HLA Phenotype May Determine Efficacy of New Melanoma Vaccine

SEATTLE—Melanoma patients with specific human leukocyte antigen (HLA) phenotypes may respond better to an investigational therapeutic vaccine known as Melacine than those without the phenotype, Vernon Sondak, MD, reported for the Southwest Oncology Group (SWOG) at the Society of Biological Therapy annual meeting.

Melacine, under development by Corixa Corporation (Seattle), consists of lysed cells from two human melanoma cell lines combined with Corixa’s proprietary Detox adjuvant. Detox adjuvant includes monophosphoryl lipid A and mycobacterial cell wall skeleton, both of which activate the human immune system in the context of vaccination.

Dr. Sondak previously reported results of the phase III trial of 689 stage II melanoma patients randomized to adjuvant immunotherapy with Melacine or observation following surgical excision of their primary tumor.

Although analysis of the eligible population (600 patients) showed no significant difference in disease-free survival between the two groups, intent-to-treat analysis showed significantly longer disease-free survival for patients treated with Melacine (P = .04). The vaccine was particularly beneficial in patients with thinner tumors (less than 3 mm), he said.

Expression of five HLA genes (HLA-A2, A28, B44, B45, and C3) was determined in 80% of the 689 study patients, he said. The new analysis found that disease-free survival was significantly better in vaccinated patients who expressed two or more of the five prospectively defined HLA alleles (P = .0001), compared with patients with the same HLA phenotype who were not vaccinated after surgery.

The effect was predominantly related to expression of HLA-A2, which was found in 46% of the study population, and HLA-C3 (29%). The investigators speculate that certain HLA alleles may be critical to the binding and presentation of melanoma antigens in the vaccine.