VENICE, ItalyAdjuvant therapy with the investigational vaccine Melacine helps prevent relapses in patients with stage IIA melanoma, investigators from the Southwest Oncology Group (SWOG) 9035 Study Group announced at the Fifth World Conference on Melanoma. Mela-cine, being developed by Corixa (Seattle), consists of a mixture of allogeneic melanoma cell lysates plus an immunologic adjuvant (Detox).
The findings are from a phase III trial involving 689 patients with intermediate-thickness (1.5 to 4.0 mm or Clark’s level IV if tumor thickness is unknown), node-negative melanoma. After surgical excision of the primary tumor, patients were randomized to 2 years of therapy with Melacine or a strategy of "watchful waiting," per standard practice.
Subjects were stratified by criteria that included sex, tumor thickness, and regional lymph node staging. The vaccine group received a total of 40 doses of the vaccine over 2 years.
After a median follow-up of 4.1 years, 95 events (recurrences or deaths without prior recurrences) occurred among the 300 eligible patients randomized to the vaccine, compared with 106 events among the 300 patients in the "watchful waiting" group, said Vernon K. Sondak, MD, associate professor of surgery, University of Michigan Medical Center, Ann Arbor, and chair of SWOG’s melanoma committee.
The difference between the two groups was not statistically significant. However, when the entire randomized population of 689 patients was included in the evaluation, there were 103 events in the 346 patients randomized to the vaccine vs 125 events among 343 patients in the "watchful waiting" group, and the difference between the two groups was statistically significant.
Overall, the findings correlate with a 14% to 24% lower rate of disease recurrence in patients treated with the vaccine, Dr. Sondak said.
HLA Tissue Type a Factor
Results also showed that patients’ HLA tissue type was a significant factor in determining response to the vaccine. Patients who were positive for HLA-A2 and/or HLA-C3 did best after vaccination. "HLA-A2-positive or HLA-C3-positive patients represent nearly two thirds of all melanoma patients, and these may be the patients we eventually want to target for therapy with this vaccine," Dr. Sondak said.
The finding of an improved outcome in patients with certain tissue types serves as indirect evidence that the vaccine effect is mediated by specific antigens. A T-cell immune response to peptide antigens is HLA restricted, he added. A number of HLA-A2-restricted melanoma antigens are known to exist, and many are present in Melacine. Less is known about HLA-C3, but at least one C3-restricted antigen is in the Melacine vaccine.
The vaccine was well tolerated. Overall, 26 (9%) of 294 evaluable patients developed grade 3 toxicity, 187 (64%) had grade 2 toxicity, and 68 (23%) had grade 1 toxicity. Toxicities were mostly local, including granulomas and sterile abscesses at the injection sites.
"Currently, there are few treatment options once a melanoma has metastasized from a stage II lesion to a stage III lesion and beyond, and that’s why it is extremely important to halt the disease before it progresses or at least postpone its progression," Dr. Sondak commented. "Our results suggest that this tumor vaccine may help prevent relapses in stage IIA patients, particularly those with certain tissue types. Further evaluation is certainly warranted."