First results on survival from a large Phase 3 clinical trial of an autologous dendritic cell vaccine in newly diagnosed glioblastoma

Linda M. Liau, Keyoumars Ashkan, David D. Tran, Jian L. Campian, John E. Trusheim, Charles S. Cobbs, Jason A. Heth, Michael Salacz, Sarah Taylor, Stacy D. D'Andre, Fabio M. Iwamoto, Edward J. Dropcho, Yaron A. Moshel, Kevin A. Walter, Clement P. Pillainayagam, Robert Aiken, Rekha Chaudhary, Samuel A. Goldlust, Daniela A. Bota, Paul Duic & 49 others Jai Grewal, Heinrich Elinzano, Steven A. Toms, Kevin O. Lillehei, Tom Mikkelsen, Tobias Walpert, Steven R. Abram, Andrew Brenner, Steven Brem, Matthew G. Ewend, Simon Khagi, Jana Portnow, Lyndon J. Kim, William G. Loudon, Reid C. Thompson, David E. Avigan, Karen L. Fink, Francois J. Geoffroy, Scott Lindhorst, Jose Lutzky, Andrew E. Sloan, Gabriele Schackert, Dietmar Krex, Hans Jorg Meisel, Julian Wu, Raphael P. Davis, Christopher Duma, Arnold B. Etame, David Mathieu, Santosh Kesari, David Piccioni, Manfred Westphal, David S. Baskin, Pamela Z. New, Michel Lacroix, Sven Axel May, Timothy J. Pluard, Victor Tse, Richard M. Green, John L. Villano, Michael Pearlman, Kevin Petrecca, Michael Schulder, Lynne P. Taylor, Anthony E. Maida, Robert M. Prins, Timothy F. Cloughesy, Paul Mulholland, Marnix L. Bosch

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Background: Standard therapy for glioblastoma includes surgery, radiotherapy, and temozolomide. This Phase 3 trial evaluates the addition of an autologous tumor lysate-pulsed dendritic cell vaccine (DCVax®-L) to standard therapy for newly diagnosed glioblastoma. Methods: After surgery and chemoradiotherapy, patients were randomized (2:1) to receive temozolomide plus DCVax-L (n = 232) or temozolomide and placebo (n = 99). Following recurrence, all patients were allowed to receive DCVax-L, without unblinding. The primary endpoint was progression free survival (PFS); the secondary endpoint was overall survival (OS). Results: For the intent-to-treat (ITT) population (n = 331), median OS (mOS) was 23.1 months from surgery. Because of the cross-over trial design, nearly 90% of the ITT population received DCVax-L. For patients with methylated MGMT (n = 131), mOS was 34.7 months from surgery, with a 3-year survival of 46.4%. As of this analysis, 223 patients are ≥ 30 months past their surgery date; 67 of these (30.0%) have lived ≥ 30 months and have a Kaplan-Meier (KM)-derived mOS of 46.5 months. 182 patients are ≥ 36 months past surgery; 44 of these (24.2%) have lived ≥ 36 months and have a KM-derived mOS of 88.2 months. A population of extended survivors (n = 100) with mOS of 40.5 months, not explained by known prognostic factors, will be analyzed further. Only 2.1% of ITT patients (n = 7) had a grade 3 or 4 adverse event that was deemed at least possibly related to the vaccine. Overall adverse events with DCVax were comparable to standard therapy alone. Conclusions: Addition of DCVax-L to standard therapy is feasible and safe in glioblastoma patients, and may extend survival.

Original languageEnglish (US)
Article number142
Number of pages1
JournalJournal of Translational Medicine
Volume16
Issue number1
DOIs
StatePublished - May 29 2018

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Phase III Clinical Trials
temozolomide
Glioblastoma
Dendritic Cells
Surgery
Vaccines
Survival
Chemoradiotherapy
Cross-Over Studies
Population
Radiotherapy
Therapeutics
Tumors
Disease-Free Survival
Survivors
Placebos
Recurrence

Keywords

  • Dendritic cell
  • Glioblastoma
  • Immunotherapy
  • Vaccine

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

First results on survival from a large Phase 3 clinical trial of an autologous dendritic cell vaccine in newly diagnosed glioblastoma. / Liau, Linda M.; Ashkan, Keyoumars; Tran, David D.; Campian, Jian L.; Trusheim, John E.; Cobbs, Charles S.; Heth, Jason A.; Salacz, Michael; Taylor, Sarah; D'Andre, Stacy D.; Iwamoto, Fabio M.; Dropcho, Edward J.; Moshel, Yaron A.; Walter, Kevin A.; Pillainayagam, Clement P.; Aiken, Robert; Chaudhary, Rekha; Goldlust, Samuel A.; Bota, Daniela A.; Duic, Paul; Grewal, Jai; Elinzano, Heinrich; Toms, Steven A.; Lillehei, Kevin O.; Mikkelsen, Tom; Walpert, Tobias; Abram, Steven R.; Brenner, Andrew; Brem, Steven; Ewend, Matthew G.; Khagi, Simon; Portnow, Jana; Kim, Lyndon J.; Loudon, William G.; Thompson, Reid C.; Avigan, David E.; Fink, Karen L.; Geoffroy, Francois J.; Lindhorst, Scott; Lutzky, Jose; Sloan, Andrew E.; Schackert, Gabriele; Krex, Dietmar; Meisel, Hans Jorg; Wu, Julian; Davis, Raphael P.; Duma, Christopher; Etame, Arnold B.; Mathieu, David; Kesari, Santosh; Piccioni, David; Westphal, Manfred; Baskin, David S.; New, Pamela Z.; Lacroix, Michel; May, Sven Axel; Pluard, Timothy J.; Tse, Victor; Green, Richard M.; Villano, John L.; Pearlman, Michael; Petrecca, Kevin; Schulder, Michael; Taylor, Lynne P.; Maida, Anthony E.; Prins, Robert M.; Cloughesy, Timothy F.; Mulholland, Paul; Bosch, Marnix L.

In: Journal of Translational Medicine, Vol. 16, No. 1, 142, 29.05.2018.

Research output: Contribution to journalArticle

Liau, LM, Ashkan, K, Tran, DD, Campian, JL, Trusheim, JE, Cobbs, CS, Heth, JA, Salacz, M, Taylor, S, D'Andre, SD, Iwamoto, FM, Dropcho, EJ, Moshel, YA, Walter, KA, Pillainayagam, CP, Aiken, R, Chaudhary, R, Goldlust, SA, Bota, DA, Duic, P, Grewal, J, Elinzano, H, Toms, SA, Lillehei, KO, Mikkelsen, T, Walpert, T, Abram, SR, Brenner, A, Brem, S, Ewend, MG, Khagi, S, Portnow, J, Kim, LJ, Loudon, WG, Thompson, RC, Avigan, DE, Fink, KL, Geoffroy, FJ, Lindhorst, S, Lutzky, J, Sloan, AE, Schackert, G, Krex, D, Meisel, HJ, Wu, J, Davis, RP, Duma, C, Etame, AB, Mathieu, D, Kesari, S, Piccioni, D, Westphal, M, Baskin, DS, New, PZ, Lacroix, M, May, SA, Pluard, TJ, Tse, V, Green, RM, Villano, JL, Pearlman, M, Petrecca, K, Schulder, M, Taylor, LP, Maida, AE, Prins, RM, Cloughesy, TF, Mulholland, P & Bosch, ML 2018, 'First results on survival from a large Phase 3 clinical trial of an autologous dendritic cell vaccine in newly diagnosed glioblastoma', Journal of Translational Medicine, vol. 16, no. 1, 142. https://doi.org/10.1186/s12967-018-1507-6
Liau, Linda M. ; Ashkan, Keyoumars ; Tran, David D. ; Campian, Jian L. ; Trusheim, John E. ; Cobbs, Charles S. ; Heth, Jason A. ; Salacz, Michael ; Taylor, Sarah ; D'Andre, Stacy D. ; Iwamoto, Fabio M. ; Dropcho, Edward J. ; Moshel, Yaron A. ; Walter, Kevin A. ; Pillainayagam, Clement P. ; Aiken, Robert ; Chaudhary, Rekha ; Goldlust, Samuel A. ; Bota, Daniela A. ; Duic, Paul ; Grewal, Jai ; Elinzano, Heinrich ; Toms, Steven A. ; Lillehei, Kevin O. ; Mikkelsen, Tom ; Walpert, Tobias ; Abram, Steven R. ; Brenner, Andrew ; Brem, Steven ; Ewend, Matthew G. ; Khagi, Simon ; Portnow, Jana ; Kim, Lyndon J. ; Loudon, William G. ; Thompson, Reid C. ; Avigan, David E. ; Fink, Karen L. ; Geoffroy, Francois J. ; Lindhorst, Scott ; Lutzky, Jose ; Sloan, Andrew E. ; Schackert, Gabriele ; Krex, Dietmar ; Meisel, Hans Jorg ; Wu, Julian ; Davis, Raphael P. ; Duma, Christopher ; Etame, Arnold B. ; Mathieu, David ; Kesari, Santosh ; Piccioni, David ; Westphal, Manfred ; Baskin, David S. ; New, Pamela Z. ; Lacroix, Michel ; May, Sven Axel ; Pluard, Timothy J. ; Tse, Victor ; Green, Richard M. ; Villano, John L. ; Pearlman, Michael ; Petrecca, Kevin ; Schulder, Michael ; Taylor, Lynne P. ; Maida, Anthony E. ; Prins, Robert M. ; Cloughesy, Timothy F. ; Mulholland, Paul ; Bosch, Marnix L. / First results on survival from a large Phase 3 clinical trial of an autologous dendritic cell vaccine in newly diagnosed glioblastoma. In: Journal of Translational Medicine. 2018 ; Vol. 16, No. 1.
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title = "First results on survival from a large Phase 3 clinical trial of an autologous dendritic cell vaccine in newly diagnosed glioblastoma",
abstract = "Background: Standard therapy for glioblastoma includes surgery, radiotherapy, and temozolomide. This Phase 3 trial evaluates the addition of an autologous tumor lysate-pulsed dendritic cell vaccine (DCVax{\circledR}-L) to standard therapy for newly diagnosed glioblastoma. Methods: After surgery and chemoradiotherapy, patients were randomized (2:1) to receive temozolomide plus DCVax-L (n = 232) or temozolomide and placebo (n = 99). Following recurrence, all patients were allowed to receive DCVax-L, without unblinding. The primary endpoint was progression free survival (PFS); the secondary endpoint was overall survival (OS). Results: For the intent-to-treat (ITT) population (n = 331), median OS (mOS) was 23.1 months from surgery. Because of the cross-over trial design, nearly 90{\%} of the ITT population received DCVax-L. For patients with methylated MGMT (n = 131), mOS was 34.7 months from surgery, with a 3-year survival of 46.4{\%}. As of this analysis, 223 patients are ≥ 30 months past their surgery date; 67 of these (30.0{\%}) have lived ≥ 30 months and have a Kaplan-Meier (KM)-derived mOS of 46.5 months. 182 patients are ≥ 36 months past surgery; 44 of these (24.2{\%}) have lived ≥ 36 months and have a KM-derived mOS of 88.2 months. A population of extended survivors (n = 100) with mOS of 40.5 months, not explained by known prognostic factors, will be analyzed further. Only 2.1{\%} of ITT patients (n = 7) had a grade 3 or 4 adverse event that was deemed at least possibly related to the vaccine. Overall adverse events with DCVax were comparable to standard therapy alone. Conclusions: Addition of DCVax-L to standard therapy is feasible and safe in glioblastoma patients, and may extend survival.",
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author = "Liau, {Linda M.} and Keyoumars Ashkan and Tran, {David D.} and Campian, {Jian L.} and Trusheim, {John E.} and Cobbs, {Charles S.} and Heth, {Jason A.} and Michael Salacz and Sarah Taylor and D'Andre, {Stacy D.} and Iwamoto, {Fabio M.} and Dropcho, {Edward J.} and Moshel, {Yaron A.} and Walter, {Kevin A.} and Pillainayagam, {Clement P.} and Robert Aiken and Rekha Chaudhary and Goldlust, {Samuel A.} and Bota, {Daniela A.} and Paul Duic and Jai Grewal and Heinrich Elinzano and Toms, {Steven A.} and Lillehei, {Kevin O.} and Tom Mikkelsen and Tobias Walpert and Abram, {Steven R.} and Andrew Brenner and Steven Brem and Ewend, {Matthew G.} and Simon Khagi and Jana Portnow and Kim, {Lyndon J.} and Loudon, {William G.} and Thompson, {Reid C.} and Avigan, {David E.} and Fink, {Karen L.} and Geoffroy, {Francois J.} and Scott Lindhorst and Jose Lutzky and Sloan, {Andrew E.} and Gabriele Schackert and Dietmar Krex and Meisel, {Hans Jorg} and Julian Wu and Davis, {Raphael P.} and Christopher Duma and Etame, {Arnold B.} and David Mathieu and Santosh Kesari and David Piccioni and Manfred Westphal and Baskin, {David S.} and New, {Pamela Z.} and Michel Lacroix and May, {Sven Axel} and Pluard, {Timothy J.} and Victor Tse and Green, {Richard M.} and Villano, {John L.} and Michael Pearlman and Kevin Petrecca and Michael Schulder and Taylor, {Lynne P.} and Maida, {Anthony E.} and Prins, {Robert M.} and Cloughesy, {Timothy F.} and Paul Mulholland and Bosch, {Marnix L.}",
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TY - JOUR

T1 - First results on survival from a large Phase 3 clinical trial of an autologous dendritic cell vaccine in newly diagnosed glioblastoma

AU - Liau, Linda M.

AU - Ashkan, Keyoumars

AU - Tran, David D.

AU - Campian, Jian L.

AU - Trusheim, John E.

AU - Cobbs, Charles S.

AU - Heth, Jason A.

AU - Salacz, Michael

AU - Taylor, Sarah

AU - D'Andre, Stacy D.

AU - Iwamoto, Fabio M.

AU - Dropcho, Edward J.

AU - Moshel, Yaron A.

AU - Walter, Kevin A.

AU - Pillainayagam, Clement P.

AU - Aiken, Robert

AU - Chaudhary, Rekha

AU - Goldlust, Samuel A.

AU - Bota, Daniela A.

AU - Duic, Paul

AU - Grewal, Jai

AU - Elinzano, Heinrich

AU - Toms, Steven A.

AU - Lillehei, Kevin O.

AU - Mikkelsen, Tom

AU - Walpert, Tobias

AU - Abram, Steven R.

AU - Brenner, Andrew

AU - Brem, Steven

AU - Ewend, Matthew G.

AU - Khagi, Simon

AU - Portnow, Jana

AU - Kim, Lyndon J.

AU - Loudon, William G.

AU - Thompson, Reid C.

AU - Avigan, David E.

AU - Fink, Karen L.

AU - Geoffroy, Francois J.

AU - Lindhorst, Scott

AU - Lutzky, Jose

AU - Sloan, Andrew E.

AU - Schackert, Gabriele

AU - Krex, Dietmar

AU - Meisel, Hans Jorg

AU - Wu, Julian

AU - Davis, Raphael P.

AU - Duma, Christopher

AU - Etame, Arnold B.

AU - Mathieu, David

AU - Kesari, Santosh

AU - Piccioni, David

AU - Westphal, Manfred

AU - Baskin, David S.

AU - New, Pamela Z.

AU - Lacroix, Michel

AU - May, Sven Axel

AU - Pluard, Timothy J.

AU - Tse, Victor

AU - Green, Richard M.

AU - Villano, John L.

AU - Pearlman, Michael

AU - Petrecca, Kevin

AU - Schulder, Michael

AU - Taylor, Lynne P.

AU - Maida, Anthony E.

AU - Prins, Robert M.

AU - Cloughesy, Timothy F.

AU - Mulholland, Paul

AU - Bosch, Marnix L.

PY - 2018/5/29

Y1 - 2018/5/29

N2 - Background: Standard therapy for glioblastoma includes surgery, radiotherapy, and temozolomide. This Phase 3 trial evaluates the addition of an autologous tumor lysate-pulsed dendritic cell vaccine (DCVax®-L) to standard therapy for newly diagnosed glioblastoma. Methods: After surgery and chemoradiotherapy, patients were randomized (2:1) to receive temozolomide plus DCVax-L (n = 232) or temozolomide and placebo (n = 99). Following recurrence, all patients were allowed to receive DCVax-L, without unblinding. The primary endpoint was progression free survival (PFS); the secondary endpoint was overall survival (OS). Results: For the intent-to-treat (ITT) population (n = 331), median OS (mOS) was 23.1 months from surgery. Because of the cross-over trial design, nearly 90% of the ITT population received DCVax-L. For patients with methylated MGMT (n = 131), mOS was 34.7 months from surgery, with a 3-year survival of 46.4%. As of this analysis, 223 patients are ≥ 30 months past their surgery date; 67 of these (30.0%) have lived ≥ 30 months and have a Kaplan-Meier (KM)-derived mOS of 46.5 months. 182 patients are ≥ 36 months past surgery; 44 of these (24.2%) have lived ≥ 36 months and have a KM-derived mOS of 88.2 months. A population of extended survivors (n = 100) with mOS of 40.5 months, not explained by known prognostic factors, will be analyzed further. Only 2.1% of ITT patients (n = 7) had a grade 3 or 4 adverse event that was deemed at least possibly related to the vaccine. Overall adverse events with DCVax were comparable to standard therapy alone. Conclusions: Addition of DCVax-L to standard therapy is feasible and safe in glioblastoma patients, and may extend survival.

AB - Background: Standard therapy for glioblastoma includes surgery, radiotherapy, and temozolomide. This Phase 3 trial evaluates the addition of an autologous tumor lysate-pulsed dendritic cell vaccine (DCVax®-L) to standard therapy for newly diagnosed glioblastoma. Methods: After surgery and chemoradiotherapy, patients were randomized (2:1) to receive temozolomide plus DCVax-L (n = 232) or temozolomide and placebo (n = 99). Following recurrence, all patients were allowed to receive DCVax-L, without unblinding. The primary endpoint was progression free survival (PFS); the secondary endpoint was overall survival (OS). Results: For the intent-to-treat (ITT) population (n = 331), median OS (mOS) was 23.1 months from surgery. Because of the cross-over trial design, nearly 90% of the ITT population received DCVax-L. For patients with methylated MGMT (n = 131), mOS was 34.7 months from surgery, with a 3-year survival of 46.4%. As of this analysis, 223 patients are ≥ 30 months past their surgery date; 67 of these (30.0%) have lived ≥ 30 months and have a Kaplan-Meier (KM)-derived mOS of 46.5 months. 182 patients are ≥ 36 months past surgery; 44 of these (24.2%) have lived ≥ 36 months and have a KM-derived mOS of 88.2 months. A population of extended survivors (n = 100) with mOS of 40.5 months, not explained by known prognostic factors, will be analyzed further. Only 2.1% of ITT patients (n = 7) had a grade 3 or 4 adverse event that was deemed at least possibly related to the vaccine. Overall adverse events with DCVax were comparable to standard therapy alone. Conclusions: Addition of DCVax-L to standard therapy is feasible and safe in glioblastoma patients, and may extend survival.

KW - Dendritic cell

KW - Glioblastoma

KW - Immunotherapy

KW - Vaccine

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DO - 10.1186/s12967-018-1507-6

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