Advancing multiple myeloma therapy: A systematic analysis of corticosteroids and monoclonal antibodies as dual therapeutic agents

Table 1 Characteristics of selected studies

Ref.	Year	Sample size	Study type	Interventions	Outcomes	Key findings
Voorhees et al[10]	2020	207	RCT	Daratumumab + RVd vs RVd	Improved response rates and PFS	sCR rate 424% vs 32.0%
Kumar et al[8]	2020	1087	RCT	Carfilzomib + Rd vs Bortezomib + Rd	No PFS benefit for Carfilzomib over Bortezomib	No significant PFS benefit observed
Lonial et al[9]	2015	646	RCT	Elotuzumab + Rd vs Rd	Improved PFS and response rates with Elotuzumab	PFS improved by approximately 4.5 months (HR 0.70)
Bringhen et al[4]	2018	54	RCT	Weekly Carfilzomib + Cyclophosphamide + Dex	High response rates with Carfilzomib	ORR > 85%
Facon et al[7]	2019	737	RCT	Daratumumab + Rd vs Rd	Significant PFS and ORR improvement with Daratumumab	PFS improved by 13.5 months
Dimopoulos et al[6]	2016	569	RCT	Daratumumab + Rd vs Rd	Improved PFS with Daratumumab	Median PFS: 44.5 vs 18.4 months (HR 0.37)
Palumbo et al[5]	2016	498	RCT	Daratumumab + Bortezomib + Dex vs Bortezomib + Dex	Significantly longer PFS with Daratumumab	Daratumumab group had a 61% risk reduction (HR 0.39)
Facon et al[2]	2007	447	RCT	MPT vs MP vs MEL100	MPT superior to MP in OS	OS improved with MPT arm (P < 0.05)
Richardson et al[3]	2003	202	RCT	Bortezomib	Bortezomib effective in refractory MM	Significant ORR in heavily pretreated patients
Rajkumar et al[1]	2010	445	RCT	Lenalidomide + Low-dose Dex vs High-dose Dex	Better OS and lower toxicity with low-dose Dex	Low-dose Dex improved OS and had fewer AEs
Jakubowiak et al[15]	2021	22	RCT	Daratumumab + Carfilzomib + Lenalidomide + Dex	Improved outcomes, high response rates	VGPR or better: 100%
Richardson et al[12]	2019	559	RCT	Pomalidomide + Bortezomib + Dex vs Bortezomib + Dex	Improved PFS in the Pomalidomide group	PFS improved by 4.1 months (11.2 vs 7.1 months)
Moreau et al[20]	2021	302	RCT	Isatuximab + Carfilzomib + Dex vs Carfilzomib + Dex	Improved PFS with Isatuximab combination	Median PFS: 35.7 vs 19.2 months
Sonneveld et al[18]	2023	709	RCT	Daratumumab + VRd vs VRd alone	Significant improvement in PFS	PFS: NR vs 62.4 months
Bumma et al[13]	2023	503	Cohort Study	Bortezomib-based vs Lenalidomide maintenance	Different maintenance strategies impact long-term outcomes	Individualized maintenance affects survival
Leypoldt et al[19]	2023	125	RCT	Isatuximab + Carfilzomib + Lenalidomide + Dex	High minimal residual disease negativity rates, long-term PFS benefit	Long-term PFS benefit in high-risk MM
Richardson et al[17]	2021	722	RCT	Ixazomib + Lenalidomide + Dex vs Placebo + Rd	No significant OS benefit, but some subgroup advantages	PFS benefit in some subgroups
Takezako et al[16]	2021	40	RCT	Once-weekly vs twice-weekly carfilzomib	Once-weekly dosing had better ORR and PFS	Improved tolerability with similar efficacy
Slade et al[23]	2023	25	RCT	Elotuzumab + Pomalidomide + Dexamethasone (EPd)	1-year PFS: 72%; median PFS: 19 months; safe regimen	Median PFS: 19 months
Joseph et al[22]	2024	1326	Cohort Study	Daratumumab + RVd vs RVd alone	Quadruplet therapy improves response and PFS	Improved VGPR and CR rates
Wang et al[21]	2017	32	Retrospective	Low-dose Lenalidomide + Dexamethasone	ORR: 71.9%, median PFS: 13 months, mild side effects	Mild side effects, effective in elderly
Bringhen et al[24]	2014	58	RCT	Carfilzomib + Cyclophosphamide + Dexamethasone	High response rates, PFS: 76%, OS: 87% at 2 years	PFS: 76%, OS: 87% at 2 years
Moreau et al[25]	2021	159	RCT	Teclistamab (BCMA × CD3 bispecific antibody)	ORR: 65%, VGPR: 58%, well tolerated, durable responses	ORR: 65%, VGPR: 58%
Dimopoulos et al[11]	2020	466	RCT	KdD (Carfilzomib, Dexamethasone, Daratumumab) vs Kd	KdD improved PFS (28.6 vs 15.2 months), manageable safety profile	PFS: 28.6 vs 15.2 months
Mateos et al[26]	2022	119	RCT	Lenalidomide + Dexamethasone vs Observation	Median TTP to MM: 9.5 vs 2.1 years, OS benefit with Rd	Median TTP: 9.5 vs 2.1 years
Bahlis et al[14]	2024	112	RCT	DPd (Pomalidomide + Daratumumab + Dexamethasone)	ORR: Favorable OS, median 56.7 months; no new safety signals	Median OS: 56.7 months

sCR: Stringent complete response; VGPR: Very good partial response; TTP: Time to progression; RCT: Randomized Controlled Trial; ORR: Overall response rate; OS: Overall survival; PFS: Progression-free survival; AEs: Adverse events; Cohort Study: Observational study following a group over time; Retrospective: Retrospective observational study; RVd: Lenalidomide (Revlimid) + Bortezomib (Velcade) + Dexamethasone; Rd: Lenalidomide + Dexamethasone; VRd: Bortezomib (Velcade) + Lenalidomide + Dexamethasone; Kd: Carfilzomib + Dexamethasone; KdD: Carfilzomib + Dexamethasone + Daratumumab; DPd: Daratumumab + Pomalidomide + Dexamethasone; EPd: Elotuzumab + Pomalidomide + Dexamethasone; MPT: Melphalan + Prednisone + Thalidomide; MP: Melphalan + Prednisone; MEL100: High-dose Melphalan 100 mg/m²; Dex: Dexamethasone; CR: Complete response; BCMA: B-cell maturation antigen; CD3: Cluster of Differentiation 3.

Table 2 Quality assessment for randomized controlled trials (Cochrane risk of bias)

Ref.	Random bias	Blinding bias	Deviations from intended interventions	Missing outcome data	Outcome measurement bias	Selective reporting bias	Overall risk of bias
Voorhees et al[10]	Low	Low	Low	Low	Low	Low	Low
Kumar et al[8]	Low	Low	Low	Low	Low	Low	Low
Lonial et al[9]	Low	Moderate	Low	Moderate	Low	Low	Moderate
Bringhen et al[4]	Low	Moderate	Low	Low	Low	Low	Low
Facon et al[7]	Low	Low	Low	Low	Low	Low	Low
Dimopoulos et al[6]	Low	Low	Low	Low	Low	Low	Low
Palumbo et al[5]	Low	Moderate	Low	Moderate	Low	Low	Moderate
Facon et al[2]	Low	Moderate	Low	Low	Low	Low	Low
Richardson et al[3]	Low	Low	Low	Low	Low	Low	Low
Rajkumar et al[1]	Low	Low	Low	Low	Low	Low	Low
Jakubowiak et al[15]	Low	Low	Low	Low	Low	Low	Low
Richardson et al[12]	Low	Low	Low	Low	Low	Low	Low
Moreau et al[20]	Low	Moderate	Low	Moderate	Low	Low	Moderate
Sonneveld et al[18]	Low	Moderate	Low	Low	Low	Low	Low
Leypoldt et al[19]	Low	Low	Low	Low	Low	Low	Low
Richardson et al[17]	Low	Low	Low	Low	Low	Low	Low
Takezako et al[16]	Low	Moderate	Low	Moderate	Low	Low	Moderate
Slade et al[23]	Low	Moderate	Low	Low	Low	Low	Low
Bringhen et al[24]	Low	Low	Low	Low	Low	Low	Low
Moreau et al[25]	Low	Low	Low	Low	Low	Low	Low
Dimopoulos et al[11]	Low	Low	Low	Low	Low	Low	Low
Mateos et al[26]	Low	Low	Low	Low	Low	Low	Low
Bahlis et al[14]	Low	Moderate	Low	Moderate	Low	Low	Moderate

Table 3 Quality assessment for observational/cross-sectional studies (Newcastle-Ottawa scale)

Ref.	Selection (4)	Comparability (2)	Outcome (3)	Total score
Bumma et al[13]	4	2	3	9
Joseph et al[22]	4	2	3	9
Wang et al[21]	4	2	3	9