Maria Antonietta De Ioris, Francesca Del Bufalo, Concetta Quintarelli, Valentina Bertaina, Francesco Fabozzi, Maria Giuseppina Cefalo, Iside Alessi, Chiara Grimaldi, Maria Felicia Villani, Maria Luisa D'Andrea, Alessandra Stracuzzi, Claudio Altini, Carmen Malaspina, Matilde Sinibaldi, Stefano Di Cecca, Laura Iaffaldano, Clelia Geraci, Marco Becilli, Biagio De Angelis, Alessandro Crocoli, Giulia Cassanelli, Stefano Margaritora, Angela Mastronuzzi, Franco Locatelli
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.
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.