Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2024 Dec 10;8(23):5993-6002.
doi: 10.1182/bloodadvances.2024014139.

Quadruplet regimens for patients with newly diagnosed multiple myeloma: a systematic review and meta-analysis

Mohammad S Ebraheem  1 , Rajshekhar Chakraborty  2 , Bram Rochwerg  3   4 , Alissa Visram  5 , Ghulam Rehman Mohyuddin  6 , Christopher P Venner  7 , Irwindeep Sandhu  8 , Arleigh McCurdy  5 , Thierry Facon  9 , Maria-Victoria Mateos  10 , Hira Mian  1
Affiliations
Meta-Analysis

Quadruplet regimens for patients with newly diagnosed multiple myeloma: a systematic review and meta-analysis

Mohammad S Ebraheem et al. Blood Adv. .

Abstract

Quadruplet regimens (anti-CD38 monoclonal antibodies [mAbs] with proteasome inhibitor [PI] and immunomodulatory drugs [IMiDs]) are increasingly being investigated in newly diagnosed multiple myeloma (NDMM). The objective of our study was to conduct a systematic review and meta-analysis to measure the efficacy and toxicity of quadruplet regimens used in NDMM. Embase, MEDLINE, Web of Science, Cochrane Library, clinical trial registries, and meeting libraries from inception to 24 January 2024, in addition to American Society of Clinical Oncology conference abstracts 2024, were searched using terms reflecting multiple myeloma and components of the quadruplet regimen. Included studies were randomized controlled trials (RCTs) that compared backbone regimens consisting of a PI and IMiD vs the same regimen plus an anti-CD38 mAb in NDMM. We identified 7 RCTs including 3716 patients. Compared with triplets, quadruplets increase the overall response rate (ORR; relative risk [RR], 1.03; 95% confidence interval [CI], 1.01-1.05) and progression-free survival (PFS; hazard ratio [HR], 0.55; 95% CI, 0.46-0.66). Quadruplets increase the rates of minimal residual disease (MRD) negativity at 10-5 (RR, 1.39; 95% CI, 1.23-1.58) and 10-6 (RR, 1.62; 95% CI, 1.36-1.94). Quadruplets improve overall survival (OS; HR, 0.65; 95% CI, 0.53-0.79). There was a slight increase in the rates of grade 3 to 4 infections (RR, 1.22; 95% CI, 1.07-1.39) noted with quadruplets compared with triplets. Overall, in this meta-analysis, quadruplets were associated with improved efficacy including ORR, MRD negativity, PFS, and OS, with a slight increase in infection rates. Quadruplet regimens represent a new standard of care, particularly in transplant-eligible NDMM.

PubMed Disclaimer

Conflict of interest statement

Conflict-of-interest disclosure: R.C. reports consultancy for Janssen, Sanofi Pasteur, and Adaptive Biotechnologies. A.V. reports consultancy/honoraria from Janssen, Sanofi, and Apotex. C.P.V. reports honoraria from Takeda, Bristol Myers Squibb (BMS), Janssen, Pfizer, Sanofi, GlaxoSmithKline (GSK), AbbVie, and FORUS Therapeutics. I.S. reports honoraria from Celgene/BMS, Gilead/Kite, GSK, Sanofi, Janssen, BeiGene, FORUS Therapeutics, and Pfizer, and stock with IllumiSonics Inc. A.M. reports honoraria from Celgene, Janssen, Amgen, Takeda, Sanofi, and GSK. T.F. reports consultancy for Janssen, bms, Roche, and Takeda, and speakers' bureau fees from Janssen and BMS. M.-V.M. reports consultancy fees/honoraria from Janssen, Celgene/BMS, GSK, Sanofi, Amgen, Menarini-Stemline, AbbVie, and Pfizer. H.M. reports consultancy fees from Janssen, Celgene/BMS, GSK, Sanofi, Amgen, AbbVie, and Pfizer; research funding from Janssen and Pfizer; and is supported by an Early Career Award from Hamilton Health Sciences. The remaining authors declare no competing financial interests.

Figures

Figure 1.
Figure 1.
PRISMA flow diagram.
Figure 2.
Figure 2.
Survival outcomes. (A) PFS for quadruplet vs triplet therapy for NDMM. (B) OS for quadruplet vs triplet therapy for NDMM. SE, standard error.
See this image and copyright information in PMC

References

    1. Rajkumar SV. Multiple myeloma: 2022 update on diagnosis, risk stratification, and management. Am J Hematol. 2022;97(8):1086–1107. - PMC - PubMed
    1. Sive J, Cuthill K, Hunter H, et al. Guidelines on the diagnosis, investigation and initial treatment of myeloma: a British Society for Haematology/UK Myeloma Forum guideline. Br J Haematol. 2021;193(2):245–268. - PubMed
    1. Dimopoulos MA, Moreau P, Terpos E, et al. Multiple myeloma: EHA-ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Hemasphere. 2021;5(2):e528. - PMC - PubMed
    1. Moreau P, Hulin C, Perrot A, et al. Maintenance with daratumumab or observation following treatment with bortezomib, thalidomide, and dexamethasone with or without daratumumab and autologous stem-cell transplant in patients with newly diagnosed multiple myeloma (CASSIOPEIA): an open-label, randomised, phase 3 trial. Lancet Oncol. 2021;22(10):1378–1390. - PubMed
    1. Voorhees PM, Sborov DW, Laubach J, et al. Addition of daratumumab to lenalidomide, bortezomib, and dexamethasone for transplantation-eligible patients with newly diagnosed multiple myeloma (GRIFFIN): final analysis of an open-label, randomised, phase 2 trial. Lancet Haematol. 2023;10(10):e825–e837. - PubMed

MeSH terms

Substances