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331 Tumor markers associated with increased survival in a phase II trial of dendritic cell/tumor-initiating-cell vaccine AV-GBM-1 in patients with newly diagnosed glioblastoma
  1. Daniela Bota1,
  2. David Piccioni2,
  3. Christopher Duma3,
  4. Renato LaRocca4,
  5. Santosh Kesari5,
  6. Jose Carrillo5,
  7. Frank Hsu1,
  8. Xiao-Tang Kong1,
  9. Mehrdad Abedi6,
  10. Robert Aiken7,
  11. Thomas Taylor1,
  12. Candace Hsieh8,
  13. Gabriel Nistor8 and
  14. Robert Dillman8
  1. 1University of California Irvine, Orange, CA, USA
  2. 2University of California San Diego, San Diego, CA, USA
  3. 3Hoag NeuroSciences Institute, Newport Beach, CA, USA
  4. 4Norton Cancer Institute, Louisville, KY, USA
  5. 5John Wayne Cancer Institute, Santa Monica, CA, USA
  6. 6University of California Davis, Sacramento, CA, USA
  7. 7Rutgers Cancer Center, New Brunswick, NJ, USA
  8. 8AIVITA Biomedical Inc., Irvine, CA, USA


Background Standard aggressive therapy of glioblastoma (GBM), which includes maximum safe resection, concurrent radiation therapy and temozolomide chemotherapy (RT/TMZ) followed by maintenance TMZ, is associated with a 25% 2-year overall survival (OS). Adding treatment with AV-GBM-1, a vaccine consisting of autologous dendritic cells (DC) pulsed with autologous tumor antigens (ATA) may improve OS by inducing and/or enhancing the host anti-GBM immune response. Methylation of the O-6-methylguanine-DNA methyltransferase (MGMT) gene promoter, and mutation of the gene for isocitrate dehydrogenase (IDH) are favorable prognostic markers in newly diagnosed GBM. An objective of a multi-center phase II clinical trial was to determine whether these markers were still prognostic for OS in patients treated with adjunctive AV-GBM-1.

Methods Key eligibility criteria for intent-to-treat (ITT) enrollment were: (1) confirmation of primary GBM, (2) successful GBM cell culture, (3) collection of sufficient numbers of monocytes (MC) by leukapheresis, (4) Karnofsky Performance Status 70 or greater after recovery from surgery, and (5) plan to treat with concurrent RT/TMZ. AV-GBM-1 was manufactured while patients were being treated with RT/TMZ. Interleukin-4 and granulocyte-macrophage colony stimulating factor (GM-CSF) were used to differentiate DC from MC. Each vaccine consisted of autologous DC incubated with ATA from the lysate of irradiated cultured GBM cells grown in serum-free media with factors that favor survival and proliferation of stem cells and early progenitor cells (tumor-initiating cells). After recovery from RT/TMZ, intent was to vaccinate for up to six months with cryopreserved AV-GBM-1 admixed with 500 mg GM-CSF. All patients had testing for MGMT-methylation and IDH-mutation. OS was calculated from date of ITT enrollment.

Results 60 patients were enrolled during August 2018 to January 2020. MGMT promoter methylation was detected in 21 (35%), mutated IDH in 7 (12%), and one or both in 25 (42%). At a minimum follow-up of 15 months, median OS had not been reached for patients with a methylated MGMT promotor, IDH mutation, or one or both, compared to 14.6 months for 38 with unmethylated MGMT promotor (p=0.026), 14.7 months for 53 with IDH wild-type (p=0.044), and 14.6 months for 35 who had neither (p=0.017). 18-month OS rates were 59% vs 35% for MGMT promotor methylation, 71% vs 40% for IDH mutation and 58% vs 32% for either.

Conclusions Both MGMT promotor methylation and IDH mutation were associated with a substantial and similar survival benefit in primary GBM patients treated with AV-GBM-1 in addition to standard aggressive therapy.

Clinicaltrials gov NCT03400917

Ethics Approval This study was approved by the Western IRB, approval number 20182582; all participants gave written informed consent before taking part

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