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."