Progression-Free Survival and Patterns of Response in Patients With Relapsed High-Risk Neuroblastoma Treated With Irinotecan/Temozolomide/Dinutuximab/Granulocyte-Macrophage Colony-Stimulating Factor

Lerman, Benjamin J; Li, Yimei; Carlowicz, Cecilia; Granger, Meaghan; Cash, Thomas F.; Sadanand, Arhanti; Somers, Katherine; Ranavaya, Aeesha; Weiss, Brian; Choe, Michelle; Foster, Jennifer; Pinto, Navin; Morgenstern, Daniel A.; Rafael, Margarida; Streby, Keri A.; Zeno, Rachel N.; Mody, Rajen; Yazdani, Sahr; Desai, Ami; Macy, Margaret E.; Shusterman, Suzanne; Federico, Sara M.; Bagatell, Rochelle

doi:10.1200/jco.22.01273

Cited by 17 publications

(11 citation statements)

References 22 publications

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“…According to the authors, longer time from first chemotherapy to therapy with m3F8 had no impact on EFS in a multivariate analysis ( p = 0.156), so the postponed implementation of immunotherapy caused by recovery time after ASCT should not negatively influence survival [ 28 ]. The authors do not report on subsequent therapies, but comparable OS for both groups in the study may also be strongly influenced by the more effective treatment of relapses, given a time-consistent trend for increased risk of relapse without MAT+ASCT (5-year EFS: 51% versus 65%, p = 0.128) [ 67 ].…”

Section: Discussionmentioning

confidence: 99%

Survival Benefit of Myeloablative Therapy with Autologous Stem Cell Transplantation in High-Risk Neuroblastoma: A Systematic Literature Review

Żebrowska,

Balwierz,

Wechowski

et al. 2024

Targ Oncol

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Background Multimodal treatment of newly diagnosed high-risk neuroblastoma (HRNB) includes induction chemotherapy, consolidation with myeloablative therapy (MAT) and autologous stem cell transplantation (ASCT), followed by anti-disialoganglioside 2 (GD2) immunotherapy, as recommended by the Children’s Oncology Group (COG) and the Society of Paediatric Oncology European Neuroblastoma (SIOPEN). Some centres proposed an alternative approach with induction chemotherapy followed by anti-GD2 immunotherapy, without MAT+ASCT. Objective The aim of this systematic literature review was to compare survival outcomes in patients with HRNB treated with or without MAT+ASCT and with or without subsequent anti-GD2 immunotherapy. Patients and Methods The review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. MEDLINE via PubMed and EMBASE databases were systematically searched for randomised controlled trials (RCT) and observational comparative studies in patients with HRNB using search terms for ‘neuroblastoma’ and (‘myeloablative therapy’ OR ‘stem cell transplantation’). Reporting of at least one survival outcome [event-free survival (EFS), progression-free survival, relapse-free survival and/or overall survival (OS)] was required for inclusion. Outcomes from RCTs were synthesized in meta-analysis, while meta-analysis of non-RCTs was not planned owing to expected heterogeneity. Results Literature searches produced 2587 results with 41 publications reporting 34 comparative studies included in the review. Of these, 7 publications reported 4 RCTs, and 34 publications reported 30 non-RCT studies. Studies differed with respect to included populations, induction regimen, response to induction, additional treatments and transplantation procedures. Subsequent treatments of relapse were rarely reported and could not be compared. In the meta-analysis, EFS was in favour of MAT+ASCT over conventional chemotherapy or no further treatment [hazard ratio (HR) = 0.78, 95% confidence interval (CI) 0.67−0.91, p = 0.001] with a trend favouring MAT+ASCT for OS (HR = 0.86, 95% CI 0.73−1.00, p = 0.05). Tandem MAT+ASCT was found to improve EFS compared with the single procedure, with improvement in both EFS and OS in patients treated with anti-GD2 therapy. Non-RCT comparative studies were broadly consistent with evidence from the RCTs; however, not all reported survival benefits of MAT+ASCT (single or tandem). Limited comparative evidence on treatment without MAT+ASCT in patients treated with anti-GD2 immunotherapy suggests an increased risk of relapse. In relapsed patients, MAT+ASCT appears to improve OS, but evidence remains scarce. Conclusions Survival benefits in patients treated with MAT+ASCT confirm that the procedure should remain an integral part of multimodal therapy. In patients treated with anti-GD2 immunot...

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Section: Discussionmentioning

confidence: 99%

Survival Benefit of Myeloablative Therapy with Autologous Stem Cell Transplantation in High-Risk Neuroblastoma: A Systematic Literature Review

Żebrowska,

Balwierz,

Wechowski

et al. 2024

Targ Oncol

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“…Data from the non-randomized extension of the registration trial demonstrated lower grade 3-4 hematologic adverse events in sargramostim cycles vs IL-2 cycles. 27 Other studies demonstrated the benefit of adding dinutuximab plus sargramostim to chemotherapy for relapsed/ refractory HR-NB, 82,84,85 including patients previously treated with anti-GD2 therapy. 84,85 A more recent study explored earlier use of dinutuximab with GM-CSF as part of induction therapy in HR-NB and showed promising end-of-induction objective response rates of up to 87%.…”

Section: Clinical Datamentioning

confidence: 99%

“…27 Other studies demonstrated the benefit of adding dinutuximab plus sargramostim to chemotherapy for relapsed/ refractory HR-NB, 82,84,85 including patients previously treated with anti-GD2 therapy. 84,85 A more recent study explored earlier use of dinutuximab with GM-CSF as part of induction therapy in HR-NB and showed promising end-of-induction objective response rates of up to 87%. 87 Additional dinutuximab studies are summarized in Table S2.…”

Section: Clinical Datamentioning

confidence: 99%

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GM‐CSF, G‐CSF or no cytokine therapy with anti‐GD2 immunotherapy for high‐risk neuroblastoma

Mora,

Modak,

Kinsey

et al. 2023

Intl Journal of Cancer

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Colony‐stimulating factors have been shown to improve anti‐disialoganglioside 2 (anti‐GD2) monoclonal antibody response in high‐risk neuroblastoma by enhancing antibody‐dependent cell‐mediated cytotoxicity (ADCC). A substantial amount of research has focused on recombinant human granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) as an adjuvant to anti‐GD2 monoclonal antibodies. There may be a disparity in care among patients as access to GM‐CSF therapy and anti‐GD2 monoclonal antibodies is not uniform. Only select countries have approved these agents for use, and even with regulatory approvals, access to these agents can be complex and cost prohibitive. This comprehensive review summarizes clinical data regarding efficacy and safety of GM‐CSF, recombinant human granulocyte colony‐stimulating factor (G‐CSF) or no cytokine in combination with anti‐GD2 monoclonal antibodies (ie, dinutuximab, dinutuximab beta or naxitamab) for immunotherapy of patients with high‐risk neuroblastoma. A substantial body of clinical data support the immunotherapy combination of anti‐GD2 monoclonal antibodies and GM‐CSF. In contrast, clinical data supporting the use of G‐CSF are limited. No formal comparison between GM‐CSF, G‐CSF and no cytokine has been identified. The treatment of high‐risk neuroblastoma with anti‐GD2 therapy plus GM‐CSF is well established. Suboptimal efficacy outcomes with G‐CSF raise concerns about its suitability as an alternative to GM‐CSF as an adjuvant in immunotherapy for patients with high‐risk neuroblastoma. While programs exist to facilitate obtaining GM‐CSF and anti‐GD2 monoclonal antibodies in regions where they are not commercially available, continued work is needed to ensure equitable therapeutic options are available globally.

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“…1 Data from Children's Oncology Group modern era early-phase trials suggests that only one in five children with recurrent/refractory neuroblastoma will survive 4 years from time of trial enrollment. 2 Despite recent advances in combination chemotherapy and immunotherapy, 3 children with recurrent/refractory neuroblastoma often experience a high burden of distressing symptoms, and prior work has identified receipt of moderate or highintensity cancer-directed therapy as a contributor to suffering. 4 Parents often hold onto curative hopes and goals for their children with cancer in the face of progressing disease.…”

Section: Introductionmentioning

confidence: 99%

Factors influencing parents’ choice of palliative treatment goals for children with relapsed or refractory neuroblastoma: A multi‐site longitudinal survey study

Kaye,

Smith,

Zhou

et al. 2023

Cancer

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BackgroundMany parents of children with advanced cancer report curative goals and continue intensive therapies that can compound symptoms and suffering. Factors that influence parents to choose palliation as the primary treatment goal are not well understood. The objective of this study was to examine experiences impacting parents’ report of palliative goals adjusted for time. The authors hypothesized that awareness of poor prognosis, recall of oncologists’ prognostic disclosure, intensive treatments, and burdensome symptoms and suffering would influence palliative goal‐setting.MethodsThe authors collected prospective, longitudinal surveys from parents of children with relapsed/refractory neuroblastoma at nine pediatric cancer centers across the United States, beginning at relapse and continuing every 3 months for 18 months or until death. Hypothesized covariates were examined for possible associations with parental report of palliative goals. Generalized linear mixed models were used to evaluate factors associated with parents’ report of palliative goals at different time points.ResultsA total of 96 parents completed surveys. Parents were more likely to report a primary goal of palliation when they recalled communication about prognosis by their child’s oncologist (odds ratio [OR], 52.48; p = .010). Treatment intensity and previous ineffective therapeutic regimens were not associated with parents’ report of palliative goals adjusted for time. A parent who reported new suffering for their child was less likely to report palliative goals (OR, 0.13; p = .008).ConclusionsParents of children with poor prognosis cancer may not report palliative goals spontaneously in the setting of treatment‐related suffering. Prognostic communication, however, does influence palliative goal‐setting. Evidence‐based interventions are needed to encourage timely, person‐centered prognostic disclosure in the setting of advanced pediatric cancer.Plain Language Summary Many parents of children with poor‐prognosis cancer continue to pursue curative treatments that may worsen symptoms and suffering. Little is known about which factors influence parents to choose palliative care as their child’s main treatment goal. To explore this question, we asked parents of children with advanced neuroblastoma across the United States to complete multiple surveys over time. We found that the intensity of treatment, number of treatments, and suffering from treatment did not influence parents to choose palliative goals. However, when parents remembered their child’s oncologist talking about prognosis, they were more likely to choose palliative goals of care.

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Progression-Free Survival and Patterns of Response in Patients With Relapsed High-Risk Neuroblastoma Treated With Irinotecan/Temozolomide/Dinutuximab/Granulocyte-Macrophage Colony-Stimulating Factor

Cited by 17 publications

References 22 publications

Survival Benefit of Myeloablative Therapy with Autologous Stem Cell Transplantation in High-Risk Neuroblastoma: A Systematic Literature Review

Survival Benefit of Myeloablative Therapy with Autologous Stem Cell Transplantation in High-Risk Neuroblastoma: A Systematic Literature Review

GM‐CSF, G‐CSF or no cytokine therapy with anti‐GD2 immunotherapy for high‐risk neuroblastoma

Factors influencing parents’ choice of palliative treatment goals for children with relapsed or refractory neuroblastoma: A multi‐site longitudinal survey study

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