%0 Generic %A Ozkaynak, M. Fevzi %A Gilman, Andrew L. %A B. London, Wendy %A Naranjo, Arlene %A B. Diccianni, Mitchell %A Tenney, Sheena C. %A Smith, Malcolm %A Messer, Karen S. %A Seeger, Robert %A Patrick Reynolds, C. %A Smith, L. Mary %A Shulkin, Barry L. %A Parisi, Marguerite %A M. Maris, John %A Park, Julie R. %A Sondel, Paul M. %A L. Yu, Alice %D 2018 %T table_1_A Comprehensive Safety Trial of Chimeric Antibody 14.18 With GM-CSF, IL-2, and Isotretinoin in High-Risk Neuroblastoma Patients Following Myeloablative Therapy: Children’s Oncology Group Study ANBL0931.PDF %U https://frontiersin.figshare.com/articles/dataset/table_1_A_Comprehensive_Safety_Trial_of_Chimeric_Antibody_14_18_With_GM-CSF_IL-2_and_Isotretinoin_in_High-Risk_Neuroblastoma_Patients_Following_Myeloablative_Therapy_Children_s_Oncology_Group_Study_ANBL0931_PDF/6586289 %R 10.3389/fimmu.2018.01355.s002 %2 https://frontiersin.figshare.com/ndownloader/files/12073271 %K neuroblastoma %K immunotherapy %K anti-GD2 chimeric antibody %K cytokines %K safety %K cytokine biomarkers %X Purpose

A phase 3 randomized study (COG ANBL0032) demonstrated significantly improved outcome by adding immunotherapy with ch14.18 antibody to isotretinoin as post-consolidation therapy for high-risk neuroblastoma (NB). This study, ANBL0931, was designed to collect FDA-required safety/toxicity data to support FDA registration of ch14.18.

Experimental design

Newly diagnosed high-risk NB patients who achieved at least a partial response to induction therapy and received myeloablative consolidation with stem cell rescue were enrolled to receive six courses of isotretinoin with five concomitant cycles of ch14.18 combined with GM-CSF or IL2. Ch14.18 infusion time was 10–20 h per dose. Blood was collected for cytokine analysis and its association with toxicities and outcome.

Results

Of 105 patients enrolled, five patients developed protocol-defined unacceptable toxicities. The most common grade ≥ 3 non-hematologic toxicities of immunotherapy for cycles 1–5, respectively, were neuropathic pain (41, 28, 22, 31, 24%), hypotension (10, 17, 4, 14, 8%), allergic reactions (ARs) (3, 10, 5, 7, 2%), capillary leak syndrome (1, 4, 0, 2, 0%), and fever (21, 59, 6, 32, 5%). The 3-year event-free survival and overall survival were 67.6 ± 4.8% and 79.1 ± 4.2%, respectively. AR during course 1 was associated with elevated serum levels of IL-1Ra and IFNγ, while severe hypotension during this course was associated with low IL5 and nitrate. Higher pretreatment CXCL9 level was associated with poorer event-free survival (EFS).

Conclusion

This study has confirmed the significant, but manageable treatment-related toxicities of this immunotherapy and identified possible cytokine biomarkers associated with select toxicities and outcome. EFS and OS appear similar to that previously reported on ANBL0032.

%I Frontiers