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The efficacy and safety of the triplet combination lenalidomide, doxorubicin, and dexamethasone (RAD) are well known in patients with relapsed/refractory multiple myeloma (MM), however, data are limited for patients with newly diagnosed multiple myeloma (NDMM) who are eligible for autologous stem cell transplantation (ASCT).1 Lenalidomide has been shown to exert its function through the inhibition of interactions between myeloma and stromal cells, however, the effect of RAD on bone metabolism and angiogenesis is largely unknown.2
This open-label, non-comparative, non-randomized phase II study (NCT02471820), conducted by Evangelos Terpos and colleagues, aimed to evaluate the efficacy and safety of the RAD regimen as an induction protocol in patients with transplant-eligible symptomatic NDMM, as well as examining the effect on bone metabolism and angiogenic cytokine levels.3 Patients with symptomatic NDMM (n = 45; median age = 56 years; range, 37–69) were treated with a RAD induction regimen (lenalidomide [25 mg daily, days 1–21]; doxorubicin [9 mg/m2, days 1–4]; dexamethasone [40 mg, days 1, 8, 15, and 22]) for four cycles of 28-days each, prior to ASCT. Following ASCT, patients did not receive a consolidation or maintenance regimen. The primary endpoint of the study was overall response rate (ORR) to RAD regimen. Secondary endpoints included progression-free survival (PFS), time to disease progression (TTP), and safety assessment.
In conclusion, the RAD induction regimen prior to ASCT is effective and has a tolerable safety profile in patients with transplant-eligible NDMM. Moreover, RAD reduced bone resorption, increased bone formation and reduced circulating angiogenic cytokines, suggesting an impact on the tumor microenvironment. Further studies are needed to validate the therapeutic effect of this induction regimen on disease status, bone remodeling, and angiogenesis.
References
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