Tolerability, response and outcome of high-risk neuroblastoma patients treated with long-term infusion of anti-GD2 antibody ch14.18/CHO

Ina Mueller, Karoline Ehlert, Stefanie Endres, Lena Pill, Nikolai Siebert, Silke Kietz, Penelope Brock, Alberto Garaventa, Dominique Valteau-Couanet, Evelyne Janzek, Norbert Hosten, Andreas Zinke, Winfried Barthlen, Emine Varol, Hans Loibner, Ruth Ladenstein, Holger N Lode

Research output: Contribution to journalArticle

Abstract

Immunotherapy with short term infusion (STI) of monoclonal anti-GD2 antibody (mAb) ch14.18 (4 × 25 mg/m2/d; 8-20 h) in combination with cytokines and 13-cis retinoic acid (RA) prolonged survival in high-risk neuroblastoma (NB) patients. Here, we investigated long-term infusion (LTI) of ch14.18 produced in Chinese hamster ovary cells (ch14.18/CHO; 10 × 10 mg/m2; 24 h) in combination with subcutaneous (s.c.) interleukin-2 (IL-2) in a single center program and report clinical response, toxicity and survival. Fifty-three high-risk NB patients received up to 6 cycles of 100 mg/m2 ch14.18/CHO (d8-17) as LTI combined with 6 × 106 IU/m2 s.c. IL-2 (d1-5; 8-12) and 160 mg/m2 oral RA (d19-32). Pain toxicity was documented with validated pain scores and intravenous (i.v.) morphine usage. Response was assessed in 37/53 evaluable patients following International Neuroblastoma Risk Group criteria. Progression-free (PFS) and overall survival (OS) was analyzed by the Kaplan-Meier method and compared to a matched historical control group from the database of AIEOP, the "Italian Pediatric Ematology and Oncology Association". LTI of ch14.18/CHO showed acceptable toxicity profile indicated by low pain scores, reduced i.v. morphine usage and low frequency of Grade ≥3 adverse events that allowed outpatient treatment. We observed a best response rate of 40.5% (15/37; 5 CR, 10 PR), 4-year (4 y) PFS of 33.1% (observation 0.1- 4.9 y, mean: 2.2 y) and a 4 y OS of 47.7% (observation 0.27 - 5.20 y, mean: 3.6 y). Survival of the entire cohort (53/53) and the relapsed patients (29/53) was significantly improved compared to historical controls. LTI of ch14.18/CHO thus shows an acceptable toxicity profile, objective clinical responses and a strong signal of clinical efficacy in NB patients.

Original languageEnglish
Pages (from-to)55-61
Number of pages7
JournalmAbs
Volume10
Issue number1
DOIs
Publication statusPublished - Jan 2018

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Keywords

  • Adolescent
  • Adult
  • Antibodies, Monoclonal/administration & dosage
  • Antineoplastic Agents, Immunological/administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols/adverse effects
  • Child
  • Child, Preschool
  • Drug Administration Schedule
  • Female
  • Gangliosides/immunology
  • Humans
  • Immunotherapy/adverse effects
  • Infant
  • Infusions, Intravenous
  • Interleukin-2/administration & dosage
  • Isotretinoin/administration & dosage
  • Male
  • Neuroblastoma/immunology
  • Progression-Free Survival
  • Time Factors
  • Treatment Outcome
  • Young Adult

Cite this

Mueller, I., Ehlert, K., Endres, S., Pill, L., Siebert, N., Kietz, S., Brock, P., Garaventa, A., Valteau-Couanet, D., Janzek, E., Hosten, N., Zinke, A., Barthlen, W., Varol, E., Loibner, H., Ladenstein, R., & Lode, H. N. (2018). Tolerability, response and outcome of high-risk neuroblastoma patients treated with long-term infusion of anti-GD2 antibody ch14.18/CHO. mAbs, 10(1), 55-61. https://doi.org/10.1080/19420862.2017.1402997