Outcome of grade 3 and 4 cytopenia in newly diagnosed glioblastoma multiforme (GBM) patients treated with temozolomide (TMZ).

Abstract

2018 Background: Current standard treatment for GBM consists in radiotherapy (RT) plus concomitant and adjuvant (adj) TMZ. Myelosupression is the dose limiting toxicity of TMZ with grade 3 and 4 cytopenia occurring in ~16%. We describe the difference in outcome of newly diagnosed GBM patients treated with TMZ who developed grade 3 and 4 cytopenia. Methods: A 10-year retrospective analysis of newly diagnosed adult GBM patients (pts) treated with first-line TMZ. All pts received concurrent TMZ and RT with or without investigational drug. If the pt did not progress on magnetic resonance imaging (MRI) adj TMZ was given. Cytopenia events during TMZ therapy were graded using the National Cancer Institute Common Toxicity Criteria (v3). Survival distribution was estimated by the Kaplan-Meier method. Results: Of 191 pts, 23% developed grade 3 and 4 cytopenia. 74% pts were ≤ 65 years, 75% had 80-100% karnofsky performance status and 78% had surgical resection at diagnosis. 93% pts received 6 wks of concurrent RT 60 Gy and TMZ 75 mg/m2/d. The median dose of adj TMZ was 150-200 mg/m2/d1-d5 every 28d cycle. The median cycles was 4 (range, 0-24). The median progression free survival (PFS) was 6.7 months (mo). The 6 mo and 12 mo PFS for pts who had grade 3 and 4 cytopenia was 73% (95% confidence interval [CI], 57%-83%) and 33% (95% CI, 20%-47%); while in pts with no grade 3 and 4 cytopenia was 51% (95% CI, 43%-59%) and 24% (95% CI, 17.9%-31.8%). The unadjusted hazard ratio (HR) for death or disease progression of pts with grade 3 and 4 cytopenia, as compared to those without grade 3 and 4 cytopenia, was 0.58 [95% CI, 0.40 to 0.82; p< 0.003]. The HR for death or disease progression was 0.68 (95% CI, 0.47-0.98; p<0.045) among those with a methylated MGMT promoter. The total dose of TMZ was not different between both groups (p=0.284 by Wilcoxon rank sum test). Conclusions: Our study supports that newly diagnosed GBM pts who develop grade 3 and 4 cytopenia during TMZ therapy have improved PFS. Further clinical trials are required to validate grade 3 and 4 cytopenia as a potential biomarker for TMZ efficacy in an attempt to optimize and personalize GBM therapy.