Survival in metastatic Ewing sarcoma (EWS) and rhabdomyosarcoma (RMS) following consolidation immunotherapy with autologous lymphocyte infusion, dendritic cell vaccines ± CYT107 (rhIL-7).
ABSTRACT
Background: Higher lymphocyte levels correlate with better survival in a variety of cancers, but it remains unclear whether there is a causal relationship between immune function and survival in cancer patients. A pilot study in high-risk pediatric sarcomas was undertaken to determine if a regimen designed to enhance immune reconstitution following standard cytotoxic therapy could improve survival.
Methods: Forty-four patients (median 16 yrs, range 5-33) enrolled following a diagnosis of metastatic or late recurrent pediatric sarcoma, and underwent apheresis to collect mononuclear cells and tumor biopsy to generate tumor lysate, then received standard therapy at their home institution. After standard therapy, 29 patients received immunotherapy, comprising a single infusion of autologous lymphocytes depleted of CD4+CD25+regulatory T cells, plus dendritic cell vaccines pulsed with autologous tumor lysate and keyhole limpet hemocyanin (KLH, Q14d x 6). After the first 5 patients, CYT107 (rhIL-7, 20 mcg/kg SQ Q14d x 4) was added to the regimen. Intensive biologic analyses measured global and regulatory T cell immune reconstitution and vaccine responses.
Results: This outpatient regimen was well tolerated with toxicities limited to rash, low-grade fever and mild constitutional symptoms. CYT107 dramatically enhanced global immune reconstitution and diminished regulatory T cell frequency. All patients developed immune responses to KLH and 31% developed immune responses to tumor lysate. Intent-to-treat analysis of all patients enrolled shows 56% 5-yr OS, with immunotherapy recipients having a 64% 5-yr OS (median f/u 30 mos, range 23-65). Intent-to-treat analysis of the subset of patients enrolled at the time of a new diagnosis of metastatic EWS or RMS shows 83% 5-yr OS and 54% 5-yr EFS (n=13, median f/u 35 mos, range 24-63), which is superior to previous outcomes reported for this population.
Conclusions: A low intensity immunotherapy regimen focused on enhancing immune reconstitution following standard therapy may diminish recurrence in newly diagnosed metastatic EWS and RMS. Clinical trial information: NCT00923351.