Evolution of Treatment Paradigms in Newly Diagnosed Multiple Myeloma

Elnair, Radowan; Holstein, Sarah A.

doi:10.1007/s40265-021-01514-0

Cited by 10 publications

(6 citation statements)

References 64 publications

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“…For example, lenalidomide/bortezomib/dexamethasone (RVD) can improve the survival of TIEMM significantly compared to lenalidomide/dexamethasone (Rd) ( 7 , 8 ). Besides, immunotherapy also made significant progress in MM ( 9 ), and research revealed that combination regimens such as daratumumab/lenalidomide/dexamethasone (DRd) and daratumumab/bortezomib/melphalan/dexamethasone (DVMP) achieved substantial efficacy in patients with TIEMM ( 10 ). Multiple guidelines recommend DRd, DVMP, and RVD as first-line treatment options for TIE-NDMM ( 4 , 11 ).…”

Section: Introductionmentioning

confidence: 99%

Daratumumab-based immunotherapy vs. lenalidomide, bortezomib and dexamethasone in transplant-ineligible newly diagnosed multiple myeloma: a systemic review

Tang,

Zhang,

Zheng

et al. 2024

Front. Oncol.

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BackgroundSince no randomized controlled trials have directly compared the efficacy and safety of immunotherapy with daratumumab versus lenalidomide/bortezomib/dexamethasone (RVD) in the frontline treatment of transplant-ineligible newly diagnosed multiple myeloma (TIE-NDMM), this study systematically reviewed the clinical studies regarding immunotherapy with daratumumab and RVD regimen in the treatment of TIE-NDMM to explore the optimization direction of the best first-line therapy.MethodsThe Cochrane Library, PubMed, Embase, and Web of Science databases were searched to collect studies on regimens containing daratumumab or RVD/RVD-lite for TIE-NDMM. Pooled and meta-analysis was then performed to compare the overall response rate (ORR), stringent complete remission (sCR) and CR rate, progression-free survival (PFS), overall survival (OS) and treatment-related discontinuation rate between daratumumab-containing immunotherapy regimen and RVD/RVD-lite regimen by using R 4.3.1 software.ResultsNine prospective clinical trials were included, including 1795 TIE-NDMM or NDMM without intent for immediate ASCT. Among them, 938 patients were treated with daratumumab-based immunotherapy and 857 with RVD/RVD-lite regimens. Meta-analysis results showed that The daratumumab-based regimen showed a significantly higher CR/sCR rate than RVD/RVD-lite for TIE-NDMM (47% vs. 24%, P<0.01). The median PFS of the daratumumab-based and RVD/RVD-lite groups were 52.6 months and 35.1 months respectively (HR 0.77, 95%CI, 0.66-0.90). The median OS of both groups was not reached, and there were no significant differences in OS between the two groups (HR 1.03, 95%CI, 0.86-1.23). The therapy discontinuation rate led by adverse events was significantly higher in the RVD/RVD-lite group than in the daratumumab-based regimen group for the TIE-NDMM (16% vs. 7%, P=0.03).ConclusionThis meta-analysis suggests that daratumumab-containing immunotherapy is superior to RVD in the depth of treatment efficacy, progression-free survival, and lower treatment-related discontinuation rates. Limited by the lack of head-to-head clinical trials, this conclusion needs to be verified by concurrent cohort studies.

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Section: Introductionmentioning

confidence: 99%

Daratumumab-based immunotherapy vs. lenalidomide, bortezomib and dexamethasone in transplant-ineligible newly diagnosed multiple myeloma: a systemic review

Tang,

Zhang,

Zheng

et al. 2024

Front. Oncol.

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“…In the past twenty years, integration of proteasome inhibitors (PI) and immunomodulatory drugs (IMiD) into the MM treatment has significantly improved the survival outcome of patients (3). To date, although MM is considered a largely incurable disease, the evolution of MM therapy is ongoing (4). In the mid-2010s, monoclonal antibodies (mAb) targeting CD38 and signaling lymphocytic activation molecule F7 (SLAMF7), i.e.…”

Section: Introductionmentioning

confidence: 99%

“… 3 Although MM is currently considered a largely incurable disease, the evolution of MM therapy is ongoing. 4 In the mid-2010s, monoclonal antibodies targeting CD38 and signaling lymphocytic activation molecule F7 (SLAMF7), i.e. daratumumab and elotuzumab, were incorporated into the standard of care, bringing MM treatment into a new era of immunotherapy.…”

Section: Introductionmentioning

confidence: 99%

BCMA loss in the epoch of novel immunotherapy for multiple myeloma: from biology to clinical practice

et al. 2022

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The treatment of multiple myeloma (MM) is evolving rapidly. In the past few years, chimeric antigen receptor (CAR) modified T-cell and bispecific antibody (BsAb) are bringing new treatment options to relapsed/refractory (RR) MM patients. Currently, B-cell maturation antigen (BCMA) has emerged as the most commonly used target of T-cell based immunotherapies for RRMM. Clinical data have demonstrated promising efficacy and manageable safety profile of both CAR T-cell and BsAb therapies in heavily pretreated RRMM. However, most patients suffer from relapses at later time points, and the resistance mechanism remains largely unknown. Theoretically, loss of antigen is a potential tumor intrinsic resistance mechanism against BCMA-targeted immunotherapies. Therefore, strategies to overcome this kind of drug resistance are needed for these patients. In this review, we will discuss the loss of BCMA in the new epoch of immunotherapy for MM.

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“…The most common of these disorders include chronic myeloid leukemia (CML), chronic lymphocytic leukemia (CLL), multiple myeloma (MM), and B-cell non-Hodgkin’s lymphomas (B-cell NHLs) [ 1 , 2 ]. Historically, the mainstays of therapy for these diseases have been chemotherapy, radiotherapy, and bone marrow transplantation (BMT) [ 3 , 4 , 5 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

Pathobiology and Therapeutic Relevance of GSK-3 in Chronic Hematological Malignancies

Martelli

Paganelli

Evangelisti

et al. 2022

Cells

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Glycogen synthase kinase-3 (GSK-3) is an evolutionarily conserved, ubiquitously expressed, multifunctional serine/threonine protein kinase involved in the regulation of a variety of physiological processes. GSK-3 comprises two isoforms (α and β) which were originally discovered in 1980 as enzymes involved in glucose metabolism via inhibitory phosphorylation of glycogen synthase. Differently from other proteins kinases, GSK-3 isoforms are constitutively active in resting cells, and their modulation mainly involves inhibition through upstream regulatory networks. In the early 1990s, GSK-3 isoforms were implicated as key players in cancer cell pathobiology. Active GSK-3 facilitates the destruction of multiple oncogenic proteins which include β-catenin and Master regulator of cell cycle entry and proliferative metabolism (c-Myc). Therefore, GSK-3 was initially considered to be a tumor suppressor. Consistently, GSK-3 is often inactivated in cancer cells through dysregulated upstream signaling pathways. However, over the past 10–15 years, a growing number of studies highlighted that in some cancer settings GSK-3 isoforms inhibit tumor suppressing pathways and therefore act as tumor promoters. In this article, we will discuss the multiple and often enigmatic roles played by GSK-3 isoforms in some chronic hematological malignancies (chronic myelogenous leukemia, chronic lymphocytic leukemia, multiple myeloma, and B-cell non-Hodgkin’s lymphomas) which are among the most common blood cancer cell types. We will also summarize possible novel strategies targeting GSK-3 for innovative therapies of these disorders.

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Evolution of Treatment Paradigms in Newly Diagnosed Multiple Myeloma

Cited by 10 publications

References 64 publications

Daratumumab-based immunotherapy vs. lenalidomide, bortezomib and dexamethasone in transplant-ineligible newly diagnosed multiple myeloma: a systemic review

Daratumumab-based immunotherapy vs. lenalidomide, bortezomib and dexamethasone in transplant-ineligible newly diagnosed multiple myeloma: a systemic review

BCMA loss in the epoch of novel immunotherapy for multiple myeloma: from biology to clinical practice

Pathobiology and Therapeutic Relevance of GSK-3 in Chronic Hematological Malignancies

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