Toxicity and outcome of anti-GD2 antibody ch14.18/CHO in front-line, high-risk patients with neuroblastoma: Final results of the phase III immunotherapy randomisation (HR-NBL1/SIOPEN trial).

10500 Background: Dinutuximab (ch14.18/SP2/0) in combination with cytokines (IL2 and GM-CSF) resulted in a survival benefit in high risk neuroblastoma (NB) patients (2y EFS 66%±5%, A.Yu, NEJM, 2010). The role of cytokines in this context remains unclear. We investigated the role of scIL2 for immunotherapy with ch14.18/CHO in a prospective randomized Phase III clinical trial. Methods: 406 high risk NB patient (pts) (stage 4 ≥ 1y; stage 4 < 1y with MYCN amplification (MNA); stage 2,3 0-21y with MNA) were randomized (R2 of HR-NBL1/SIOPEN; APN311-302; EudraCT:2006-001489-17). Pretreatment consisted of high intensity induction followed by autologous stem cell transplantation as well as local therapy. Pts were randomized to receive immunotherapy (IT) of either 100mg/m² ch14.18/CHO (d8-12) as 5 daily 8-hour short term infusions (STI) alone (STI-A) or combined with 6x106IU/m2 scIL2 (d1-5;8-12) (STI-B) for a total of 5 cycles. All patients received 6 cycles of oral 13-cis-RA (160mg/m2,d19-32). Results: We observed 3y EFS and OS rates for 206 pts treated by STI-A of 60±4% and 66±4%. 200 pts treated by STI-B showed 3y EFS and OS rates of 57±4% and 65±4%. The difference between both arms was statistically not significant (NS). A subgroup analysis according to response to induction revealed 3y EFS rates of 68±5% and 65±5% in patients treated in CR with regimen STI-A and STI-B, respectively (NS). The 3y EFS rates in pts with VGPR or PR at the time of randomization were expectedly lower at 46±6% and 53±6% for STI-A and STI-B, respectively (NS). Toxicity analysis indicated a higher rate of early termination in STI-B (44%) compared to STI-A (18%). Lansky performance status of ≤ 30% was found in 17% of STI-A- and 39% STI-B-pts (p < 0.001). CTC-grade 3&4 allergic reactions in STI-A- and STI-B-cohorts were 9% and 20% ( < 0.001). Incidence of capillary leak and CTC-grade 3&4 fever is significantly lower in the STI-A (1% and 14%) compared to the STI-B cohort (9% and 40%). Conclusions: Outcome data of frontline patients treated with ch14.18/CHO are highly encouraging. However, survival and toxicity analysis indicated no benefit of co-treatment with scIL2 in this setting. Clinical trial information: NCT01704716.