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Cancer Immunology Research
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Clinical Trials of Cancer Immunotherapies

Abstract A013: Haploidentical stem cell transplantation and subsequent immunotherapy with antiGD2 antibody for patients with relapsed metastatic neuroblastoma

Peter Lang, Tim Flaadt, Martin Ebinger, Patrick Schlegel, Holger Lode, Ruth Ladenstein, Anne-Marie Lang, Peter Ambross, Juergen Schaefer, Joerg Fuchs, Hans Loibner, Wolfgang Schwinger and Rupert Handgretinger
Peter Lang
University Children's Hospital Tübingen, Tübingen, Germany; Children's University Hospital, Greifswald, Germany; St. Anna Chidren's Hospital, Vienna, Austria; APEIRON Biologics AG, Vienna, Austria; Children's University Hospital, Graz, Austria.
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Tim Flaadt
University Children's Hospital Tübingen, Tübingen, Germany; Children's University Hospital, Greifswald, Germany; St. Anna Chidren's Hospital, Vienna, Austria; APEIRON Biologics AG, Vienna, Austria; Children's University Hospital, Graz, Austria.
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Martin Ebinger
University Children's Hospital Tübingen, Tübingen, Germany; Children's University Hospital, Greifswald, Germany; St. Anna Chidren's Hospital, Vienna, Austria; APEIRON Biologics AG, Vienna, Austria; Children's University Hospital, Graz, Austria.
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Patrick Schlegel
University Children's Hospital Tübingen, Tübingen, Germany; Children's University Hospital, Greifswald, Germany; St. Anna Chidren's Hospital, Vienna, Austria; APEIRON Biologics AG, Vienna, Austria; Children's University Hospital, Graz, Austria.
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Holger Lode
University Children's Hospital Tübingen, Tübingen, Germany; Children's University Hospital, Greifswald, Germany; St. Anna Chidren's Hospital, Vienna, Austria; APEIRON Biologics AG, Vienna, Austria; Children's University Hospital, Graz, Austria.
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Ruth Ladenstein
University Children's Hospital Tübingen, Tübingen, Germany; Children's University Hospital, Greifswald, Germany; St. Anna Chidren's Hospital, Vienna, Austria; APEIRON Biologics AG, Vienna, Austria; Children's University Hospital, Graz, Austria.
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Anne-Marie Lang
University Children's Hospital Tübingen, Tübingen, Germany; Children's University Hospital, Greifswald, Germany; St. Anna Chidren's Hospital, Vienna, Austria; APEIRON Biologics AG, Vienna, Austria; Children's University Hospital, Graz, Austria.
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Peter Ambross
University Children's Hospital Tübingen, Tübingen, Germany; Children's University Hospital, Greifswald, Germany; St. Anna Chidren's Hospital, Vienna, Austria; APEIRON Biologics AG, Vienna, Austria; Children's University Hospital, Graz, Austria.
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Juergen Schaefer
University Children's Hospital Tübingen, Tübingen, Germany; Children's University Hospital, Greifswald, Germany; St. Anna Chidren's Hospital, Vienna, Austria; APEIRON Biologics AG, Vienna, Austria; Children's University Hospital, Graz, Austria.
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Joerg Fuchs
University Children's Hospital Tübingen, Tübingen, Germany; Children's University Hospital, Greifswald, Germany; St. Anna Chidren's Hospital, Vienna, Austria; APEIRON Biologics AG, Vienna, Austria; Children's University Hospital, Graz, Austria.
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Hans Loibner
University Children's Hospital Tübingen, Tübingen, Germany; Children's University Hospital, Greifswald, Germany; St. Anna Chidren's Hospital, Vienna, Austria; APEIRON Biologics AG, Vienna, Austria; Children's University Hospital, Graz, Austria.
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Wolfgang Schwinger
University Children's Hospital Tübingen, Tübingen, Germany; Children's University Hospital, Greifswald, Germany; St. Anna Chidren's Hospital, Vienna, Austria; APEIRON Biologics AG, Vienna, Austria; Children's University Hospital, Graz, Austria.
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Rupert Handgretinger
University Children's Hospital Tübingen, Tübingen, Germany; Children's University Hospital, Greifswald, Germany; St. Anna Chidren's Hospital, Vienna, Austria; APEIRON Biologics AG, Vienna, Austria; Children's University Hospital, Graz, Austria.
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DOI: 10.1158/2326-6074.CRICIMTEATIAACR18-A013 Published February 2019
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Abstracts: Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; September 30 - October 3, 2018; New York, NY

Abstract

Background: Pediatric patients with relapsed metastatic neuroblastomas have a poor prognosis and additional strategies are needed. We present results of a phase I/II-trial with subsequent immunotherapy with an anti-GD2mAb (CH14.18/CHO) after HLA-mismatched, haploidentical stem cell transplantation (SCT). Methods: T- and B-cell depleted stem cells from parental donors were used in combination with melphalan 140mg/m², thiotepa 10mg/kg, fludarabin 160mg/m² and ATG-F. CH14.18/CHOmAb was started on day 60-180 post-transplant: 6 cycles with 20mg/m²/day x 5; in cycles 4-6, 1x106 U/m² Interleukin 2 was given additionally. Disease status was evaluated with whole body MRI, MIBG scan and MRD detection in bone marrow aspirates. Primary endpoint was success of treatment, defined as a patient receiving the full protocol treatment, still alive 180 days after end of treatment without progression/unacceptable toxicity or severe GvHD. Results: 56 patients with 1st or ≥2nd metastatic relapse were enrolled. Disease status prior to antibody infusions was: CR (n=19), PR (n=31), mixed (n=6). 41% of patients with measurable tumor burden responded and reached CR after treatment. 90% of patients with initial CR could maintain this status. In total, success of treatment was observed in 60%. 3-year OS and EFS was 58% and 45%, respectively. Causes of death were: progression/relapse (25%) or TRM (7%). Factors of influence on EFS were (1) remission status prior to SCT (with CR, PR or mixed response resulting in 70%, 45% and 11% 3yEFS) and (2) bone marrow involvement prior to CH14.18 treatment (no MRD detectable: 60% 3yEFS vs. any MRD detectable: 20% 3yEFS). Frequent side effects were pain, fever, CRP elevation; rare side effects comprised SIRS/capillary leak syndrome, seizures, accommodation disturbances. Transient acute severe GvHD occurred in 1 patient. Conclusions: CH14.18/CHO infusions after haploidentical SCT are feasible with acceptable toxicity. Our results suggest an antitumor effect of the new, donor-derived immune system in combination with CH14.18 treatment.

Citation Format: Peter Lang, Tim Flaadt, Martin Ebinger, Patrick Schlegel, Holger Lode, Ruth Ladenstein, Anne-Marie Lang, Peter Ambross, Juergen Schaefer, Joerg Fuchs, Hans Loibner, Wolfgang Schwinger, Rupert Handgretinger. Haploidentical stem cell transplantation and subsequent immunotherapy with antiGD2 antibody for patients with relapsed metastatic neuroblastoma [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr A013.

  • ©2019 American Association for Cancer Research.
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Cancer Immunology Research: 7 (2 Supplement)
February 2019
Volume 7, Issue 2 Supplement
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Abstract A013: Haploidentical stem cell transplantation and subsequent immunotherapy with antiGD2 antibody for patients with relapsed metastatic neuroblastoma
Peter Lang, Tim Flaadt, Martin Ebinger, Patrick Schlegel, Holger Lode, Ruth Ladenstein, Anne-Marie Lang, Peter Ambross, Juergen Schaefer, Joerg Fuchs, Hans Loibner, Wolfgang Schwinger and Rupert Handgretinger
Cancer Immunol Res February 1 2019 (7) (2 Supplement) A013; DOI: 10.1158/2326-6074.CRICIMTEATIAACR18-A013

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Abstract A013: Haploidentical stem cell transplantation and subsequent immunotherapy with antiGD2 antibody for patients with relapsed metastatic neuroblastoma
Peter Lang, Tim Flaadt, Martin Ebinger, Patrick Schlegel, Holger Lode, Ruth Ladenstein, Anne-Marie Lang, Peter Ambross, Juergen Schaefer, Joerg Fuchs, Hans Loibner, Wolfgang Schwinger and Rupert Handgretinger
Cancer Immunol Res February 1 2019 (7) (2 Supplement) A013; DOI: 10.1158/2326-6074.CRICIMTEATIAACR18-A013
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