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Multiple myeloma (MM) is a hematologic disease characterized by the clonal expansion of malignant plasma cells that accumulate in the bone marrow, leading to osteolytic bone disease, hypercalcemia, anemia, and renal dysfunction. Daratumumab was the first monoclonal anti-CD38 antibody approved for the treatment of MM, initially in relapse/refractory settings and, more recently, for newly diagnosed patients. Increased first-line usage of daratumumab will also substantially change treatment approaches for patients with relapsed/refractory disease. Due to the cost and availability of bispecific T cell redirecting antibodies (BsAbs) and chimeric antigen receptor T cell therapy (CAR-T) in real-life settings in many countries, retreatment with daratumumab in subsequent lines of therapy might be a reasonable choice. Data regarding efficacy and optimal combinations of daratumumab retreatment are lacking, and here we provide a short literature review of available data. We identified only a small number of articles based on retrospective analysis of medical records in real-life settings. A strong consistency in results regarding response rates and treatment duration was noticed among mainly heavily pre-treated MM patients, with approximately half of patients achieving at least partial remission (PR) after retreatment with daratumumab-based protocol. The duration of treatment and time to the next treatment for retreatment episodes were considerable and consistent with clinical expectations for later lines of therapy. The analysis of data in this literature review indicates that daratumumab retreatment may provide meaningful clinical benefit to some patients with relapsed/refractory MM despite having prior exposure. However, further research is needed to identify clinical and biological parameters that may predict favorable responses to daratumumab retreatment. [ABSTRACT FROM AUTHOR]

In the MAIA study (median follow-up, 56.2 months), daratumumab plus lenalidomide and dexamethasone (D-Rd) significantly improved progression-free survival (PFS) and overall survival versus lenalidomide and dexamethasone (Rd) alone in transplant-ineligible newly diagnosed multiple myeloma (NDMM). In this post hoc analysis of clinically important subgroups in MAIA (median follow-up, 64.5 months), transplant-ineligible patients with NDMM were randomized 1:1 to D-Rd or Rd. The primary endpoint was PFS; secondary endpoints included overall response rate (ORR) and measurable residual disease (MRD)-negativity rate (10 -5 ). PFS favored D-Rd versus Rd in most subgroups, including patients aged ≥75 years (HR, 0.59; 95% CI, 0.44-0.79), frail patients (HR, 0.64; 95% CI, 0.48-0.85), patients with high-risk cytogenetics (HR, 0.59; 95% CI, 0.44-0.80), and patients with isolated gain(1q21) (HR, 0.36; 95% CI, 0.19-0.67). ORRs, MRD-negativity rates, and sustained (≥12 months) MRD-negativity rates were higher with D-Rd versus Rd across subgroups. In patients aged ≥75 years, rates of grade 3/4 and serious treatment-emergent adverse events (TEAEs) were similar for D-Rd and Rd, but discontinuation due to TEAEs was lower for D-Rd. Results support use of D-Rd for high-risk patients, supporting D-Rd as a standard of care for transplant-ineligible NDMM. This trial was registered at www.clinicaltrials.gov as NCT02252172., Competing Interests: Competing interests: PM served on an advisory board for and received honoraria from Janssen, Celgene, Amgen, AbbVie, Sanofi, and Oncopeptides. TF has nothing to disclose. SZU received research funding from Amgen, Array BioPharma, Bristol Myers Squibb, Celgene, GlaxoSmithKline, Janssen, Merck, Pharmacyclics, Sanofi, Seattle Genetics, SkylineDx, and Takeda; served in a consulting role for AbbVie, Amgen, Bristol Myers Squibb, Celgene, Edo Pharma, Genentech, Gilead, GlaxoSmithKline, Janssen, Oncopeptides, Sanofi, Seattle Genetics, Secura Bio, SkylineDx, Takeda, and TeneoBio; and served on a speakers bureau for Amgen, Bristol Myers Squibb, Janssen, and Sanofi. NB served in a consulting or advisory role for and received honoraria from AbbVie, Bristol Myers Squibb/Celgene, FORUS, Genentech, Janssen, Karyopharm, Pfizer, Sanofi, and Takeda; and received research funding from Pfizer and Celgene. NR served as a consultant for Bristol Myers Squibb, Janssen, Takeda, Amgen, and GlaxoSmithKline; and received research funding from bluebird bio. TP served as an advisor for Janssen, Celgene, Takeda, Oncopeptides, Genentech, CSL Behring, and AbbVie; and received research support from Janssen, Genmab, Celgene, Takeda, Oncopeptides, Genentech, AbbVie, and Roche. RZO received research funding from Asylia Therapeutics, Biotheryx, Heidelberg Pharma, CARsgen, Celgene/Bristol Myers Squibb, Exelixis, Janssen, Sanofi-Aventis, and Takeda; received honoraria from and served as a member on a board of directors or advisory committee for AbbVie, Biotheryx, Bristol Myers Squibb, Janssen, Karyopharm, Meridian Therapeutics, Monte Rosa Therapeutics, Neoleukin, Oncopeptides, Regeneron, Sanofi-Aventis, and Takeda; and holds stock in Asylia Therapeutics. SB served as a consultant and on a speakers bureau for Sanofi, Pfizer, and Bristol Myers Squibb. HN is an employee of Genmab. CH received honoraria from Janssen, Bristol Myers Squibb, Amgen, Takeda, and AbbVie. HQ served as a consultant for and received research funding from AbbVie, Bristol Myers Squibb, Karyopharm, Amgen, GlaxoSmithKline, and Antengene. HG received grants and/or provisions of Investigational Medicinal Product from Amgen, Array BioPharma/Pfizer, Bristol Myers Squibb/Celgene, Chugai, Dietmar Hopp Foundation, Janssen, Johns Hopkins University, Mundipharma, and Sanofi; received research support from Amgen, Bristol Myers Squibb, Celgene, GlycoMimetics, GlaxoSmithKline, Heidelberg Pharma, Roche, Karyopharm, Janssen, Incyte, Millennium Pharmaceuticals, Molecular Partners, Merck Sharp & Dohme, MorphoSys AG, Pfizer, Sanofi, Takeda, and Novartis; served on an advisory board for Amgen, Bristol Myers Squibb, Janssen, Sanofi, and Adaptive Biotechnologies; received honoraria from Amgen, Bristol Myers Squibb, Chugai, GlaxoSmithKline, Janssen, Novartis, Sanofi, and Pfizer; and received support for attending meetings and/or travel from Amgen, Bristol Myers Squibb, GlaxoSmithKline, Janssen, Novartis, Sanofi, and Pfizer. MO served as a consultant for Janssen. AP received honoraria from AbbVie, Amgen, Celgene/Bristol Myers Squibb, GlaxoSmithKline, Janssen, Sanofi, and Takeda; served as a member on a board or advisory committee for Amgen, Celgene/Bristol Myers Squibb, GlaxoSmithKline, Janssen, Pfizer, and Takeda; and received research funding from Takeda. CPV received honoraria from Janssen, Bristol Myers Squibb, Sanofi, FORUS, Pfizer, AbbVie, GlaxoSmithKline, and Amgen. KW received research funding from Amgen, Adaptive Biotechnologies, AstraZeneca, Bristol Myers Squibb/Celgene, BeiGene, Janssen, GlaxoSmithKline, Sanofi, Stemline, and Takeda; received honoraria from AbbVie, Amgen, Adaptive Biotechnologies, AstraZeneca, Bristol Myers Squibb/Celgene, BeiGene, Janssen, GlaxoSmithKline, Karyopharm, Novartis, Oncopeptides, Pfizer, Roche, Sanofi, Stemline, and Takeda; and received travel support from Janssen, GlaxoSmithKline, and Sanofi. MT has nothing to disclose. MM served on an advisory board for Celgene/Bristol Myers Squibb, Janssen, Takeda, Amgen, GlaxoSmithKline, and Sanofi; received research funding from Janssen and Takeda; and received accommodations from Janssen, Celgene/Bristol Myers Squibb, Takeda, Amgen, and Sanofi. LF received honoraria from Janssen, Sanofi, Amgen, and Takeda; and received funding from Janssen and Amgen. XL received honoraria, research support, and consulting fees from Amgen, Merck, Bristol Myers Squibb, GlaxoSmithKline, Janssen, Oncopeptides, Takeda, Roche, Novartis, AbbVie, Sanofi, Gilead, Pfizer, Harpoon Therapeutics, Regeneron, and iTeos. GW, HP, and FB are employees of Janssen and hold stock in Johnson & Johnson. MK and RC are employees of Janssen. SKK received research funding from AbbVie, Amgen, Allogene, AstraZeneca, Bristol Myers Squibb, CARsgen, GlaxoSmithKline, Janssen, Novartis, Roche-Genentech, Takeda, Regeneron, and Molecular Templates; participated in consulting or an advisory board (with no personal payments) for AbbVie, Amgen, Bristol Myers Squibb, Janssen, Roche-Genentech, Takeda, AstraZeneca, bluebird bio, Epizyme, Secura Bio, Monte Rosa Therapeutics, Trillium, Loxo Oncology, K36, Sanofi, and Arcellx; and participated in consulting or an advisory board (with personal payments) for Oncopeptides, BeiGene, Antengene, and GLH Pharma., (© 2025. The Author(s), under exclusive licence to Springer Nature Limited.)