Phase 1 trial of autologous dendritic cell vaccination with imiquimod immunomodulation in children and adults with refractory sarcoma.
Authors: Dhir Aditi , Koru-Sengul Tulay , Grosso James , D'Amato Gina Z. , Trucco Matteo M. , Rosenberg Andrew , Gilboa Eli , Goldberg John M. , Trent Jonathan C. , Wilky Breelyn A. 
Published: June 2021

11542 Background: Sarcomas are rare, heterogeneous, and aggressive neoplasms that often affect otherwise healthy individuals. Patients with advanced or metastatic sarcomas have dismal outcomes. Immunotherapy presents promising new modalities to help treat sarcomas. One such therapy, autologous dendritic cell (DC) vaccines, using antigen-loaded DCs, intensify the adaptive immune response by enhancing T-cell activity and inducing tumor cell death through apoptosis and cytolysis. We present the results of a phase 1 study of DC vaccine for refractory sarcomas. Methods: A phase 1 dose-escalation study of autologous DC vaccination was conducted in children and adults with recurrent/refractory sarcomas who underwent surgical resection of a primary or metastatic tumor between 2014-2019. A 5+3 dose-escalation schema was chosen to determine safety and recommended phase 2 dose. Patient monocytes were collected by pheresis and incubated with GM-CSF plus IL-4 to generate immature DCs which were then loaded with autologous tumor lysates from the patient’s surgical resection. Three dose levels, 3, 6, and 12 million DCs per treatment were tested. The DC product was administered intradermally in imiquimod-treated skin to complete in situ maturation. Treatment consisted of four weekly injections of the DC product, followed by four monthly “boosters” of tumor lysate. The primary and secondary endpoints included safety/feasibility and preliminary clinical efficacy, respectively. Results: Nineteen patients were enrolled with a median age 50 years (13-75 years) and 47% female. Seven patients were treated on dose level 1 and six each on dose level 2 and 3. Thirteen patients received all planned injections while the remaining six patients progressed during treatment. There was no treatment related dose limiting toxicity. Grade 1-2 fever, headache, arthralgia, injection site reaction attributable to treatment were noted in four patients. There were no adverse events > grade 2. Disease progression before or after completion of study treatment was noted in 15 patients with a median PFS of 9.5 months (95%CI 5.6-28.7). The two-year PFS and OS was 36.8% and 68.1%, respectively. There were seven deaths due to disease, one patient was discharged to hospice and two patients have been lost to follow up. Five patients are currently receiving alternative therapy. Four patients remain in follow up without evidence of disease progression including three patients (pleomorphic myxofibrosarcoma, pleomorphic myosarcoma, and leiomyosarcoma) who are disease free over two years from initiating study therapy and one pediatric patient (Ewing sarcoma) disease free for over one year. Conclusions: Autologous DC vaccine with imiquimod immunomodulation for patients with relapsed/refractory sarcomas is feasible and well-tolerated. Refinement to augment initial and sustained antitumor activity is needed. Clinical trial information: NCT01803152.