Abstract LB-201: Durable remission of lethal canine hemangiosarcoma
Authors: Halpert Matthew M. , Konduri Vanaja , Chen Yunyu , Liang Dan , Levitt Jonathan M. , Neal Brittany , Hudson Caleb , Hottinger Heidi , Piscoya Sindy , Wilson Nicola , DiBernardi Lisa , Stallings Shonda , Omarbekov Zharkyn , Seelhof Lori , Ramirez Oscar , Yao Qizhi C. , Bhardwaj Ratan D. , Ravi Vinod , Douglass Laurel , Decker William K. 
Published: July 2017

Background: Angiosarcoma is an uncommon but deadly malignant neoplasm of the vascular endothelium. Primary disease may present at any vascularized site but often occurs in the dermis on the neck and scalp or in the radiation field of women previously-treated for breast cancer. Metastases are often present at first diagnosis, and five-year survival is an abysmal 10-30%. In contrast to the relative paucity of human diagnoses, angiosarcoma is a major killer in the companion canine population, responsible for an estimated 120,000 deaths per year in the United States. The canine disease (termed HSA) closely mimics the human disease in both pathology and genetics. It frequently presents in the dog as acute hemoabdomen secondary to splenic rupture. Even if life-saving splenectomy is performed, median OS is a scant 48 days, and one-year OS hovers at 0%. Given the lack of an analogous rodent model and the accelerated timeline of the canine disease, the outbred companion canine is an ideal system in which to translate novel therapeutic approaches. Here we report an interim analysis of a phase I multi-site, open-label veterinary trial of chemo-immunotherapy performed on consecutively-presenting splenectomized companion canines with histopathologically-verified HSA.

Methods: In addition to two cycles of 20 mg/m2 (low-dose) doxorubicin, enrolled study subjects received an autologous cell-therapy reported to generate durable CD8+ memory similar to that of physiologic viral infection. Vaccine was generated from mobilized peripheral blood and cryopreserved tumor antigen and was administered in four doses given in conjunction with type I interferon. Disease burden was monitored monthly by abdominal ultrasound, chest x-ray, and echocardiogram.

Results: At the time of abstract submission, median OS had not yet been reached in the per protocol population, with 75% of animals alive and healthy (NED or ongoing PR) at up to one year post-splenectomy (p&lt;0.0002). Abdominal ultrasound documented the resolution of local mesenteric disease in one animal, sternal lymphadenopathy in another, and hepatic metastases in a third. In the intent-to-treat population, median OS was 109 days with 43% of animals alive and healthy at up to one year post-splenectomy. A single incidence of grade 1/2 uveitis resolved promptly with administration of ophthalmic corticosteroids.

Conclusions: Administration of autologous cell therapy in conjunction with low-dose doxorubicin is feasible, safe, and highly efficacious in the companion canine population. Generally, if subjects survived long enough to begin treatment, the prognosis became quite favorable. The results suggest that additional clinical studies in both canines and humans are warranted.

Citation Format: Matthew M. Halpert, Vanaja Konduri, Yunyu Chen, Dan Liang, Jonathan M. Levitt, Brittany Neal, Caleb Hudson, Heidi Hottinger, Sindy Piscoya, Nicola Wilson, Lisa DiBernardi, Shonda Stallings, Zharkyn Omarbekov, Lori Seelhof, Oscar Ramirez, Qizhi C. Yao, Ratan D. Bhardwaj, Vinod Ravi, Laurel Douglass, William K. Decker. Durable remission of lethal canine hemangiosarcoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr LB-201. doi:10.1158/1538-7445.AM2017-LB-201