Triplet vs. doublet drug regimens for managing multiple myeloma

Multiple Myeloma (MM) is a complex and heterogeneous plasma cell disorder. Sub-clones present before therapy and clonal evolution during therapy make this disease more resistant and finally refractory. These findings make us aware of the difficulty to target MM with few agents. Multi-drugs therapies allow us to target more pathways and more sub-clones both at diagnosis and in advanced disease.

In this review, the authors focus on the effectiveness and tolerability of three drug regimens (triplet) in comparison with two drug regimens (doublet) and discuss their implications in the present and future of MM therapy.

It has been demonstrated that triplet regimens are better than doublet in terms of response rate and PFS in newly diagnosed, relapsed-refractory MM and in most patient subgroups. Whether this translates into OS improvement needs further demonstration. However, achievement of MRD negativity in most newly diagnosed and, firstly, in a consistent proportion of relapsed-refractory MM patients is very encouraging in this respect. However, not all patients are able to tolerate all triplet combinations; therefore, the choice should be based on patient characteristics, besides disease features. Finally, cost of triplets may be an important limitation in some countries.