Compartmental intrathecal radioimmunotherapy: results for treatment for metastatic CNS neuroblastoma

Abstract

Innovation in the management of brain metastases is needed. We evaluated the addition of compartmental intrathecal antibody-based radioimmunotherapy (cRIT) in patients with recurrent metastatic central nervous system (CNS) neuroblastoma following surgery, craniospinal irradiation, and chemotherapy. 21 patients treated for recurrent neuroblastoma metastatic to the CNS received a cRIT-containing salvage regimen incorporating intrathecal 131I-monoclonal antibodies (MoAbs) targeting GD2 or B7H3 following surgery and radiation. Most patients also received outpatient craniospinal irradiation, 3F8/GMCSF immunotherapy, 13-cis-retinoic acid and oral temozolomide for systemic control. Seventeen of 21 cRIT-salvage patients are alive 7-74 months (median 33) since CNS relapse, with all 17 remaining free of CNS neuroblastoma. One patient died of infection at 22 months with no evidence of disease at autopsy, and one of lung and bone marrow metastases at 15 months, and one of progressive bone marrow disease at 30 months. The cRIT-salvage regimen was well tolerated, notable for myelosuppression minimized by stem cell support (n=5), and biochemical hypothyroidism (n=5). One patient with a 7-year history of metastatic neuroblastoma is in remission from MLL-associated secondary leukemia. This is significantly improved to published results with non-cRIT based where relapsed CNS NB has a median time to death of approximately 6 months. The cRIT-salvage regimen for CNS metastases was well tolerated by young patients, despite their prior history of intensive cytotoxic therapies. It has the potential to increase survival with better than expected quality of life.

Prolonged progression-free survival after consolidating second or later remissions of neuroblastoma with Anti-GD2immunotherapy and isotretinoin: a prospective Phase II study

“…Examples include investigative agents 1 (e.g., fenretinide 37 and crizotinib 38 ), and targeted radiotherapy using 131 I-MIBG or radiolabeled mAbs. 39,40 Immunotherapy with anti-G D2 mAbs might eradicate remaining MRD, as has been documented in patients in first CR/VGPR 23 and as shown now in the current report on second or later CR/VGPR. Success against isolated CNS relapse (Tables 2 and 3), which historically heralded a rapid demise, 41 supports the curative potential of the above strategy.…”

Anti-GD2 MABS and Next-Generation mAb-Based Agents for Cancer Therapy

“…The No measurable responses; 3 pts showed evidence of antitumor activity [96] hu14.18-IL2 I Metastatic MEL (33) No measurable responses; 8 pts had SD [97] hu14.18-IL2 I/II Stage 4 MEL (9) No measurable responses; 2 pts had SD [98] hu14.18-IL2 II Metastatic MEL (14) PR in 1 pt, SD in 4 pts [99] Hu14.18-IL2 II Relapsed/refractory NBL (38) CR in 5 pts [100] Radiolabeled mAbs 131I-3F8 I GD2+ tumors metastasized to CNS and leptomeninges (15) 3 pts with objective radiographic and/or cytologic responses. 2 pts in remission for more than 3.5 yrs [160] 131I-3F8 or 131I-8H9 I Recurrent NBL metastatic to the CNS (21) 17 pts are alive 7-74 months (median 33 months) since CNS relapse, with all 17 remaining free of CNS NBL [117] CAR T cells [136] GD2-CAR T cells I Recurrent/refractory advanced-stage NBL (11) CR in 1 pt and 4 pts had evidence of tumor necrosis or regressions [161] Anti-idiotype vaccine…”

Targeted immunotherapy for pediatric solid tumors

“…There was minimal toxicity and 17 patients remained free of CNS neuroblastoma with a median of 33 mo. 16 …”