Pooled analysis of the reports of carfilzomib/ixazomib combinations for relapsed/refractory multiple myeloma

Abstract

We sought to evaluate the activity and safety of carfilzomib-/ixazomib-containing combinations for patients with relapsed/refractory multiple myeloma (RRMM). We searched published reports including carfilzomib-/ixazomib-containing combinations for RRMM. Finally, we identified 11 prospective studies covering 2845 relapsed/refractory patients. Carfilzomib- and ixazomib-containing combinations respectively resulted in an impressive overall response rate (ORR 77 vs. 64%, P = 0.14), very good partial response or better (≥ VGPR 48 vs. 21%, P = 0.001), complete response or better (≥ CR 14 vs. 7%, P = 0.23), and clinical benefit rate (CBR 84 vs. 59%, P = 0.0002). Subgroup analysis showed that the carfilzomib (CFZ) +lenalidomide (LEN) + dexamethasone (DEX) triplet regimen resulted into similar response outcomes to those from CFZ + DEX doublet regimen in ORR (77 vs. 78%, P = 0.91), ≥VGPR (50 vs. 53%, P = 0.84), and ≥ CR (13 vs. 12%, P = 0.96) analysis in these previously heavily pretreated population. And, there were no statistically significant differences between IXA + LEN + DEX triplet regimen and CFZ + LEN + DEX triplet regimen in ORR (85 vs. 78%, P = 0.55), ≥ VGPR (37 vs. 53%, P = 0.19), and ≥ CR (18 vs. 12%, P = 0.70) analysis. There were favorable trend towards proteasome inhibitors (PIs) + IMiDs + DEX in comparison with PIs + alkylating agent + Dex in ORR (79 vs 49%, P < 0.00001), ≥ VGPR analysis (36 vs. 16%, P = 0.008), and ≥ CR (16 vs. 3%, P < 0.00001). Compared with current standard chemotherapy, carfilzomib containing combinations clearly improved overall survival (HR, 0.79; P = 0.01), progression free survival (HR, 0.61; P = 0.0001). Carfilzomib-/ixazomib-containing combinations produced clinical benefit for patients with R/RMM. PIs + IMiDs + DEX triplet regimens could be good options for such relapsed/refractory patients.

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