Kazandjian D, Hill E, Dew A, et al. - Novel triplet regimens, such as KRd (carfilzomib, lenalidomide, and dexamethasone) and lenalidomide maintenance therapy, when employed in the treatment of high-risk smoldering myeloma may modify the natural history of smoldering myeloma by significantly delaying development of end-organ disease. There is a need for randomized clinical trials to corroborate this favorable benefit-to-risk profile.

• This is a single-arm, single-center, phase 2 nonrandomized controlled trial wherein 54 patients (median age, 59 years [range, 40-79 years]) with a diagnosis of high-risk smoldering myeloma were treated with KRd followed by lenalidomide maintenance therapy.

• The minimal residual disease-negative complete response rate was 70.4%, with a median sustained span of 5.5 years (95% CI, 3.7 years to not estimable).

• There was low progression to multiple myeloma (9% at 8 years), and no deaths occurred.

• A total 21 patients (38.9%) suffered nonhematologic grade 3 adverse events, which included thromboembolism, rash, and lung infection, and no grade 4 events occurred.