Effect of induction therapy with lenalidomide, doxorubicin, and dexamethasone on bone remodeling and angiogenesis in newly diagnosed multiple myeloma

There is limited data regarding the efficacy and safety of lenalidomide, adriamycin and dexamethasone (RAD) combination on newly diagnosed multiple myeloma (NDMM) patients. There is also scarce information about the effect of lenalidomide on bone metabolism and angiogenesis in NDMM. Thus, we conducted a phase 2 study to evaluate the efficacy and safety of RAD regimen as induction in transplant‐eligible NDMM patients and we studied the effects on bone metabolism and angiogenesis. A total of 45 patients was enrolled. Following four cycles of RAD, the overall response rate was 66.7% and after a median follow‐up of 29.1 months (range 21.0 – 34.9) the median survival outcomes have not been reached yet. RAD had a favorable toxicity profile and did not impair stem cell collection. RAD significantly reduced bone resorption markers CTX (p=0.03) and TRACP‐5b (p<0.01). Interestingly, RAD also increased bone formation markers bALP (p=0.036), P1NP (p=0.028) and OC (p=0.026), which has not been described before with lenalidomide‐containing regimens in the absence of bortezomib co‐administration. Furthermore, the angiogenic cytokines VEGF (p=0.01), angiogenin (p=0.02) and bFGF (p<0.01) were significantly reduced post RAD induction. Our results suggest that RAD is an effective induction regimen before ASCT with beneficial effects on bone metabolism and angiogenesis.

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