Idiotype Protein Vaccine Improves Survival in Post-Transplant Multiple Myeloma

LITTLE ROCK—High-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 high-dose chemotherapy.

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 response.

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.”