Salvage therapy for multiple myeloma: the University of Arkansas experience

To summarize a spectrum of salvage regimens for multiple myeloma (MM) developed during the past decade.

We reviewed the experience at the University of Arkansas in the management of patients with MM who failed to achieve remission ("primary unresponsive") or had a relapse despite myelosuppressive doses of chemotherapy ("resistant relapse").

Results with use of the various chemotherapeutic protocols are presented, and multivariate regression analysis was applied to determine the independent contributions of certain factors toward event-free and overall survival.

The VAD regimen (vincristine sulfate, Adriamycin [doxorubicin hydrochloride], and dexamethasone) yielded responses in 29% of previously unresponsive and 46% of relapsed cases of MM, in comparison with 25% and 21%, respectively, with use of dexamethasone only. Responses occurred more frequently when tumor cell RNA content was high, tumor burden was low, and duration of drug resistance was less than 1 year. The duration of survival in patients who received high doses of melphalan was decreased in those with increased serum levels of lactate dehydrogenase. EDAP (etoposide, dexamethasone, ara-C, and cisplatin) produced 75% or more tumor cytoreduction in 8 of 20 patients. Overall in patients with an increasing number of adverse factors, response rates and survival decreased progressively with less intensive therapy but were unaffected when more intensive therapy was used. In the multivariate analysis, the most important features for extended survival were a low beta 2-microglobulin level before transplantation and application of two bone marrow transplants within 6 months.

Variables relative to the patient's overall medical condition, prior treatment, characteristics of MM at diagnosis, and response history should be carefully assessed to determine a plan for salvage therapy that will maximize the opportunity for sustained remission and survival.