Dinutuximab beta plus conventional chemotherapy for relapsed/refractory high-risk neuroblastoma: A single-center experience

Olgun, Nur; Çeçen, Emre; İnce, Dilek; Kızmazoğlu, Deniz; Baysal, Birsen; Onal, Ayse; Özdoğan, Özhan; Güleryüz, Handan; Çetingöz, Rıza; Demiral, Ayşe; Olguner, Mustafa; Çelik, Ahmet; Kamer, Serra; Özer, Erdener; Altun, Zekiye; Aktaş, Safiye

doi:10.3389/fonc.2022.1041443

Cited by 10 publications

(7 citation statements)

References 36 publications

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“…This new anti-GD2 monoclonal antibody has been widely used for children with high-risk NB, as it can enhance survival. 6,26,27 However, the drug is costly, thus increasing the medical burden and financial burden on the families. Therefore, cost-effectiveness of dinutuximab β in NB children should be evaluated.…”

Section: Discussionmentioning

confidence: 99%

“…4 Nowadays, the immune-targeting drug dinutuximab β has been gradually used to improve the survival rate of children with high-risk NB. [6][7][8] Dinutuximab β acts as an antitumor agent by specifically binding to disialoganglioside (GD2) antigens highly expressed on the membrane surface of NB cells, triggering a dual immune mechanism. 3,9 A series of trials conducted by the International Society of Pediatric Oncology Europe Neuroblastoma Group have assessed the effectiveness and safety of dinutuximab β in children with high-risk NB.…”

Section: Introductionmentioning

confidence: 99%

“…In the not‐too‐distant past, the postconsolidation phase used isotretinoin to treat potential minimal residual disease 4 . Nowadays, the immune‐targeting drug dinutuximab β has been gradually used to improve the survival rate of children with high‐risk NB 6–8 . Dinutuximab β acts as an antitumor agent by specifically binding to disialoganglioside (GD2) antigens highly expressed on the membrane surface of NB cells, triggering a dual immune mechanism 3,9 .…”

Section: Introductionmentioning

confidence: 99%

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Cost‐effectiveness analysis of dinutuximab β for the treatment of high‐risk neuroblastoma in China

Shen,

Zhao,

et al. 2023

Pediatric Blood & Cancer

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BackgroundDinutuximab β can be used to treat children with high‐risk neuroblastoma (NB). Due to its high price, whether dinutuximab β is cost‐effective for the treatment of high‐risk NB remains uncertain. Therefore, assessing the cost‐effectiveness of dinutuximab β in children with high‐risk NB is of high importance.MethodsThe health utilities and economic outcomes in children with high‐risk NB were projected using a partitioned survival model. The individual patient data (IPD) of add‐on treatment with dinutuximab β (GD2 group) were derived from the literature, while the IPD of traditional therapy (TT group) were obtained from retrospective data of Shanghai Children's Medical Center. Treatment costs included drugs, adverse event‐related expenses, and medical resource use. Utility values were obtained from the literature. Costs and quality‐adjusted life‐years (QALYs) were measured over a 10‐year time horizon. Deterministic sensitivity analyses (DSA) and probabilistic sensitivity analyses (PSA) were also conducted.ResultsCompared with the TT group, QALY increased in the GD2 group by 0.72 with an increased cost of $171,269.70, leading to an incremental cost‐effectiveness ratio of 236,462.75$/QALY. DSA showed that the price of dinutuximab β was the main factor on the results than other parameters. Compared with the TT group, the GD2 group could not be cost‐effective in the PSA at the $37,920/QALY threshold.ConclusionResults found that dinutuximab β is not a cost‐effective treatment option for children with high‐risk NB unless its price is significantly reduced.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Cost‐effectiveness analysis of dinutuximab β for the treatment of high‐risk neuroblastoma in China

Shen,

Zhao,

et al. 2023

Pediatric Blood & Cancer

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“…Most recently, anti-GD2 monoclonal antibodies (mAbs) have been formally tested in the setting of primary refractory disease, and the results show the efficacy of the combination of dinutuximab with irinotecan and temozolomide (DIT) [17,18] and naxitamab for patients with primary refractory disease in the bone/bone marrow compartment [19]. The early results from using dinutuximab beta with chemotherapy also show objective responses for primary refractory neuroblastoma [20,21].…”

Section: Introductionmentioning

confidence: 99%

Early Salvage Chemo-Immunotherapy with Irinotecan, Temozolomide and Naxitamab Plus GM-CSF (HITS) for Patients with Primary Refractory High-Risk Neuroblastoma Provide the Best Chance for Long-Term Outcomes

Muñoz,

Larrosa,

Chamorro

et al. 2023

Cancers

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Patients with high-risk neuroblastoma (HR-NB) who are unable to achieve a complete response (CR) to induction therapy have worse outcomes. We investigated the combination of humanized anti-GD2 mAb naxitamab (Hu3F8), irinotecan (I), temozolomide (T), and sargramostim (GM-CSF)—HITS—against primary resistant HR-NB. Eligibility criteria included having a measurable chemo-resistant disease at the end of induction (EOI) treatment. Patients were excluded if they had progressive disease (PD) during induction. Prior anti-GD2 mAb and/or I/T therapy was permitted. Each cycle, administered four weeks apart, comprised Irinotecan 50 mg/m2/day intravenously (IV) plus Temozolomide 150 mg/m2/day orally (days 1–5); naxitamab 2.25 mg/kg/day IV on days 2, 4, 8 and 10, (total 9 mg/kg or 270 mg/m2 per cycle), and GM-CSF 250 mg/m2/day subcutaneously was used (days 6–10). Toxicity was measured using CTCAE v4.0 and responses through the modified International Neuroblastoma Response Criteria (INRC). Thirty-four patients (median age at treatment initiation, 4.9 years) received 164 (median 4; 1–12) HITS cycles. Toxicities included myelosuppression and diarrhea, which was expected with I/T, and pain and hypertension, expected with naxitamab. Grade ≥3-related toxicities occurred in 29 (85%) of the 34 patients; treatment was outpatient. The best responses were CR = 29% (n = 10); PR = 3% (n = 1); SD = 53% (n = 18); PD = 5% (n = 5). For cohort 1 (early treatment), the best responses were CR = 47% (n = 8) and SD = 53% (n = 9). In cohort 2 (late treatment), the best responses were CR = 12% (n = 2); PR = 6% (n = 1); SD = 53% (n = 9); and PD = 29% (n = 5). Cohort 1 had a 3-year OS of 84.8% and EFS 54.4%, which are statistically significant improvements (EFS p = 0.0041 and OS p = 0.0037) compared to cohort 2. In conclusion, naxitamab-based chemo-immunotherapy is effective against primary chemo-resistant HR-NB, increasing long-term outcomes when administered early during the course of treatment.

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“…However, overall survival (OS) did not differ between patients treated with chemotherapy alone and those receiving chemotherapy plus dinutuximab beta (HR 0.99, 95% CI 0.42–2.36; p = 0.99). The use of dinutuximab beta in combination with irinotecan and temozolomide in routine clinical practice was also associated with promising objective response rates of 63–64% [ 10 , 11 ]. Based on the positive findings in the relapsed/refractory setting, this chemoimmunotherapy concept was also explored in newly-diagnosed patients with high-risk NB.…”

Section: Introductionmentioning

confidence: 99%

Effect and Tolerance of N5 and N6 Chemotherapy Cycles in Combination with Dinutuximab Beta in Relapsed High-Risk Neuroblastoma Patients Who Failed at Least One Second-Line Therapy

Lode,

Ladenstein,

Troschke-Meurer

et al. 2023

Cancers

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The anti-disialoganglioside (GD2) monoclonal antibody dinutuximab beta is approved for the maintenance treatment of high-risk neuroblastoma. Dinutuximab beta combined with different chemotherapy regimens is being investigated in various clinical settings. We conducted a retrospective clinical chart review of 25 patients with relapsed/refractory neuroblastoma who had failed ≥1 second-line therapy and received compassionate use treatment with dinutuximab beta long-term infusion combined with the induction chemotherapy regimens N5 (cisplatin, etoposide, vindesine) and N6 (vincristine, dacarbazine, ifosfamide, doxorubicin) recommended by the German Pediatric Oncology and Hematology Group [GPOH] guidelines. The treatment did not result in any unexpected severe toxicities or in any major treatment delays. Grade 3/4 pain was reported by 4/25 patients in cycle 1, decreasing to 0/9 patients in cycles 3 and 4. The median follow-up was 0.6 years. The best response in this group was 48% (12/25 patients), which included three patients with minor responses. At 1 year, the estimated event-free survival was 27% (95% confidence interval [CI] 8–47) and overall survival was 44% (95% CI 24–65). Combining long-term infusion of dinutuximab beta with N5 and N6 chemotherapy demonstrated an acceptable safety profile and encouraging objective response rates in heavily pretreated patients with high-risk neuroblastoma, warranting further evaluation in clinical trials.

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Dinutuximab beta plus conventional chemotherapy for relapsed/refractory high-risk neuroblastoma: A single-center experience

Cited by 10 publications

References 36 publications

Cost‐effectiveness analysis of dinutuximab β for the treatment of high‐risk neuroblastoma in China

Cost‐effectiveness analysis of dinutuximab β for the treatment of high‐risk neuroblastoma in China

Early Salvage Chemo-Immunotherapy with Irinotecan, Temozolomide and Naxitamab Plus GM-CSF (HITS) for Patients with Primary Refractory High-Risk Neuroblastoma Provide the Best Chance for Long-Term Outcomes

Effect and Tolerance of N5 and N6 Chemotherapy Cycles in Combination with Dinutuximab Beta in Relapsed High-Risk Neuroblastoma Patients Who Failed at Least One Second-Line Therapy

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