After the discovery of melphalan and prednisone (MP), many clinical trials evaluated the
efficacy of combination chemotherapy, such as VMCP, VBAP, MOCCA in multiple myeloma (MM)
patients, without significant clinical benefit. After 40 years, the combination of MP with
thalidomide (MPT) or lenalidomide (MPR) or bortezomib (MPV) have finally and consistently
shown additive or synergistic effects.In advanced MM, the combination of melphalan,
prednisone and thalidomide induced 12% very good partial response (VGPR) rate, while the
combination of melphalan and bortezomib showed 15% near complete remission (nCR) rate. In
relapsed patients, the combination of bortezomib with MPT (VMPT) induced 43% VGPR rate.
Preliminary results indicate that VMPT may induce a CR rate of around 50% in newly diagnosed
patients (unpublished results).In preclinical studies thalidomide showed more
anti-angiogenesis activity, while lenalidomide showed more immunomodulatory effects, thus
suggesting a combined clinical approach for these two drugs. The toxicity profile of
lenalidomide is completely different from that of thalidomide and no cumulative toxicities
are expected, again suggesting a combination approach. This study will evaluate the safety
and efficacy of combining Lenalidomide, Melphalan, Prednisone and Thalidomide (R-MPT) as
salvage treatment for relapsed/refractory myeloma patients. This association might further
increase the response rate achieved by the standard oral MPT or MPR regimens.