ID #1147 Targeted therapy including Dordaviprone in progressive/recurrent diffuse midline Gliomas- access, toxicity/efficacy and challenges- an LMIC experience
Uday Krishna AS, Krishna Kumar, Aravind Sukumaran, Adhityan Rajendran, Sushama Patil, Pankaj Kumar Panda, Ari Chacko, Srinivas Chilukuri, Rakesh JalaliAbstract
Objective
Efficacy of post radiation salvage therapy of 65 patients with diffuse midline gliomas was evaluated for efficacy/toxicity and access to Dordaviprone
Methods
Between May 2023 and December 2025, 65 patients (median age- 13 y, M: F- 63% Vs. 37%), were assessed for feasibility of biopsy with MRI & MDT for HPR/IHC/NGS. H3K27M mutant DMG was found in 46/65. All received radical RT- Tomotherapy vs. IM- Protons based on the patient preference & dosimetry to a dose of 54Gy in 30 fractions. At the follow up of 3 months of MRI evalaution of RANO. At progression/ recurrence, 70% of these patients opted further therapy, choice of therapy made in MDT- Bevacizumab with or without Dordaviprone until further progression, second course of radiation or palliative care. 14/35 patients received Dordaviprone, alone or in combination. For ease of analysis, the cohort was divided based on additonal mutations (BRAF/H3me3 loss).
Results
In the group of H3K27M mutant DMG (34/46) 20 patients, the performance status of the patients was reasonable to provide any systemic therapy prior to the second course of radiation. 6/34 did not receive Dordaviprone while 14/34 opted to procure Dordaviprone from various sources- 2 procured it from USA on a compassionate basis being citizens of USA. Among the other 10/12, 2 were prior to the FDA approval and 10 were after the FDA approval of Dordaviprone. At a median follow up of 6 months from the first progression (3 to 12 months), 50% of the patients who received Dordaviprone are alive with disease. Among these, 4/7 had progressed with a posterior fossa/upper spinal disease, one child had spinal DMG (had 2 courses of radiation and 6 cycles of Bevacizumab prior) with twice-weekly Dordaviprone and 2 are young adults who had TMZ at first progression and switched to Dordaviprone upon radiological PD. Median dose of the Dordaviprone was 375mg twice a week. None of them developed toxicity related to the drug. At a median follow up of 6 months in the entire cohort, PFS-1-D, defined as PFS after first progression with Dordaviprone (with additional therapies) was significantly higher compared to those who received any monotherapy without Dordaviprone (6m vs 2m).
Conclusion
Improved access with FDA approval, increasing awareness among families, favourable toxicity profile, early improved efficacy in addition to other therapies, Dordaviprone is promising as a salvage regimen for children with DMG from LMIC