LITTLE ROCKHigh-dose chemotherapy with bone-marrow transplant
produces complete remissions in about 40% of multiple myeloma
patients, but current maintenance therapy is not able to maintain
this response. New preliminary data, however, show that multiple
myeloma patients who receive a purified immunoglobulin idiotype
protein as a vaccine after high-dose chemotherapy and transplant are
likely to have improved event-free survival. Nikhil C. Munshi, MD, of
the University of Arkansas for Medical Sciences reported these
preliminary results at the ASH meeting.
A purified Ig protein (0.5 mg) conjugated to keyhole limpet
hemocyanian (KLH) as a carrier was used to construct the vaccine. The
resulting Id-KLH vaccine was subcutaneously administered together
with GM-CSF at the injection site to seven patients who had complete
responses and 11 patients who had partial responses following
Patients were first vaccinated 3 months after chemotherapy and
transplant, when each patient had complete hematopoietic recovery.
Each of the first cohort of 18 patients received 3 vaccinations.
All Responded to KLH
Dr. Munshi described clinical results from the first 7 patients
treated and immunological responses from all 18 patients. None had
pre-vaccination responses to idiotype. After vaccination, 15 of 18
patients had anti-Id-KLH antibody responses; 10 had cytokine
responses to idiotype challenge; 13 had cell proliferation responses;
and 6 had developed cutaneous hypersensitivity to idiotype. All
of those treated responded to KLH, suggesting that their immune
systems were intact, Dr. Munshi said.
Median follow-up was 27 months in the 7 patients evaluable for
response. Two had partial responses which became complete responses,
but since they were vaccinated within 6 months of receiving high-dose
chemotherapy, Dr. Munshi said that it was not possible to determine
whether this effect was due to the vaccination or to the
chemotherapy. Five of the 7 patients are in sustained complete
Further Follow-up Needed
Dr. Munshi said that event-free survival was superior in patients who
developed idiotype-specific T-cell responses and that the
investigators are now trying to determine why some patients develop
T-cell responses but others do not.
Multiple myeloma patients are immune competent following
autologous transplant. Most can produce an anti-idiotype T-cell
response, and a T-cell proliferative response may suggest superior
survival, Dr. Munshi concluded. Idiotype vaccination
provides significant immunological responses following
transplantation, but the clinical benefit requires longer follow-up
to evaluate effects on event-free and overall survival.