Adjuvant immunotherapy to improve outcome in high-risk pediatric sarcomas

Melinda S. Merchant, Donna Bernstein, Martha Amoako, Kristin Baird, Thomas A. Fleisher, Michel Morre, Seth M. Steinberg, Marianna Sabatino, Dave F. Stroncek, Aradhana M. Venkatasan, Bradford J. Wood, Matthew Wright, Hua Zhang, Crystal L. Mackall

Research output: Contribution to journalArticle

Abstract

Purpose: Patients with metastatic or relapsed pediatric sarcomas receive cytotoxic regimens that induce high remission rates associated with profound lymphocyte depletion, but ultimately few survive long term. We administered adjuvant immunotherapy to patients with metastatic and recurrent pediatric sarcomas in an effort to improve outcomes. Experimental Design: Mononuclear cells were collected via apheresis, and tumor lysate was acquired via percutaneous biopsy at enrollment. Participants received standard antineoplastic therapy, followed by autologous lymphocytes, tumor lysate/keyhole limpet hemocyanin-pulsed dendritic cell vaccinations ± recombinant human IL7. Primary outcomes were toxicity and vaccine responses. Secondary outcomes were immune reconstitution, event-free survival, and overall survival (OS). Results: Forty-three patients enrolled and 29 received immunotherapy. The regimen was well tolerated. Intent-to-treat analysis demonstrated 5-year OS of 51% with significant differences based upon histologic group (63% vs. 0% for Ewing/rhabdomyosarcoma vs. other sarcomas) and response to standard therapy (74% no residual disease vs. 0% residual disease). Five-year intent-to-treat OS of patients with newly diagnosed metastatic Ewing/rhabdomyosarcoma was 77%, higher than previously reported in this population and higher than observed in a similar group treated with an earlier adjuvant immunotherapy regimen (25% 5-year OS). T-cell responses to autologous tumor lysate were identified in 62% of immunotherapy recipients, and survival was higher in those patients (73% 5-year OS with vs. 37% without immune response, P = 0.017). Immune reconstitution, measured by CD4 count recovery, was significantly enhanced in subjects treated with recombinant human IL7. Conclusions: Adjuvant immunotherapy may improve survival in patients with metastatic pediatric sarcoma.

Original languageEnglish (US)
Pages (from-to)3182-3191
Number of pages10
JournalClinical Cancer Research
Volume22
Issue number13
DOIs
StatePublished - Jul 1 2016
Externally publishedYes

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Sarcoma
Immunotherapy
Pediatrics
Survival
Interleukin-7
Rhabdomyosarcoma
Lymphocyte Depletion
Neoplasms
Blood Component Removal
CD4 Lymphocyte Count
Antineoplastic Agents
Dendritic Cells
Disease-Free Survival
Vaccination
Research Design
Vaccines
Lymphocytes
T-Lymphocytes
Biopsy
Therapeutics

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Merchant, M. S., Bernstein, D., Amoako, M., Baird, K., Fleisher, T. A., Morre, M., ... Mackall, C. L. (2016). Adjuvant immunotherapy to improve outcome in high-risk pediatric sarcomas. Clinical Cancer Research, 22(13), 3182-3191. https://doi.org/10.1158/1078-0432.CCR-15-2550

Adjuvant immunotherapy to improve outcome in high-risk pediatric sarcomas. / Merchant, Melinda S.; Bernstein, Donna; Amoako, Martha; Baird, Kristin; Fleisher, Thomas A.; Morre, Michel; Steinberg, Seth M.; Sabatino, Marianna; Stroncek, Dave F.; Venkatasan, Aradhana M.; Wood, Bradford J.; Wright, Matthew; Zhang, Hua; Mackall, Crystal L.

In: Clinical Cancer Research, Vol. 22, No. 13, 01.07.2016, p. 3182-3191.

Research output: Contribution to journalArticle

Merchant, MS, Bernstein, D, Amoako, M, Baird, K, Fleisher, TA, Morre, M, Steinberg, SM, Sabatino, M, Stroncek, DF, Venkatasan, AM, Wood, BJ, Wright, M, Zhang, H & Mackall, CL 2016, 'Adjuvant immunotherapy to improve outcome in high-risk pediatric sarcomas', Clinical Cancer Research, vol. 22, no. 13, pp. 3182-3191. https://doi.org/10.1158/1078-0432.CCR-15-2550
Merchant MS, Bernstein D, Amoako M, Baird K, Fleisher TA, Morre M et al. Adjuvant immunotherapy to improve outcome in high-risk pediatric sarcomas. Clinical Cancer Research. 2016 Jul 1;22(13):3182-3191. https://doi.org/10.1158/1078-0432.CCR-15-2550
Merchant, Melinda S. ; Bernstein, Donna ; Amoako, Martha ; Baird, Kristin ; Fleisher, Thomas A. ; Morre, Michel ; Steinberg, Seth M. ; Sabatino, Marianna ; Stroncek, Dave F. ; Venkatasan, Aradhana M. ; Wood, Bradford J. ; Wright, Matthew ; Zhang, Hua ; Mackall, Crystal L. / Adjuvant immunotherapy to improve outcome in high-risk pediatric sarcomas. In: Clinical Cancer Research. 2016 ; Vol. 22, No. 13. pp. 3182-3191.
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abstract = "Purpose: Patients with metastatic or relapsed pediatric sarcomas receive cytotoxic regimens that induce high remission rates associated with profound lymphocyte depletion, but ultimately few survive long term. We administered adjuvant immunotherapy to patients with metastatic and recurrent pediatric sarcomas in an effort to improve outcomes. Experimental Design: Mononuclear cells were collected via apheresis, and tumor lysate was acquired via percutaneous biopsy at enrollment. Participants received standard antineoplastic therapy, followed by autologous lymphocytes, tumor lysate/keyhole limpet hemocyanin-pulsed dendritic cell vaccinations ± recombinant human IL7. Primary outcomes were toxicity and vaccine responses. Secondary outcomes were immune reconstitution, event-free survival, and overall survival (OS). Results: Forty-three patients enrolled and 29 received immunotherapy. The regimen was well tolerated. Intent-to-treat analysis demonstrated 5-year OS of 51{\%} with significant differences based upon histologic group (63{\%} vs. 0{\%} for Ewing/rhabdomyosarcoma vs. other sarcomas) and response to standard therapy (74{\%} no residual disease vs. 0{\%} residual disease). Five-year intent-to-treat OS of patients with newly diagnosed metastatic Ewing/rhabdomyosarcoma was 77{\%}, higher than previously reported in this population and higher than observed in a similar group treated with an earlier adjuvant immunotherapy regimen (25{\%} 5-year OS). T-cell responses to autologous tumor lysate were identified in 62{\%} of immunotherapy recipients, and survival was higher in those patients (73{\%} 5-year OS with vs. 37{\%} without immune response, P = 0.017). Immune reconstitution, measured by CD4 count recovery, was significantly enhanced in subjects treated with recombinant human IL7. Conclusions: Adjuvant immunotherapy may improve survival in patients with metastatic pediatric sarcoma.",
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AU - Merchant, Melinda S.

AU - Bernstein, Donna

AU - Amoako, Martha

AU - Baird, Kristin

AU - Fleisher, Thomas A.

AU - Morre, Michel

AU - Steinberg, Seth M.

AU - Sabatino, Marianna

AU - Stroncek, Dave F.

AU - Venkatasan, Aradhana M.

AU - Wood, Bradford J.

AU - Wright, Matthew

AU - Zhang, Hua

AU - Mackall, Crystal L.

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N2 - Purpose: Patients with metastatic or relapsed pediatric sarcomas receive cytotoxic regimens that induce high remission rates associated with profound lymphocyte depletion, but ultimately few survive long term. We administered adjuvant immunotherapy to patients with metastatic and recurrent pediatric sarcomas in an effort to improve outcomes. Experimental Design: Mononuclear cells were collected via apheresis, and tumor lysate was acquired via percutaneous biopsy at enrollment. Participants received standard antineoplastic therapy, followed by autologous lymphocytes, tumor lysate/keyhole limpet hemocyanin-pulsed dendritic cell vaccinations ± recombinant human IL7. Primary outcomes were toxicity and vaccine responses. Secondary outcomes were immune reconstitution, event-free survival, and overall survival (OS). Results: Forty-three patients enrolled and 29 received immunotherapy. The regimen was well tolerated. Intent-to-treat analysis demonstrated 5-year OS of 51% with significant differences based upon histologic group (63% vs. 0% for Ewing/rhabdomyosarcoma vs. other sarcomas) and response to standard therapy (74% no residual disease vs. 0% residual disease). Five-year intent-to-treat OS of patients with newly diagnosed metastatic Ewing/rhabdomyosarcoma was 77%, higher than previously reported in this population and higher than observed in a similar group treated with an earlier adjuvant immunotherapy regimen (25% 5-year OS). T-cell responses to autologous tumor lysate were identified in 62% of immunotherapy recipients, and survival was higher in those patients (73% 5-year OS with vs. 37% without immune response, P = 0.017). Immune reconstitution, measured by CD4 count recovery, was significantly enhanced in subjects treated with recombinant human IL7. Conclusions: Adjuvant immunotherapy may improve survival in patients with metastatic pediatric sarcoma.

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