James Cancer Hospital between January 1, 2011 and January 1, 2024. 87 patients receiving ABVD and 57 patients receiving BV-AVD were graded retrospectively for nausea (assigned a score of 1-4) and vomiting (assigned a score of 1-5) based on the Common Terminology for Adverse Events Version 5. Severe nausea was defined as a grade of 2-4. Differences in baseline characteristics between the treatment groups (BV-AVD vs ABVD) and outcomes related to CINV were compared using Fisher's Exact test and Chi-Square test for categorical variables and Wilcoxon rank sum test for numeric variables. Logistic regression was performed to determine association between baseline characteristics, including treatment regimen, and incidence of severe nausea and vomiting. Results:Baseline characteristics of patients who received BV-AVD and ABVD were compared. All patients received anti-emetic prophylaxis of palonosetron and dexamethasone with the first cycle of treatment. The median age of diagnosis for the ABVD group (30 years) and the BV-AVD group (34 years) were similar (p=0.48). The proportion of each gender for the ABVD group (53% male, 47% female) and for the BV-AVD group (60% male, 40% female) were also similar (p=0.42). The median stage of disease at diagnosis was higher for the BV-AVD group at 4 vs 3 for the ABVD group (p<0.0001). The BV-AVD group also had a higher incidence of baseline nausea (21% vs 9%, p=0.04). Outcome variables for each treatment were compared. The median number of BV-AVD cycles received was 6 (range 1-6), while the median number of cycles of ABVD was 5 (range 2-6, p= 0.01). There was no significant difference in the number of patients in each group who escalated anti-emetic prophylaxis to include a neurokinin-1 receptor antagonist after starting treatment (26 for ABVD vs 28 for BV-AVD, p= 0.10). Notably, patients receiving BV-AVD experienced a significantly higher incidence of severe nausea compared to ABVD patients (44% vs 20%, p<0.01). In addition, patients receiving BV-AVD had significantly more hospitalizations for CINV (14% vs 2%, p=0.01), hospitalizations or ED visits for CINV (18% vs 2%, p<0.01), and a greater proportion of patients with significant weight loss (loss of ≥5% of body weight or ≥10 lbs) due to CINV (40% vs 7%, p<0.0001). The BV-AVD group experienced a numerically higher incidence of vomiting (any grade) than the ABVD group (53% vs 41%), however the difference was not significant (p=0.19). The impact of baseline characteristics on incidence of severe nausea or vomiting was analyzed. While the median stage of disease at diagnosis and incidence of baseline nausea was greater for the BV-AVD group, there was no significant relationship of these variables to the incidence of severe nausea or incidence of vomiting. Age at diagnosis and gender also did not correlate with the incidence of either severe nausea or vomiting. The only variable that had a significant association with the incidence of severe nausea was treatment regimen, with a BV-AVD vs ABVD odds ratio of 3.22 (95% CI 1.53-6.77). Conclusions:We observed a higher incidence of severe nausea in patients with cHL who were treated with BV-AVD as compared to ABVD, when receiving the same standard anti-emetic prophylaxis. Patients treated with BV-AVD also experienced more hospitalizations for CINV, combined hospitalizations or ED visits for CINV, and significant weight loss due to CINV. The results of this study suggest that patients receiving BV-AVD for cHL may benefit from more intensive anti-emetic prophylaxis compared with patients receiving ABVD.