Poster Presentation Advances in Neuroblastoma Research Congress 2016

Interleukin-2 adds toxicity to long term infusion treatment regimen of ch14.18/CHO antibody without measurable additional activity in relapsed/refractory neuroblastoma patients. (#217)

Holger Lode 1 , Nikolai Siebert 1 , Christin Eger 1 , Evelyne Janzek 2 , Hans Loibner 2 , Ruth Ladenstein 3
  1. University Medicine Greifswald, Greifswald, Germany
  2. Apeiron Biologics, Vienna, Austria
  3. Children's Cancer Research Institute, Vienna, Austria

Background: Long-term infusion (LTI) emerges as a promising new delivery method of ch14.18/CHO for relapsed/refractory neuroblastoma patients. The role of concomitant treatment with scIL2 is unclear in this setting.

Methods: Pts (74) were treated with 5 cycles of LTI with 100 mg/m2 ch14.18/CHO (d8-17) combined with 6x106 IU/m2 sc IL-2 (d1-5; 8-12) (53 Pts) and without IL2 (21Pts) in a single center program. Surrogate parameters for activity and pain toxicity were determined using complement dependent cell mediated cytotoxicity (CDC), the whole blood cytotoxicity test (WBT) (d1, 8, 15) and analysis of the intravenous (iv) morphine usage (d8-17).

Results: In CDC and WBT assays, GD2 specific killing of neuroblastoma cells was found in all patients and cycles. The cytotoxic activity in base line samples preceding ch14.18/CHO applications increased over cycles, indicating persistent lytic activity over the entire treatment period of 6 months. This effect GD2 specific and was inhibited by anti-idiotypic antibody ganglidiomab. Interestingly, there was no difference cytotoxic activity at any time point between patients treated with or without IL2.

Analysis of iv morphine usage in cycle 1 of patients treated in combination with scIL2 revealed a cumulative dose of 2.5 mg/kg/cycle in contrast to patients treated with ch14.18/CHO only (1 mg/kg/cycle). This corresponds to a >60% increase of the pain toxicity by additional scIL2 treatment. Reduction of iv morphine usage in subsequent treatment cycles was observed in both cohorts. However, in patients treated without additional scIL2, 0% of patients required iv morphine in cycles 3 or greater in contrast to 29% in the scIL2 combination group.

Conclusion: Neither the surrogate WBT activity parameter nor the higher pain toxicity profile support the combined treatment of antibody with IL2 in above pilot studies.  Ongoing SIOPEN trials (EudraCT 2009-018077-31; EudraCT2006-001489-17) randomizing LTI ch14.18/CHO ± scIL2 in front line and relapsed/refractory patients will clarify the optimal approach.