Treatment with vorinostat and 131iodine-metaiodobenzylguanidine (MIBG) proved more effective than MIBG alone or in combination with vincristine and irinotecan in children and young adults with relapsed or refractory neuroblastoma, according to a phase 2 study published in the Journal of Clinical Oncology.

The phase 2 trial ( Identifier: NCT02035137) included 105 patients with relapsed or refractory neuroblastoma. The patients’ median age was 6.5 years (range, 1.8-28.1 years), and 55 were male.

Patients were randomly assigned to receive MIBG alone (n=36), MIBG plus vincristine and irinotecan (n=35), or MIBG plus vorinostat (n=34).

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After 1 course of treatment, the overall response rate (ORR) was 14% with MIBG alone, 14% with MIBG-vincristine-irinotecan, and 32% with MIBG-vorinostat.

The response rates at soft tissue sites were 7% with MIBG alone, 15% with MIBG-vincristine-irinotecan, and 16% with MIBG-vorinostat. Response rates in the bone marrow were 5%, 18%, and 14%, respectively.

Some patients received a second course of therapy — 6 in the MIBG-alone arm, 11 in the MIBG-vincristine-irinotecan arm, and 10 in the MIBG-vorinostat arm.

The best ORR to the first or second course was 14% in the MIBG-alone arm, 17% in the MIBG-vincristine-irinotecan arm, and 35% in the MIBG-vorinostat arm.   

Among the 27 patients who received 2 courses of therapy, the best ORR was 17% for MIBG alone, 36% for MIBG-vincristine-irinotecan, and 60% for MIBG-vorinostat.

Grade 3-4 adverse events (AEs) were most common in patients who received MIBG-vincristine-irinotecan. There were no grade 5 AEs in any treatment arm.

After the first treatment course, rates of grade 3-4 nonhematologic AEs were 49% in the MIBG-vincristine-irinotecan arm, 35% in the MIBG-vorinostat arm, and 19% in the MIBG-alone arm.

The most common grade 3-4 AEs in the MIBG-alone arm were blood and lymphatic system disorders (6%). The most common grade 3-4 AEs in the MIBG-vorinostat arm were hypokalemia (9%) and vomiting (6%).

The most common grade 3-4 AEs in the MIBG-vincristine-irinotecan arm were vomiting (17%), anorexia (14%), diarrhea (11%), dehydration (11%), and febrile neutropenia (9%).

One patient in the MIBG-vincristine-irinotecan arm and 2 in the MIBG-vorinostat arm developed myelodysplastic syndrome or acute myeloid leukemia.

“The combination of MIBG plus vorinostat provides a new option for patients with relapsed or refractory neuroblastoma,” the study authors wrote. “Future studies may build upon these findings to investigate the role of epigenetic modifiers as potential radiation sensitizers in this disease and in other cancers.”

Disclosures: This research was partly supported by Merck. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


DuBois SG, Granger MM, Groshen S, et al. Randomized phase II trial of MIBG versus MIBG, vincristine, and irinotecan versus MIBG and vorinostat for patients with relapsed or refractory neuroblastoma: A report from NANT consortium. J Clin Oncol. Published July 16, 2021. doi:10.1200/JCO.21.00703