Murine Anti-GD2 Monoclonal Antibody 3F8 Combined With Granulocyte-Macrophage Colony-Stimulating Factor and 13-<i>Cis</i>-Retinoic Acid in High-Risk Patients With Stage 4 Neuroblastoma in First Remission

Cheung, Nai‐Kong V.; Cheung, Irene Y.; Kushner, Brian H.; Ostrovnaya, Irina; Chamberlain, Elizabeth; Krämer, Kim; Modak, Shakeel

doi:10.1200/jco.2011.41.3807

Cited by 225 publications

(345 citation statements)

References 46 publications

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“…Early response of minimal residual disease (MRD) in BM was a significantly favorable prognostic factor for 3F8 used to consolidate first complete/very good partial remission (CR/VGPR). 23 In successive trials, 5-year PFS improved from 44% with 3F8 alone to 62% with 3F8 plus GM-CSF, results that underscore the antineoplastic advantage of GM-CSF activation of myeloid effectors. 21,23,29 We now report the first study centered on anti-G D2 mAb plus GM-CSF for consolidation of second or later CR/VGPR.…”

Section: Introductionmentioning

confidence: 92%

“…23 In successive trials, 5-year PFS improved from 44% with 3F8 alone to 62% with 3F8 plus GM-CSF, results that underscore the antineoplastic advantage of GM-CSF activation of myeloid effectors. 21,23,29 We now report the first study centered on anti-G D2 mAb plus GM-CSF for consolidation of second or later CR/VGPR. In fact, to our knowledge no prior report has presented outcome data with any kind of therapy for HR-NB patients in second or later CR/VGPR.…”

Section: Introductionmentioning

confidence: 92%

“…Although the ability to mount HAMA has been correlated with favorable outcome, 23 the presence of HAMA could accelerate blood clearance and limit the 3F8 drug effect, therefore 3F8 treatments were deferred until the HAMA titer became negative. After meeting the study's target aim for 2-year PFS using only 3F8/GM-CSF plus isotretinoin, the protocol was amended such that HAMA-positive patients could receive rituximab with or without outpatient maintenance chemotherapy.…”

Section: Discussionmentioning

confidence: 99%

“…As previously described in detail, 20,21,23 3F8/GM-CSF had manageable toxicities, therefore treatment was administered outpatient and 3F8 dosage was never reduced. Common side effects associated with 3F8 in the 451 cycles administered in this study were grade 2 generalized pain and urticaria.…”

Section: Toxicitymentioning

confidence: 99%

“…11,[13][14][15][16][17] The murine IgG3 anti-G D2 mAb 3F8 localizes selectively to NB. 18 In Phase II studies [19][20][21] and in the adjuvant setting, 22,23 3F8 caused pain and urticaria without delayed toxicities. Immunosuppressive chemotherapy prevented early emergence of human anti-mouse antibody (HAMA).…”

Section: Introductionmentioning

confidence: 99%

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Prolonged progression-free survival after consolidating second or later remissions of neuroblastoma with Anti-G_D2immunotherapy and isotretinoin: a prospective Phase II study

et al. 2015

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Relapse of high-risk neuroblastoma (HR-NB) is deemed invariably fatal yet increasing numbers of HR-NB patients achieve a second complete/very good partial remission (CR/VGPR), hence the urgency to find a successful consolidative therapy. Identifying efficacy in patients without assessable disease, however, is problematic. We report the first study providing outcome data for this group of patients with poor prognosis. To prevent another relapse, HR-NB patients in second or later CR/VGPR received the anti-G D2 murine antibody 3F8 plus granulocyte-macrophage colony-stimulating factor plus isotretinoin in a Phase II trial. Upon meeting the target aim for progression-free survival (PFS) in the initial cohort of 33 patients, the trial was amended to allow patients who developed human anti-mouse antibody (HAMA) to receive rituximab to ablate HAMA with or without low-dose maintenance chemotherapy until immunotherapy could resume. For the total of 101 study patients, 5-year PFS and overall survival (OS) rates were 33% § 5% and 48% § 5%, respectively. Among the 33 long-term progression-free survivors, 19 had MYCN amplification, 19 had previously received anti-G D2 immunotherapy plus isotretinoin (as first-line therapy), and 15 never received maintenance chemotherapy. In a multivariate analysis of prognostic factors, only absence of minimal residual disease in bone marrow after 2 cycles of immunotherapy and before initiation of isotretinoin or anti-HAMA therapy was significantly favorable for both PFS and OS. Therefore, long-term PFS is possible for HR-NB patients who achieve at least a second CR/VGPR and receive consolidation that includes anti-G D2 immunotherapy plus isotretinoin, even if the patients received these biological treatments before relapse. Results from this prospective study will aid in the development of future Phase II studies for this growing ultra high-risk patient population.

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Section: Introductionmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Toxicitymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Prolonged progression-free survival after consolidating second or later remissions of neuroblastoma with Anti-G_D2immunotherapy and isotretinoin: a prospective Phase II study

et al. 2015

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Humanized 3F8 Anti-G_D2Monoclonal Antibody Dosing With Granulocyte-Macrophage Colony-Stimulating Factor in Patients With Resistant Neuroblastoma

et al. 2018

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IMPORTANCE Chimeric and murine anti-G D2 antibodies are active against neuroblastoma, but the development of neutralizing antibodies can compromise efficacy. To decrease immunogenicity, hu3F8, a humanized anti-G D2 antibody, was constructed. OBJECTIVE To find the maximum-tolerated dose of hu3F8 with granulocyte-macrophage colony-stimulating factor. DESIGN, SETTING, AND PARTICIPANTS This phase 1 clinical trial used a 3 + 3 dose-escalation design in a single referral center (Memorial

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Effect of Oral β-Glucan on Antibody Response to Ganglioside Vaccine in Patients With High-Risk Neuroblastoma

et al. 2023

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ImportanceAmong patients with high-risk relapsed metastatic neuroblastoma, oral β-glucan adjuvant during GD2/GD3 ganglioside vaccine boost has stimulated IgG antibody response, which was associated with improved survival; however, the effectiveness of oral β-glucan during the vaccine priming phase remains unproven.ObjectiveTo isolate the adjuvant effect of oral β-glucan on antibody response to GD2/GD3 ganglioside vaccine in patients with high-risk neuroblastoma.Design, Setting, and ParticipantsIn this phase 2 randomized clinical trial, enrolled patients with high-risk neuroblastoma were randomized to 2 groups to receive the GD2/GD3 vaccine at a large cancer center in a major metropolitan area from October 2018 to September 2020. Data were analyzed from October 7, 2021, to February 28, 2022.InterventionsEligible patients receiving GD2/GD3 vaccine were randomly assigned to group 1 (n = 54) to receive no β-glucan or group 2 (n = 53) to receive an oral β-glucan regimen during the first 5 weeks of vaccine priming. From week 6 onwards, all 107 patients received oral β-glucan during vaccine boost for 1 year or until disease progression.Main Outcomes and MeasuresPrimary end point was comparison of anti-GD2 IgG1 response before vaccine injection 6 (week 32) in group 1 vs group 2. Seroconversion rate and the association of antibody titer with β-glucan receptor dectin-1 single nucleotide polymorphism (SNP) rs3901533 were also assessed.ResultsIn all, 107 patients with high-risk neuroblastoma were randomized to the 2 groups: 54 patients (median [range] age, 5.2 [1.0-17.3] years; 28 [52%] male and 26 [48%] female) in group 1; and 53 patients (median [range] age, 6.2 [1.9-18.4] years; 25 [47%] male and 28 [53%] female) in group 2; both groups were also comparable in their first remission status at study entry (70% vs 70%). Adding oral β-glucan during the first 5 weeks of vaccine priming elicited a higher anti-GD2 IgG1 antibody response in group 2 (1.80; 90% CI, 0.12-3.39; P = .08; planned type I error, 0.10). Anti-GD2 IgG1 titer of 230 ng/mL or greater by week 8 was associated with statistically favorable PFS. Antibody titer correlated significantly with dectin-1 SNP. The genotype frequency, seroconversion rates, and vaccine-related toxic effects were similar in the 2 groups.Conclusions and RelevanceThis phase 2 randomized clinical trial found that adding oral β-glucan during vaccine priming increased anti-GD2 IgG1 titer among genetic responders without added toxic effects. Because responder dectin-1 SNP was identical in the 2 randomized groups, no difference was detected in seroconversion rates. Alternative or additional adjuvants may be needed to enhance seroconversion.Trial RegistrationClinicalTrials.gov Identifier: NCT00911560

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Murine Anti-GD2 Monoclonal Antibody 3F8 Combined With Granulocyte-Macrophage Colony-Stimulating Factor and 13-Cis-Retinoic Acid in High-Risk Patients With Stage 4 Neuroblastoma in First Remission

Abstract: Retrospective analysis of consecutive trials from a single center demonstrated that MoAb 3F8 + GM-CSF + CRA is effective against chemotherapy-resistant marrow MRD. Its positive impact on long-term survival can only be confirmed definitively by randomized studies.

Cited by 225 publications

References 46 publications

Prolonged progression-free survival after consolidating second or later remissions of neuroblastoma with Anti-G_D2immunotherapy and isotretinoin: a prospective Phase II study

Prolonged progression-free survival after consolidating second or later remissions of neuroblastoma with Anti-G_D2immunotherapy and isotretinoin: a prospective Phase II study

Humanized 3F8 Anti-G_D2Monoclonal Antibody Dosing With Granulocyte-Macrophage Colony-Stimulating Factor in Patients With Resistant Neuroblastoma

Effect of Oral β-Glucan on Antibody Response to Ganglioside Vaccine in Patients With High-Risk Neuroblastoma

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Murine Anti-GD2 Monoclonal Antibody 3F8 Combined With Granulocyte-Macrophage Colony-Stimulating Factor and 13-Cis-Retinoic Acid in High-Risk Patients With Stage 4 Neuroblastoma in First Remission

Abstract: Retrospective analysis of consecutive trials from a single center demonstrated that MoAb 3F8 + GM-CSF + CRA is effective against chemotherapy-resistant marrow MRD. Its positive impact on long-term survival can only be confirmed definitively by randomized studies.

Cited by 225 publications

References 46 publications

Prolonged progression-free survival after consolidating second or later remissions of neuroblastoma with Anti-GD2immunotherapy and isotretinoin: a prospective Phase II study

Prolonged progression-free survival after consolidating second or later remissions of neuroblastoma with Anti-GD2immunotherapy and isotretinoin: a prospective Phase II study

Humanized 3F8 Anti-GD2Monoclonal Antibody Dosing With Granulocyte-Macrophage Colony-Stimulating Factor in Patients With Resistant Neuroblastoma

Effect of Oral β-Glucan on Antibody Response to Ganglioside Vaccine in Patients With High-Risk Neuroblastoma

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Product

Resources

About

Prolonged progression-free survival after consolidating second or later remissions of neuroblastoma with Anti-G_D2immunotherapy and isotretinoin: a prospective Phase II study

Prolonged progression-free survival after consolidating second or later remissions of neuroblastoma with Anti-G_D2immunotherapy and isotretinoin: a prospective Phase II study

Humanized 3F8 Anti-G_D2Monoclonal Antibody Dosing With Granulocyte-Macrophage Colony-Stimulating Factor in Patients With Resistant Neuroblastoma