As our induction therapy in the approach of multiple myeloma (MM) keeps on changing, the character of the relapses is altering too. By moving from doublets over triplets to quadruplets in the induction schemes, and thus intensifying first-line therapies, relapses are very often postponed in time. Nevertheless, they are more resistant to chemotherapy and thus more difficult to treat. In vitro data confirm the increase of the mutational burden of the persistent myeloma cells after chemotherapy and even more after the administration of high dose melphalan, followed by autologous stem cell support (ASCT). This could be an argument to leave ASCT in the first-line treatment of MM in the upcoming future. Moreover, the common use of lenalidomide in maintenance will lead to more refractoriness to this molecule in the relapse setting. The same is of course true when other molecules – e.g. proteasome inhibitors – are used in the maintenance setting. If the addition of daratumumab in first-line would become the standard in induction, this will of course also influence the behaviour of RRMM.

(BELG J HEMATOL 2021;12(1):14-6)