EFFICACY AND SAFETY OF DARATUMUMAB IN NEWLY DIAGNOSED TRANSPLANT-ELIGIBLE MULTIPLE MYELOMA: A SYSTEMATIC REVIEW AND META-ANALYSIS
- 1Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, RS, Brasil
- 2Universidade Cesumar, Maringá, PR, Brazil
- 3Hospital São Lucas,Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, RS, Brazil
Abstract
Background: Daratumumab has expanded the therapeutic options for patients with newly diagnosed multiple myeloma who are eligible for transplantation. This review evaluated its efficacy and safety through a systematic synthesis of the available evidence. Methods: A systematic review with meta-analysis was conducted following PRISMA recommendations. The PubMed, Embase, Scopus, Web of Science, and Cochrane Library databases were searched, including 16 clinical trials comprising 2,429 patients that compared daratumumab-containing regimens with standard treatment in transplant-eligible patients with newly diagnosed multiple myeloma. The meta-analysis was performed using R software (meta package), applying a random-effects model (REML), the Mantel-Haenszel method for binary outcomes, and inverse variance for hazard ratios, with 95% confidence intervals. Results: The analyses demonstrated a consistent benefit of incorporating daratumumab across all treatment phases. In the meta-analysis of minimal residual disease (MRD) negativity after consolidation, including the CASSIOPEIA and GRIFFIN studies (n=1,292), daratumumab-containing regimens significantly increased the likelihood of achieving MRD negativity compared with standard regimens (odds ratio [OR]=2.91; 95% CI: 1.60–5.29; p=0.0005), albeit with moderate heterogeneity (I²=73.1%), likely related to differences in induction regimens and study designs. Furthermore, the analysis of sustained MRD for ≥12 months, combining the GRIFFIN and AURIGA studies (n=407), demonstrated an even more pronounced benefit, with nearly a five-fold increase in the chance of maintaining MRD negativity (OR=4.69; 95% CI: 2.65–8.31; p<0.0001), with no heterogeneity between studies (I²=0%), highlighting high consistency of the results. Considering the methodological differences in randomization timing, progression-free survival (PFS) was analyzed in two independent meta-analyses. In the frontline strategy, including CASSIOPEIA Part 1, GRIFFIN, and PERSEUS (n=2,001), daratumumab-based regimens reduced the risk of disease progression or death by approximately 49% (hazard ratio [HR]=0.51; 95% CI: 0.39–0.66; p<0.0001), with low heterogeneity (I²=35%). Similarly, in the post-transplant maintenance strategy, combining CASSIOPEIA Part 2 and AURIGA (n=1,086), a reduction of approximately 51% in the risk of progression or death was observed (HR=0.49; 95% CI: 0.41–0.59; p<0.0001), with no heterogeneity (I²=0%). Collectively, these findings demonstrate consistent clinical benefit both in depth of response and in disease control throughout treatment. Regarding safety, the studies showed a favorable profile, with no new relevant toxicity signals; pneumonia and respiratory infections were the most frequently reported serious adverse events, without compromising the feasibility of autologous transplantation or hematopoietic stem cell collection. Conclusion: The incorporation of daratumumab into the treatment of transplant-eligible patients with newly diagnosed multiple myeloma promotes greater depth of response, significantly increases rates of minimal residual disease negativity and sustainability, and reduces the risk of progression or death, while maintaining a favorable safety profile. These findings reinforce the role of daratumumab as a fundamental component of first-line treatment in this population.
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- Stem cell mobilization with G-CSF and on-demand plerixafor in newly diagnosed multiple myeloma patients treated with daratumumab: a single-center experience
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BibTeX
@article{almeida2026efficacy,
title = {{EFFICACY AND SAFETY OF DARATUMUMAB IN NEWLY DIAGNOSED TRANSPLANT-ELIGIBLE MULTIPLE MYELOMA: A SYSTEMATIC REVIEW AND META-ANALYSIS}},
author = {Isadora Medeiros ALMEIDA and Maria Fernanda Gonçalves Meirelles FERNANDES and Lucas Mariano PINHEIRO and Carolina Marsiglia LUCINI and Gustavo Almiron LOPES and Bruna Leão Mazzini PEREIRA and Flávia Penso BERGAMASCHI and Luiz Fernando Franzen VINADE NETO and Marina Fração PEREIRA and Jalise Wolski Oliveira ROMANOV},
journal = {Hematology, Transfusion and Cell Therapy},
year = {2026},
month = oct,
doi = {10.1016/j.htct.2026.107869},
url = {https://doi.org/10.1016/j.htct.2026.107869},
note = {CC BY},
}
RIS
TY - JOUR
TI - EFFICACY AND SAFETY OF DARATUMUMAB IN NEWLY DIAGNOSED TRANSPLANT-ELIGIBLE MULTIPLE MYELOMA: A SYSTEMATIC REVIEW AND META-ANALYSIS
AU - Isadora Medeiros ALMEIDA
AU - Maria Fernanda Gonçalves Meirelles FERNANDES
AU - Lucas Mariano PINHEIRO
AU - Carolina Marsiglia LUCINI
AU - Gustavo Almiron LOPES
AU - Bruna Leão Mazzini PEREIRA
AU - Flávia Penso BERGAMASCHI
AU - Luiz Fernando Franzen VINADE NETO
AU - Marina Fração PEREIRA
AU - Jalise Wolski Oliveira ROMANOV
PY - 2026
DA - 2026/10/23
JO - Hematology, Transfusion and Cell Therapy
DO - 10.1016/j.htct.2026.107869
UR - https://doi.org/10.1016/j.htct.2026.107869
AB - Background: Daratumumab has expanded the therapeutic options for patients with newly diagnosed multiple myeloma who are eligible for transplantation. This review evaluated its efficacy and safety through a systematic synthesis of the available evidence. Methods: A systematic review with meta-analysis was conducted following PRISMA recommendations. The PubMed, Embase, Scopus, Web of Science, and Cochrane Library databases were searched, including 16 clinical trials comprising 2,429 patients that compared daratumumab-containing regimens with standard treatment in transplant-eligible patients with newly diagnosed multiple myeloma. The meta-analysis was performed using R software (meta package), applying a random-effects model (REML), the Mantel-Haenszel method for binary outcomes, and inverse variance for hazard ratios, with 95% confidence intervals. Results: The analyses demonstrated a consistent benefit of incorporating daratumumab across all treatment phases. In the meta-analysis of minimal residual disease (MRD) negativity after consolidation, including the CASSIOPEIA and GRIFFIN studies (n=1,292), daratumumab-containing regimens significantly increased the likelihood of achieving MRD negativity compared with standard regimens (odds ratio [OR]=2.91; 95% CI: 1.60–5.29; p=0.0005), albeit with moderate heterogeneity (I²=73.1%), likely related to differences in induction regimens and study designs. Furthermore, the analysis of sustained MRD for ≥12 months, combining the GRIFFIN and AURIGA studies (n=407), demonstrated an even more pronounced benefit, with nearly a five-fold increase in the chance of maintaining MRD negativity (OR=4.69; 95% CI: 2.65–8.31; p<0.0001), with no heterogeneity between studies (I²=0%), highlighting high consistency of the results. Considering the methodological differences in randomization timing, progression-free survival (PFS) was analyzed in two independent meta-analyses. In the frontline strategy, including CASSIOPEIA Part 1, GRIFFIN, and PERSEUS (n=2,001), daratumumab-based regimens reduced the risk of disease progression or death by approximately 49% (hazard ratio [HR]=0.51; 95% CI: 0.39–0.66; p<0.0001), with low heterogeneity (I²=35%). Similarly, in the post-transplant maintenance strategy, combining CASSIOPEIA Part 2 and AURIGA (n=1,086), a reduction of approximately 51% in the risk of progression or death was observed (HR=0.49; 95% CI: 0.41–0.59; p<0.0001), with no heterogeneity (I²=0%). Collectively, these findings demonstrate consistent clinical benefit both in depth of response and in disease control throughout treatment. Regarding safety, the studies showed a favorable profile, with no new relevant toxicity signals; pneumonia and respiratory infections were the most frequently reported serious adverse events, without compromising the feasibility of autologous transplantation or hematopoietic stem cell collection. Conclusion: The incorporation of daratumumab into the treatment of transplant-eligible patients with newly diagnosed multiple myeloma promotes greater depth of response, significantly increases rates of minimal residual disease negativity and sustainability, and reduces the risk of progression or death, while maintaining a favorable safety profile. These findings reinforce the role of daratumumab as a fundamental component of first-line treatment in this population.
SN - 2531-1379
SN - 2531-1387
ER -