Dinutuximab beta with TEMIRI chemotherapy in relapsed/refractory neuroblastoma: Real-world insights into the open question of GD2 expression.
In a 25-child real-world series of relapsed/refractory neuroblastoma, short-schedule dinutuximab beta plus temozolomide–irinotecan produced a 52% best overall response rate, with stronger bone and bone-marrow responses and heterogeneous, treatment-associated changes in tumor GD2 expression.
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In a 25-child real-world series of relapsed/refractory neuroblastoma, short-schedule dinutuximab beta plus temozolomide–irinotecan produced a 52% best overall response rate, with stronger bone and bone-marrow responses and heterogeneous, treatment-associated changes in tumor GD2 expression.
Research significance
The reported responses support further prospective study of dinutuximab beta plus TEMIRI in relapsed/refractory neuroblastoma; it is an inference—not established by this uncontrolled series—that serial GD2 assessment could help select patients, explain site-specific response, or guide subsequent GD2-directed therapy.
Source abstract
INTRODUCTION: Prognosis of Relapsed/Refractory (R/R) neuroblastoma is still dismal. Chemoimmunotherapy has been reported to improve the response rate. PATIENTS AND METHODS: Dinutuximab beta added to chemotherapy was used in an off-label setting. Treatment was administered on a 21-day schedule: on day 1 Irinotecan was administered at the dose of 50 mg/m2/day for 5 days, together with Temozolomide, at the dose of 100 mg/m2/day for 5 days. Dinutuximab beta was administered from day 2 at the dose of 17,5 mg/m2/day for 4 consecutive days. RESULTS: Twenty-five children received chemo-immunotherapy. Hematological toxicity was the most common adverse event. The best overall response rate (ORR) was 52% (95% CI:31-72), with an ORR of 62% (95% CI: 38-82) at metastatic sites. Responses were higher at bone and bone marrow sites (ORR 67% and 92%, respectively). SIOPEN skeletal score declined during treatment, the best response being observed after the first 2/3 courses. Primary tumors and soft-tissue lesions were less responsive, though metabolic activity often decreased. Negative or low GD2 expression was observed in 10% and in 35% of tumor tissue, respectively at baseline and after treatment, with mean GD2-positive tumor cells decreasing from 88% to 62% in tumor tissue, mainly associated with differentiating histology. DISCUSSION: This real-world experience confirms that a short schedule is a feasible and effective option in R/R neuroblastoma. The dynamic and heterogeneous expression of GD2 deserves further evaluation, particularly in relation to selection of patients and subsequent GD2-directed treatment strategies.