Interleukin 2 plus anti-GD2 immunotherapy: helpful or harmful?

Both interleukin 2 (IL-2) and granulocyte-macrophage colony-stimulating factor (GM-CSF) increase antibody-dependent and complement-dependent cytotoxicity with anti-GD2.3 A chimeric anti-GD2 antibody, ch14.18 (dinutuximab), was tested in pilot trials with IL-2 and GM-CSF in the setting of minimal residual disease after autologous haemopoietic stem-cell transplant, showing tolerability.4 Subsequently, a Children's Oncology Group (COG) phase 3 trial5 reported significant improvement in 2-year event-free survival after myeloablative therapy using isotretinoin with five cycles of ch14.18 with GM-CSF and IL-2 compared with isotretinoin alone, leading to US Food and Drug Administration approval of this immunotherapy regimen. In The Lancet Oncology, Ruth Ladenstein and colleagues report results from the SIOP Europe Neuroblastoma (SIOPEN) group randomised trial, which was designed to determine whether IL-2 was necessary for the efficacy of dinutuximab beta given with standard isotretinoin after high-dose chemotherapy with autologous haemopoietic stem-cell transplant.6 This international trial of 406 patients, stratified by myeloablative regimen and country, yielded nearly identical 3-year event-free survival of 56% (95% CI 49–63) and 60% (53–66) in the two groups (p=0·76). Furthermore, the overall event-free survival was similar to that of a recent COG immunotherapy safety trial7 that reported a 3-year event-free survival of 67%.7 One important caveat is that only 62% of the patients randomly assigned to the IL-2 group received their assigned therapy, mainly because of toxicity, compared with 87% of patients receiving dinutuximab alone. [...]the absence of improved outcome might be attributed to under-dosing.