NIMG-81. EFFECT OF RE-TREATMENT WITH TEMOZOLOMIDE IN GRADE 2/3 IDH MUTANT GLIOMAS AT FIRST PROGRESSION

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Abstract BACKGROUND Patients with WHO grade 2 and 3 IDHmt gliomas commonly receive temozolomide, with or without radiation therapy, as initial therapy. At progression, temozolomide is sometimes reinstated despite a paucity of data on effectiveness. METHODS We reviewed imaging outcomes of patients with grade 2/3 IDHmt gliomas re-treated with temozolomide at first progression between 2007 and 2019. RESULTS 15 subjects included six grade 2 and five grade 3 oligodendrogliomas, one grade 2 and three grade 3 astrocytomas. Median time between completion of first temozolomide course and initiation of re-treatment was 47 months (range, 8-126 months). Best treatment response after first progression by RANO criteria was stable disease in 10 and progressive disease in 5 patients. Median progression free survival with temozolomide re-treatment was 27.4 months (95% CI: [13.8, 41.2 months] and median overall survival 47.8 months (95% CI: [31.5, 125.6 months]). In 14 patients who had pre- and post- first tumor progression rate measurements, the mean rate of tumor growth by bidimensional product was 0.29 cm2/month (95% CI: [0.17, 0.42 cm2/month], p< 0.001) prior to first tumor progression versus 0.47 cm2/month (95 CI: [0.08, 0.85 cm2/month], p=0.021) during re-treatment with monotherapy temozolomide (prior vs after, p=0.371). The volumetric mean rate of tumor growth was 1.12 cc/month (95% CI: [0.31, 1.93 cc/month], p=0.010) prior to first tumor progression versus 1.29 cc/month (95% CI: [0.15, 2.43 cc/month], p=0.030) during temozolomide re-treatment (prior vs. after, p=0.802). CONCLUSION Among 15 patients with progressive IDHmt glioma re-treated with temozolomide, there was no radiographic response by RANO criteria nor a decrease in tumor growth rate during the re-treatment period compared to immediate pre-re-treatment period. These findings suggest previously treated, progressive IDHmt gliomas are generally resistant to temozolomide, underscoring the need for novel therapies.