Herein, we summarize the novel clinical data for multiple myeloma (MM) that were presented in the 2019 Annual Meeting of the American Society of Hematology. Triplet regimens including lenalidomide-dexamethasone for high-risk smoldering MM are effective but longer follow-up data are needed. Among transplant-eligible, newly diagnosed MM (NDMM) patients, carfilzomib- and daratumumab-based combinations are promising as effective and safe induction regimens and do not impair stem cell collection. Maintenance with ixazomib results in prolonged progression-free survival (PFS) compared with placebo. Regarding transplant-ineligible NDMM patients, large phase III studies showed that the additional use of daratumumab in backbone first-line regimens provides deep responses and PFS prolongation, whereas dose-/schedule-adjusted lenalidomide-dexamethasone has similar efficacy and is more tolerable than continuous lenalidomide-dexamethasone. In the relapsed/refractory setting carfilzomib- and daratumumab-based regimens remain highly effective and safe treatments, whereas the introduction of venetoclax, isatuximab, atezolizumab, and oprozomib broadens the therapeutic options. Among heavily pretreated MM patients, selinexor and melflufen showed particularly encouraging results. Novel immunotherapeutic approaches including chimeric antigen receptor T cells against B-cell maturation antigen and bispecific antibodies constitute a promising alternative that remains to be evaluated in later-phase studies.