Addressing unmet medical needs in maintenance treatment for newly diagnosed multiple myeloma (NDMM).

e20049 Background: In NDMM, following response to primary therapy, maintenance may delay progression and prolong OS; however, maintenance is not an established treatment option worldwide; lenalidomide (R) is the only approved agent, and only post-ASCT. Methods: We reviewed published/ongoing phase 3 trials of current/emerging maintenance treatments to identify unmet needs and how these may be addressed. Results: Maintenance with R, bortezomib (V), or thalidomide (T) has been well-studied and offers differential benefit, leaving unmet needs in some populations. R post-ASCT prolongs PFS/OS but increases the risk of SPMs and shows a less pronounced benefit in some subgroups, e.g high-risk (HR) cytogenetics, high ISS stage. R has improved PFS but not OS in the non-ASCT setting. T prolongs PFS/OS but not in HR cytogenetics, and with notable toxicity. V has activity post-ASCT, including in HR cytogenetics, and in the non-ASCT setting, but has not been studied in a placebo-controlled setting. Long-term use of these agents may be limited by short- and long-term toxicity and the treatment burden of repeated IV/SC administration. There is a need for a therapy that can be dosed for an extended time without cumulative/late-onset toxicity or emergence of resistant clones and that can offer benefit in all patients, including HR subgroups. Ongoing studies of ixazomib (I), carfilzomib (K), and daratumumab (D) (Table) may address some of these needs. Long-term I/K/D-based treatment results in deepening responses and improved outcomes, including in HR subgroups; oral ixazomib potentially offers convenient, feasible long-term proteasome inhibitor therapy with a manageable toxicity profile. Conclusions: Current maintenance therapies improve patient outcomes, with some limitations. Emerging therapies may offer a feasible approach due to manageable long-term toxicity profiles and convenience, especially oral agents. Ongoing phase 3 maintenance trials Agent Study Design NCT number I TOURMALINE-MM3 I vs placebo, post-ASCT NCT02181413 TOURMALINE-MM4 I vs placebo, non-ASCT NCT02312258 GEM2014MAIN I-R vs R, post-ASCT NCT02406144 K Uni of Chicago KRd vs R, post-ASCT NCT02659293 D Cassiopeia D vs observation, post-ASCT NCT02541383