Abstract 4754: Type-1 dendritic cell vaccines in combination with poly-ICLC-association between positive tetramer response and 6-month progression-free survival in patients with recurrent malignant glioma

2098 Background: Bevacizumab (Bev) and irinotecan combination therapy is effective against recurrent malignant glioma. However, post-Bev treatment and its clinical outcomes are not well investigated. Methods: We identified 103 consecutive recurrent malignant glioma patients who received Bev plus irinotecan at our institutions.Clinical records and magnetic resonance images were reviewed. Response and progression were assessed by RANO criteria. Results: Bev and irinotecan treatment produced response rate of 37.9% (95% CI, 29.1-47.5%). At a median follow-up time of 41 weeks, the median progression-free survival (PFS) was 17.1 weeks (95% CI, 14.3-20.0), and 6-month PFS (6M-PFS) was 27.8% (95% CI, 18.4-37.2). The median overall survival (OS) was 33.4 weeks (95% CI, 27.8-39.1). Response predicted for superior PFS (25.0 weeks vs. 11.0 weeks, p < .001) and OS (45.9 weeks vs. 26.7 weeks, p < .001). A total of 93 patients discontinued Bev treatment and the reasons for discontinuation were: disease progression in 59 (63.4%), toxicities in 4 (4.3%), physician’s decision in 5 (5.4%), patient’s refusal to further treatment in 25 (26.9%). The median OS was 26.7 weeks in 59 patients who discontinued Bev due to disease progression, and 45.7 weeks in 34 patients who discontinued Bev for reasons other than disease progression (p < .001). Among 85 patients who progressed after Bev, 42 (49.4%) received further therapy: chemotherapy in 32 (37.6%), radiotherapy in 9 (10.6%), and surgery in 1 (1.2%). Further chemotherapy regimens included temozolomide (31.2%), ACNU/CDDP (25.0%), Bev reintroduction (18.8%), erlotinib (12.5%), PCV (9.4%), and intrathecal methotrexate (3.1%). The median survival time after Bev failure was 15.6 weeks (95% CI, 13.3-17.8). Patients who received further therapy showed longer median OS (18.6 weeks vs. 12.9 weeks, p < .001). In patients who received chemotherapy, the median PFS and OS was 6.6 weeks and 20.6 weeks, respectively. Conclusions: Prognosis after Bev failure was poor. Proper selection of patients who may benefit from further treatment is warranted.

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Abstract 2306: Treatment with hTERT/survivin mRNA-loaded dendritic cells combined with autologousex vivoexpanded T cells improves progression free survival in stage IV melanoma patients when compared to dendritic cell vaccines alone

10.1158/1538-7445.am2016-2306 ◽

2016 ◽

Author(s):

Iris Bigalke ◽

Elin Aamdal ◽

Siri Torhaug ◽

Marianne Lundby ◽

Else M. Inderberg ◽

...

Keyword(s):

T Cells ◽

Dendritic Cells ◽

Dendritic Cell ◽

Stage Iv ◽

Progression Free Survival ◽

Survivin Mrna ◽

Free Survival ◽

Dendritic Cell Vaccines ◽

Melanoma Patients ◽

Stage Iv Melanoma

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Phase II Study of Aflibercept in Recurrent Malignant Glioma: A North American Brain Tumor Consortium Study

Journal of Clinical Oncology ◽

10.1200/jco.2010.34.1636 ◽

2011 ◽

Vol 29 (19) ◽

pp. 2689-2695 ◽

Cited By ~ 138

Author(s):

John F. de Groot ◽

Kathleen R. Lamborn ◽

Susan M. Chang ◽

Mark R. Gilbert ◽

Timothy F. Cloughesy ◽

...

Keyword(s):

Growth Factor ◽

Malignant Glioma ◽

Phase Ii ◽

Phase Ii Study ◽

Single Agent ◽

Progression Free Survival ◽

Recurrent Glioblastoma ◽

Anaplastic Glioma ◽

Recurrent Malignant Glioma ◽

Free Survival

Purpose Antivascular endothelial growth factor (anti-VEGF) therapy is a promising treatment approach for patients with recurrent glioblastoma. This single-arm phase II study evaluated the efficacy of aflibercept (VEGF Trap), a recombinantly produced fusion protein that scavenges both VEGF and placental growth factor in patients with recurrent malignant glioma. Patients and Methods Forty-two patients with glioblastoma and 16 patients with anaplastic glioma who had received concurrent radiation and temozolomide and adjuvant temozolomide were enrolled at first relapse. Aflibercept 4 mg/kg was administered intravenously on day 1 of every 2-week cycle. Results The 6-month progression-free survival rate was 7.7% for the glioblastoma cohort and 25% for patients with anaplastic glioma. Overall radiographic response rate was 24% (18% for glioblastoma and 44% for anaplastic glioma). The median progression-free survival was 24 weeks for patients with anaplastic glioma (95% CI, 5 to 31 weeks) and 12 weeks for patients with glioblastoma (95% CI, 8 to 16 weeks). A total of 14 patients (25%) were removed from the study for toxicity, on average less than 2 months from treatment initiation. The main treatment-related National Cancer Institute Common Terminology Criteria grades 3 and 4 adverse events (38 total) included fatigue, hypertension, and lymphopenia. Two grade 4 CNS ischemias and one grade 4 systemic hemorrhage were reported. Aflibercept rapidly decreases permeability on dynamic contrast enhanced magnetic resonance imaging, and molecular analysis of baseline tumor tissue identified tumor-associated markers of response and resistance. Conclusion Aflibercept monotherapy has moderate toxicity and minimal evidence of single-agent activity in unselected patients with recurrent malignant glioma.

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EPCT-13. CMV PP65 RNA-PULSED DENDRITIC CELL VACCINES FOR PEDIATRIC GLIOBLASTOMA AND MEDULLOBLASTOMA: PHASE I TRIAL RESULTS

Neuro-Oncology ◽

10.1093/neuonc/noaa222.136 ◽

2020 ◽

Vol 22 (Supplement_3) ◽

pp. iii306-iii306

Author(s):

Daniel Landi ◽

Gary Archer ◽

Timothy Driscoll ◽

Eric Lipp ◽

Bridget Archambault ◽

...

Keyword(s):

Dendritic Cell ◽

Phase I ◽

Malignant Glioma ◽

Phase I Trial ◽

Active Immunization ◽

Monocyte Differentiation ◽

Dendritic Cell Vaccines ◽

Dc Vaccines ◽

Subsequent Phase ◽

Children And Young Adults

Abstract BACKGROUND Recurrent medulloblastoma and malignant glioma are lethal tumors that are virtually incurable. The cytomegalovirus (CMV) antigen pp65 is ubiquitously expressed on medulloblastoma and malignant glioma but not on healthy brain. We evaluated autologous CMV pp65 RNA-pulsed dendritic cell (DC) vaccines in children and young adults in a phase I trial. METHODS Circulating monocytes were harvested using leukapheresis, differentiated into DCs, matured, and pulsed with pp65 RNA using electroporation. DCs were packaged into vaccines (2x107DC/vaccine) and administered intradermally following tetanus-diphtheria toxoid site preconditioning every 2 weeks x3, then monthly. The primary objectives of the study were to establish the feasibility of generating at least 3 vaccines and safety. An exploratory objective was to evaluate the ability of vaccination to create and enhance patient pp65-specific T cell responses. RESULTS Eleven patients were enrolled with medulloblastoma (n=3) or glioblastoma (n=8). Ages ranged from 9–30 years old (mean 15.5y). Ten of 11 patients (91%) generated at least 3 vaccines (mean 6.2). Eight patients received at least 3 vaccines. To date, 4 patients have received all generated vaccines without progression, 4 patients have progressed, and 2 patients are still receiving vaccines. There have not been any severe adverse events probably or definitely related to vaccines. More mature data will be presented at ISPNO. CONCLUSIONS Leukapheresis and monocyte differentiation is a feasible strategy for generating adequate DCs for active immunization in children with malignant brain tumors. CMV pp65 RNA-pulsed DCs are well-tolerated and immunogenic. Efficacy endpoints will be evaluated in a subsequent phase II trial.

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Transient local response and persistent tumor control in a child with recurrent malignant glioma: treatment with combination therapy including dendritic cell therapy

Journal of Neurosurgery Pediatrics ◽

10.3171/ped.2004.100.5.0492 ◽

2004 ◽

Vol 100 (5) ◽

pp. 492-497 ◽

Cited By ~ 17

Author(s):

Steven De Vleeschouwer ◽

Frank Van Calenbergh ◽

Philippe Demaerel ◽

Patrick Flamen ◽

Stefan Rutkowski ◽

...

Keyword(s):

Dendritic Cell ◽

Combination Therapy ◽

Cell Therapy ◽

Malignant Glioma ◽

Tumor Control ◽

Recurrent Malignant Glioma ◽

Local Response ◽

Dendritic Cell Therapy

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Bevacizumab plus etoposide among recurrent malignant glioma patients: Phase II study final results

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.2046 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. 2046-2046

Author(s):

D. Reardon ◽

A. Desjardins ◽

J. J. Vredenburgh ◽

S. Gururangan ◽

K. B. Peters ◽

...

Keyword(s):

Malignant Glioma ◽

Intracranial Hemorrhage ◽

Progression Free Survival ◽

Therapeutic Benefit ◽

Primary Outcome Measure ◽

Recurrent Malignant Glioma ◽

Neutralizing Monoclonal Antibody ◽

Grade 3 ◽

Endothelial Growth Factor

2046 Background: Significant therapeutic benefit has been observed among recurrent malignant glioma (MG) patients treated with bevacizumab (BV), a neutralizing monoclonal antibody to vascular endothelial growth factor (VEGF) with or without chemotherapy. In this study, we evaluate the efficacy of BV plus etoposide (E), a topoisomerase inhibitor, among recurrent MG patients. Methods: Recurrent patients with no more than three prior episodes of recurrence are eligible, while those with prior BV treatment or prior intracranial hemorrhage are excluded. The primary outcome measure is 6 month progression-free survival (6-PFS). BV is dosed at 10 mg/kg intravenously every other week. Etoposide is orally administered daily (50 mg/m2) for days 1–21 of each 28-day cycle. Results: Fifty-nine patients (GBM, n = 27; grade 3 MG, n = 32) with a median of 2 prior progressions have enrolled. With a median follow-up of 45 weeks, median overall survival (OS) for GBM and grade 3 MG patients were 46 and 47 weeks, while the 6-PFS is 44% and 40.6%, respectively. The most common toxicities were neutropenia (41%), fatigue (22%), and infection (20%) and were grade 2 in most cases. One patient developed grade 1 intracranial hemorrhage and 1 patient had a grade 4 GI perforation. Conclusions: Combination of bevacizumab and etoposide is well tolerated in recurrent MG patients and is associated with encouraging anti-tumor benefit. Accrual is complete and an update of further treatment and follow-up will be presented. No significant financial relationships to disclose.

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