High risk cytogenetics were defined as del17p, t(4;14), t(14;16), 1q21 gain or amplification by fluorescence in situ hybridization....Len-combo regimens were either doublets (Len with dexamethasone [dex: n = 10], elotuzumab [n = 28] or ixazomib [n = 14]) or triplets (Len with bortezomib/dex [n = 10], ixazomib/dex [n = 10] or carfilzomib/dex [n = 6])...for patients with HR cytogenetic abnormalities other than 1q+ there was a trend towards better PFS with Len-combo (HR 0.59, CI 0.32-1.09, p = 0.09), without a difference in OS (HR: 0.79, CI: 0.37-1.65, p = 0.53)….In this single center retrospective analysis, intensification of post-transplant Len maintenance did not show an improvement in outcomes for HRMM patients. However, there was a trend towards improved PFS in patients with HR abnormalities other than 1q+.

High risk cytogenetics were defined as del17p, t(4;14), t(14;16), 1q21 gain or amplification by fluorescence in situ hybridization....Len-combo regimens were either doublets (Len with dexamethasone [dex: n = 10], elotuzumab [n = 28] or ixazomib [n = 14]) or triplets (Len with bortezomib/dex [n = 10], ixazomib/dex [n = 10] or carfilzomib/dex [n = 6])...for patients with HR cytogenetic abnormalities other than 1q+ there was a trend towards better PFS with Len-combo (HR 0.59, CI 0.32-1.09, p = 0.09), without a difference in OS (HR: 0.79, CI: 0.37-1.65, p = 0.53)….In this single center retrospective analysis, intensification of post-transplant Len maintenance did not show an improvement in outcomes for HRMM patients. However, there was a trend towards improved PFS in patients with HR abnormalities other than 1q+.

The overall response rate (ORR) was 73.0% in the IRD cohort vs 66.2% in the RD cohort….Median OS was significantly improved in the IRD cohort (36.6 months vs 26.0 months p=0.008); in patients with 1–3 prior relapses median OS was not yet reached for the IRD cohort (NR vs 27.1 months p=0.002). A higher percentage of patients in the IRD cohort were still alive at 6 months (88.9% vs 83.4%), 12 months (76.8% vs 71.5%), and 24 months (66.4% vs 52.7%),...High-risk features as defined by the presence at least one cytogenetic abnormality including t(4;14), t(14;16), or del(17p13) were present in 11.8% (15/127) patients in the IRD cohort and 8.8% (19/217) patients in the RD cohort. Among those patients in the IRD cohort whose disease was considered high-risk, one patient reached VGPR, six reached PR, four reached MR, two had stable disease (SD) and two progressed (PD).

Interphase fluorescence in situ hybridization (iFISH) was successful in 18 patients. High-risk cytogenetics (defined as the presence of t(4;14), 17p deletion, and 1q gain) were found in 11 patients (61.1%)….the overall response rate (partial response or better) in participants who had at least 3 cycles of treatment was 89% (23/26), with 5 Complete Responses (CR, 19.2%), 9 very good partial responses (VGPR, 34.6%), 9 partial responses (34.6%), and 3 Minimal Responses (MR, 11.5%)....The combination of ixazomib, lenalidomide, and dexamethasone is an effective and well-tolerated intervention in high-risk smoldering myeloma.