P12.45.b Association Between Temozolomide-Related Hematological Toxicity and Hrqol Scores in Glioblastoma: A Pooled Analysis of Three Randomized Trials

BACKGROUND Hematologic toxicity is the major adverse event of temozolomide chemoradiotherapy for newly diagnosed glioblastoma. Although severe hematologic toxicity occurs in approximately 10% of patients, its impact on health-related quality of life (HRQoL) is unknown. Here, we evaluated the association between temozolomide-related hematologic toxicity and HRQoL in patients with newly diagnosed glioblastoma. MATERIAL AND METHODS We included patients with newly diagnosed glioblastoma undergoing temozolomide chemoradiotherapy with available HRQoL assessments from three clinical trials: EORTC 1709 (MIRAGE), EORTC 26071 (CENTRIC), and EORTC 26981. HRQoL was assessed using the EORTC QLQ-C30 and BN20 questionnaires, and primary HRQoL outcomes were physical, social, and role functioning, pain, fatigue, nausea and vomiting, as well as global health status. To evaluate the association of CTCAE grade 3 or higher hematologic toxicity, including (thrombocytopenia, lymphopenia, anemia, neutropenia) with HRQoL outcomes, we fitted a linear mixed model with hematologic toxicity, time point of HRQoL assessment, an interaction term, and other baseline covariables as fixed effects, and a patient-specific random effect for each outcome. Clinical relevance was interpreted using the newly established minimally important difference (MID) estimates for patients with glioma. RESULTS Among 1288 patients included in the analysis, 105 patients (8%) experienced grade 3-4 hematologic toxicity during the concomitant phase and 82 patients (6%) experienced grade 3-4 hematologic toxicity during the maintenance phase. Severe hematologic toxicity was more frequent in women, patients with tumors with O6-methylguanine DNA methyltransferase (MGMT) promoter methylation, older patients, those with MMSE ≥27, and those with WHO performance status greater than zero. HRQoL analysis showed mean decreases in global quality of life scores at week 6 of 4.78 points for patients without hematologic toxicity and of 8.52 points for those with hematologic toxicity (difference 3.74; 95% CI -2.51 to 9.99; p=0.24). Similar trends were observed at week 18. Both functional and symptom scales showed numerically greater decreases in scores for patients with hematologic toxicity compared with those without at weeks 6 and 18. However, no statistically significant differences were observed. CONCLUSION While severe hematologic toxicity was associated with greater declines in HRQoL and functional domains during the concomitant and maintenance phases, these differences were not statistically significant. Further studies are needed to explore the clinical relevance of these findings.