Achievement and Persistence of MRD Negativity with Anti-CD38-Based Regimens in Newly Diagnosed Multiple Myeloma: A Systematic Review and Network Meta-Analysis
- 1Haematology Unit, Renato Dulbecco Hospital, 88100 Catanzaro, Italy
- 2Department of Hematology-Oncology, Azienda Ospedaliera Renato Dulbecco, 88100 Catanzaro, Italy
Abstract
Background/Objectives: Anti-CD38 monoclonal antibody-based quadruplets have increased measurable residual disease (MRD) negativity rates in newly diagnosed multiple myeloma, questioning the incremental benefit of upfront autologous stem cell transplantation (ASCT). Methods: We performed a systematic review and frequentist random-effects network meta-analysis (NMA) of randomized trials reporting MRD negativity by treatment arm; sustained MRD (sMRD) negativity was analyzed by pairwise meta-analysis. Results: Seventeen trials (6293 patients; 13 strategies) were included. Anti-CD38–KRd (SUCRA 89.1%), anti-CD38–VRd + ASCT (88.0%) and anti-CD38–KRd + ASCT (86.5%) ranked highest for MRD negativity, with no statistically significant difference among them. No comparison between a strategy with and without ASCT reached statistical significance (VRd + ASCT vs. VRd: OR 1.72, 95% CI 0.95–3.10). There was no evidence of inconsistency, and rankings were consistent across sensitivity analyses. Adding an anti-CD38 antibody to the same backbone increased the odds of sMRD negativity in both transplant-eligible (OR 3.05, 95% CI 1.32–7.03) and transplant-ineligible populations (3.26, 2.18–4.88; p for interaction = 0.88). No sMRD data allowed a comparison between transplant and non-transplant quadruplet strategies. Conclusions: Anti-CD38-based quadruplets offer the highest probability of achieving MRD negativity and improve its persistence regardless of transplant eligibility, whereas the incremental contribution of ASCT in the quadruplet era remains uncertain.
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BibTeX
@article{carida2026achievement,
title = {{Achievement and Persistence of MRD Negativity with Anti-CD38-Based Regimens in Newly Diagnosed Multiple Myeloma: A Systematic Review and Network Meta-Analysis}},
author = {Giulio Caridà and Luca Scalise and Antonio Mosca and Laura De Fazio and Martina Costa and Matteo Molica and Marco Rossi},
journal = {Cancers},
year = {2026},
month = nov,
doi = {10.3390/cancers18213573},
url = {https://www.mdpi.com/2072-6694/18/21/3573},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Achievement and Persistence of MRD Negativity with Anti-CD38-Based Regimens in Newly Diagnosed Multiple Myeloma: A Systematic Review and Network Meta-Analysis
AU - Giulio Caridà
AU - Luca Scalise
AU - Antonio Mosca
AU - Laura De Fazio
AU - Martina Costa
AU - Matteo Molica
AU - Marco Rossi
PY - 2026
DA - 2026/11/06
JO - Cancers
DO - 10.3390/cancers18213573
UR - https://www.mdpi.com/2072-6694/18/21/3573
AB - Background/Objectives: Anti-CD38 monoclonal antibody-based quadruplets have increased measurable residual disease (MRD) negativity rates in newly diagnosed multiple myeloma, questioning the incremental benefit of upfront autologous stem cell transplantation (ASCT). Methods: We performed a systematic review and frequentist random-effects network meta-analysis (NMA) of randomized trials reporting MRD negativity by treatment arm; sustained MRD (sMRD) negativity was analyzed by pairwise meta-analysis. Results: Seventeen trials (6293 patients; 13 strategies) were included. Anti-CD38–KRd (SUCRA 89.1%), anti-CD38–VRd + ASCT (88.0%) and anti-CD38–KRd + ASCT (86.5%) ranked highest for MRD negativity, with no statistically significant difference among them. No comparison between a strategy with and without ASCT reached statistical significance (VRd + ASCT vs. VRd: OR 1.72, 95% CI 0.95–3.10). There was no evidence of inconsistency, and rankings were consistent across sensitivity analyses. Adding an anti-CD38 antibody to the same backbone increased the odds of sMRD negativity in both transplant-eligible (OR 3.05, 95% CI 1.32–7.03) and transplant-ineligible populations (3.26, 2.18–4.88; p for interaction = 0.88). No sMRD data allowed a comparison between transplant and non-transplant quadruplet strategies. Conclusions: Anti-CD38-based quadruplets offer the highest probability of achieving MRD negativity and improve its persistence regardless of transplant eligibility, whereas the incremental contribution of ASCT in the quadruplet era remains uncertain.
SN - 2072-6694
ER -