Purpose: Patients with metastatic or recurrent Ewing's sarcoma family of tumors and alveolar rhabdomyosarcoma have <25% 5-year survival in most studies. This study administered a novel immunotherapy regimen aimed at consolidating remission in these patients. Experimental Design: Fifty-two patients with translocation positive, recurrent, or metastatic Ewing's sarcoma family of tumors or alveolar rhabdomyosarcoma underwent prechemotherapy cell harvest via apheresis for potential receipt of immunotherapy. Following completion of standard multimodal therapy, 30 patients ultimately initiated immunotherapy and were sequentially assigned to three cohorts. All cohorts received autologous T cells, influenza vaccinations, and dendritic cells pulsed with peptides derived from tumor-specific translocation breakpoints and E7, a peptide known to bind HLA-A2. Cohort 1 received moderate-dose recombinant human interleukin-2 (rhIL-2), cohort 2 received low-dose rhIL-2, and cohort 3 did not receive rhIL-2. Results: All immunotherapy recipients generated influenza-specific immune responses, whereas immune responses to the translocation breakpoint peptides occurred in 39%, and only 25% of HLA-A2 + patients developed E7-specific responses. Toxicity was minimal. Intention-to-treat analysis revealed a 31% 5-year overall survival for all patients apheresed (median potential follow-up 7.3 years) with a 43% 5-year overall survival for patients initiating immunotherapy. Conclusions: Consolidative immunotherapy is a scientifically based and clinically practical approach for integrating immunotherapy into a multimodal regimen for chemoresponsive cancer. Patients receiving immunotherapy experienced minimal toxicity and favorable survival.The robust influenza immune responses observed suggest that postchemotherapy immune incompetence will not fundamentally limit this approach. Future studies will seek to increase efficacy by using more immunogenic antigens and more potent dendritic cells.Impressive advances in the last 30 years for patients with clinically localized Ewing's sarcoma family of tumors (ESFT) and alveolar rhabdomyosarcoma (AR) have led to current survival rates of 60% to 70% (1 -3). However, several clinical groups continue to fare poorly, and long-term toxicity related to therapy is substantial (4). ESFT patients who present with isolated pulmonary metastases have 5-year survival rates f30%, whereas <20% of ESFT patients with bone or bone marrow involvement at initial diagnosis survive (5 -7), and ESFT patients who recur after frontline therapy also have dismal long-term survival rates (8, 9). Similarly, 5-year survival rates among patients with newly diagnosed metastatic AR are <25% (1, 10), and of the 30% to 40% of patients who present with localized disease but relapse after frontline therapy, most will eventually die of progressive disease (9, 11). Several chemotherapy regimens have shown activity in recurrent , but none of these regimens are curative. Therefore, novel therapeutic approaches are needed to improve ...
Pediatric patients tolerate 10 mg/kg of lexatumumab administered once every 14 days, the maximum-tolerated dose identified in adults. The drug seems to mediate some clinical activity in pediatric solid tumors and may work with radiation to enhance antitumor effects.
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