Pb2095: elotuzumab or daratumumab in combination with pomalidomide and dexamethasone (epd and dpd) in relapsed refractory multiple myeloma (rrmm): a network meta-analysis

Topic: 14. Myeloma and other monoclonal gammopathies - Clinical Background: Multiple myeloma (MM) is an incurable, life-limiting disease that accounts for approximately 10% of hematological malignancies1. Elotuzumab is a monoclonal antibody intended to improve outcomes in relapsed/refractory MM (RRMM) and has been investigated in combination with pomalidomide plus dexamethasone (dex) (EPd) in the ELOQUENT-3 trial. EPd has been compared against key treatment options in third or subsequent line therapy in Farrell et al.2. Daratumumab in combination with pomalidomide and dex (DPd) has been investigated in the APOLLO and MM-014 trials. Aims: A systematic literature review (SLR) and network meta-analysis (NMA) were conducted to determine the comparative effectiveness of EPd and DPd with other relevant options for the Brazilian private market for 3L+ RRMM. Methods: An SLR based on searches of Medline, Embase, PubMed and the Cochrane Library was conducted to identify randomised controlled trials of treatments for RRMM. Relevant comparators were identified based on ESMO guidelines. Data from trials that met the SLR’s inclusion criteria and the most recent data from ELOQUENT-3 were extracted. The final list of treatments included in the NMA are those available in Brazil. There are two distinct, separate networks: those with pomalidomide + dex (Pd) as a control arm (EPd, DPd, isatuximab + pomalidomide + dex (IsaPd)), and those with a bortezomib + dex (Vd) or carfilzomib + dex (Kd) control arm (daratumumab + bortezomib + dex (DVd), isatuximab + carfilzomib + dex (IsaKd), daratumumab + carfilzomib + dex (DKd)). To connect these networks, an external Vd arm was generated for EloPd though a propensity score matching, using patient-level data from the ELOQUENT-3 and OPTIMISMM (Pvd vs Vd) trials. The impact of fixed duration Vd in the control arm of CASTOR was adjusted to the Vd arm of OPTIMISMM using a matched adjusted indirect comparison for progression free survival (PFS) (results reported in the following section correspond to 24 weeks onwards). Propensity score matching and adjustment on Vd are described in Farrell et al.1 Results: EloPd and DPd were found to be as effective as the other comparators. As shown in Table 1, the estimated HRs (hazard ratios) for EPd ranged from 0.59 [0.37; 0.93] for the comparison versus Pd to 1.31 [0.63; 2.70] versus DKd for overall survival (OS); and ranged from 0.51 [0.32; 0.80] for the comparison versus Vd to 1.80 [0.88; 3.68] versus IsaKd for PFS. Comparisons were significant against Vd (for PFS) and Pd (for OS and PFS). The estimated HRs for DPd ranged from 0.91 [0.61; 1.35] for the comparison versus Pd to 2.03 [0.78; 5.29] versus DKd for OS; and ranged from 0.63 [0.47; 0.85] for the comparison against Pd to 2.33 [0.90; 5.53] versus IsaKd for PFS. The comparison was significant against Pd for PFS. Summary/Conclusion: NMA evidence suggests that there is no notable difference between EPd and DPd and other established and new regimens (DVd, Kd, IsaKd and DKd) in OS and PFS in patients with RRMM. 1Rajkumar SV. Multiple myeloma: 2022 update on diagnosis, risk stratification, and management. Am J Hematol. 2022 Aug;97(8):1086-1107. 2Farrell et al. Elotuzumab in combination with pomalidomide and dexamethasone (EPd) in Relapsed Refractory Multiple Myeloma (RRMM): a network meta-analysis. IMS (2022).Keywords: Relapse, Multiple myeloma, Meta-analysis, Refractory