Discussion
MM, nonhematological adverse reactions
MYELOMA
This retrospective study highlights the real-world efficacy, feasibility, and tolerability of sequential therapy with bortezomib-based triplet regimens without lenalidomide (PXD) followed by continuous Rd treatment in patients with NDMM. We speculate that PI-based triplet regimens as initial therapy followed by IMIDs and dexamethasone as continuous treatment may be superior to PI-based continuous therapy. Sequential administration of bortezomib and lenalidomide during different stages of treatment may bring more benefit for the patients than only one of the new agents that was used during the initial and continuous treatment.In our study, the Rd cohort achieved a deeper treatment response and better survival outcomes than the Vd continuous treatment group. The combination of different mechanisms of PIs and immunomodulatory drugs may explain the difference. The mechanism of action of lenalidomide includes degradation of the transcription factors Ikaros (IKZF1) and Aiolos (IKZF3), which act as central transcription factors regulating various genes involved in the survival of myeloma cells. In addition, lenalidomide enhances the activation of various immune cells, including CD4, CD8, and NK T cells, while inhibiting regulatory T cells [Mateos et al. [Regarding the safety profile, Grade ≥ 3 drug-related AEs were observed in 30.0% of our cohort, which was lower than the 60% reported in the EVOLUTION trial (In conclusion, for newly diagnosed MM patients, sequential administration of bortezomib-based and lenalidomide-based therapy may not be worse than the VRd regimen with simultaneous application of two drugs. A sequential strategy could lead to fewer nonhematological adverse reactions and higher patient compliance. NDMM patients may also benefit from sequential administration of bortezomib and lenalidomide due to combining the therapeutic advantages of proteasome inhibitors and immunomodulators. It is not inferior to the VRd regimen, in which bortezomib and lenalidomide were applied simultaneously. Therefore, the sequential strategy is a feasible treatment strategy for NDMM patients in the real world and can be recommended.