Aiming for the cure in myeloma: Putting our best foot forward

Bar, Noffar; Firestone, Ross S.; Usmani, Saad Z.

doi:10.1016/j.blre.2023.101116

Cited by 3 publications

(2 citation statements)

References 154 publications

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“…However, the importance and feasibility of the personalization of therapy is growing [9][10][11]. In the context of increasingly active quadruplet induction regimens [29][30][31][32] and our growing understanding of the mutagenic effects of melphalan [24,[33][34][35][36], as well as no OS benefit having been demonstrated with HDM-ASCT in recent studies [23][24][25][26]37], the role of HDM-ASCT as a standard approach for all-comers in transplant-eligible NDMM is being challenged.…”

Section: Current Treatment Of Newly Diagnosed MM (Ndmm) and The Role ...mentioning

confidence: 99%

“…The disease more commonly affects males (~56% of cases) and is generally a disease of the elderly, with the median age at diagnosis in the United States being 69 years [3]. MM exhibits substantial heterogeneity at diagnosis and throughout the disease course associated with multiple disease-related and patient-related characteristics including disease stage [4,5], cytogenetic abnormalities [6], age, and frailty [7,8], providing the context for the drive to develop personalized treatment approaches [9][10][11]. Overall survival (OS) has increased markedly over the past four decades, with the 5-year survival rate in the United States more than doubling to 59.8% [3] and the median OS in younger, fitter patients reaching approximately 10 years [12].…”

Section: Introductionmentioning

confidence: 99%

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Upfront or Deferred Autologous Stem Cell Transplantation for Newly Diagnosed Multiple Myeloma in the Era of Triplet and Quadruplet Induction and Minimal Residual Disease/Risk-Adapted Therapy

Mo,

Hartley-Brown,

Midha

et al. 2023

Cancers

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The standards of care for the initial treatment of patients with newly diagnosed multiple myeloma (NDMM) who are eligible for high-dose melphalan and autologous stem cell transplantation (HDM-ASCT) include highly active triplet and quadruplet regimens based on proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies. These regimens are resulting in improved outcomes and increasingly high rates of minimal residual disease (MRD)-negative responses without HDM-ASCT as part of the upfront therapy. Furthermore, recent randomized studies have shown that, while transplant-based approaches as a frontline therapy result in significantly longer progression-free survival compared to non-transplant approaches, this has not translated into an overall survival benefit. Given these developments, and in the context of the treatment burden of undergoing HDM-ASCT, in addition to the acute toxicities and long-term sequelae of HDM, which are associated with the genotoxicity of melphalan, there is an increasing rationale for considering deferring upfront HDM-ASCT in select transplant-eligible patients and saving it as a treatment option for later salvage therapy. Here, we review the latest clinical trial data on upfront or deferred HDM-ASCT and on the activity of quadruplet induction regimens, including rates of MRD-negative responses, and summarize emerging treatment approaches in the upfront setting such as the use of MRD-directed therapy and alternatives to HDM-ASCT.

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Section: Current Treatment Of Newly Diagnosed MM (Ndmm) and The Role ...mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Upfront or Deferred Autologous Stem Cell Transplantation for Newly Diagnosed Multiple Myeloma in the Era of Triplet and Quadruplet Induction and Minimal Residual Disease/Risk-Adapted Therapy

Mo,

Hartley-Brown,

Midha

et al. 2023

Cancers

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A phase 1b/2 study evaluating efficacy and safety of MP0250, a designed ankyrin repeat protein (DARPin) simultaneously targeting vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF), in combination with bortezomib and dexamethasone, in patients with relapsed or refractory multiple myeloma

Knop,

Szarejko,

Grząśko

et al. 2024

eJHaem

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MP0250 is a designed ankyrin repeat protein that specifically inhibits both vascular endothelial growth factor A (VEGF‐A) and hepatocyte growth factor (HGF), aiming at potentiating cancer therapy by disrupting the tumour microenvironment. Encouraging results from a phase 1 trial of MP0250 in patients with solid tumours prompted further investigation in multiple myeloma (MM) as both MP0250 targets are reported to be drivers of MM pathogenesis.In this open‐label, single‐arm phase 1b/2 study (NCT03136653) in patients with proteasome inhibitor‐ and/or immunomodulatory drug‐relapsed or refractory MM, MP0250 was administered every 3 weeks with standard bortezomib/dexamethasone regimen.Thirty‐three patients received at least one dose of MP0250. The most frequent treatment‐related adverse events were arterial hypertension (58.1%), thrombocytopenia (32.3%), proteinuria (29.0%) and peripheral oedema (19.4%). Of the 28 patients evaluable for response (median age: 60 [range 44–75]), nine achieved at least partial response, corresponding to an overall response rate of 32.1% (95% confidence interval [CI]: 17.9%, 50.7%), with a median duration of response of 8 months (95% CI 5–NR). An additional three patients achieved minimal response and nine stable diseases as the best overall response. Overall median progression‐free survival was 4.2 months (95% CI 1.9–7.1).These findings are in line with the results of recent trials testing new agents on comparable patient cohorts and provide initial evidence of clinical benefit for patients with refractory/relapsed MM treated with MP0250 in combination with bortezomib/dexamethasone. Further clinical evaluation in the emerging MM treatment landscape would be required to confirm the clinical potential of MP0250.

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NT157 exhibits antineoplastic effects by targeting IRS and STAT3/5 signaling in multiple myeloma

de Queiroz,

Lima,

de Miranda

et al. 2024

Hematology, Transfusion and Cell Therapy

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Aiming for the cure in myeloma: Putting our best foot forward

Cited by 3 publications

References 154 publications

Upfront or Deferred Autologous Stem Cell Transplantation for Newly Diagnosed Multiple Myeloma in the Era of Triplet and Quadruplet Induction and Minimal Residual Disease/Risk-Adapted Therapy

Upfront or Deferred Autologous Stem Cell Transplantation for Newly Diagnosed Multiple Myeloma in the Era of Triplet and Quadruplet Induction and Minimal Residual Disease/Risk-Adapted Therapy

NT157 exhibits antineoplastic effects by targeting IRS and STAT3/5 signaling in multiple myeloma

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