Treatment Outcomes in Patients With Newly Diagnosed Multiple Myeloma Who Are Ineligible for Stem-Cell Transplantation: Systematic Review and Network Meta-analysis

Cao, Yaohua; Wan, Ning; Liang, Zhuoru; Xie, Jingmei; Wang, Sen; Lin, Tengfei; Zhang, Tiantian; Jiang, Jie

doi:10.1016/j.clml.2019.04.009

Cited by 10 publications

(14 citation statements)

References 42 publications

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“…In addition, Blommestein et al did not analyze the Da_RD_Da combination . The most recent NMA by Cao et al contains all available combinations, including daratumumab treatments . The main limitation of this study was in mixing heterogeneous populations, such as patients who are transplant candidates with those who are not transplant candidates, and elderly patients with the general population.…”

Section: Discussionmentioning

confidence: 98%

“…Not‐blinded clinical trials can be influenced by investigators and promoters, especially for outcomes with a margin of subjectivity such as PFS. Moreover, the lack of homogeneity of treatment schedules in nodes could translate into greater uncertainty of results, as has been seen in other first‐line NMAs for MM treatment in patients who are not transplant candidates . It is also necessary to consider the influence of different patient profiles on this indication according to several characteristics (age, staging, cytogenetic pattern, etc).…”

Section: Methodsmentioning

confidence: 99%

“…Although NMAs can be a very useful tool, their results should only be taken into consideration if clinical trials with similar characteristics have been selected. A frequent problem of NMAs in the first line of treatment for MM is that they include clinical trials with heterogeneous populations as candidate and non‐candidate patients for stem cell transplantation, or elderly patients (sometimes ≥ 75 years) and the general population. The transplant‐ineligible population includes patients over 65 years of age or with comorbidities that imply that such a risky intervention is not recommended, as seen in the inclusion criteria of clinical trials .…”

Section: Introductionmentioning

confidence: 99%

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Network meta‐analysis of first‐line treatments in transplant‐ineligible multiple myeloma patients

Gil‐Sierra

Gimeno‐Ballester

Fenix-Caballero

et al. 2020

European J of Haematology

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Objectives Multiple myeloma (MM) is a complex disease. Lack of direct comparisons among treatments and incorporation of new alternatives make it necessary to perform studies that allow for clinical decision‐making. A network meta‐analysis (NMA) was developed to evaluate the comparative efficacy among different therapeutic alternatives in newly diagnosed transplant‐ineligible MM patients. Methods MEDLINE® and EMBASE® were systematically searched up for these drugs: lenalidomide, thalidomide, bortezomib, and daratumumab. Comparative phase II‐III randomized clinical trials (RCTs) were included. Progression‐free survival (PFS) was selected as efficacy outcome. The NMA was developed using Bayesian methods. Fixed‐ and random‐effects models were assessed using deviance information criteria. Results The systematic search yielded 593 results. Ten RCTs were included. No differences were observed between fixed‐ and random‐effects models. The combination of daratumumab, bortezomib, melphalan, and prednisone showed the best HR in PFS (reference treatment). Along with this scheme, the best PFS results were obtained by combination of daratumumab, lenalidomide, and dexamethasone (HR 1.2, 95% CrI 0.64‐2.4) and bortezomib with lenalidomide and dexamethasone (HR 1.6, 95% CrI 0.81‐3.0). Conclusions Schemes with the best PFS results were daratumumab treatments and combination of bortezomib, lenalidomide, and dexamethasone, although the latter scheme has been analyzed in heterogeneous populations.

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Section: Discussionmentioning

confidence: 98%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Network meta‐analysis of first‐line treatments in transplant‐ineligible multiple myeloma patients

Gil‐Sierra

Gimeno‐Ballester

Fenix-Caballero

et al. 2020

European J of Haematology

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“…58 Rd (lenalidomide and dexamethasone), with other treatment regimens building upon this double as tolerated, is often strategy in fragile patients. [59][60][61] Reduced-dose triplet regimens such as RVD-lite have been developed for transplant-ineligible patients. 62 Just as with ASCT eligible candidates, there are several drug combinations using daratumumab which are currently being evaluated for use in transplant-ineligible patients.…”

Section: Asct Ineligible Patientsmentioning

confidence: 99%

<p>Evaluating Daratumumab in the Treatment of Multiple Myeloma: Safety, Efficacy and Place in Therapy</p>

Dima¹,

Dower²,

Comenzo³

et al. 2020

CMAR

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Despite the tremendous advances in the treatment of multiple myeloma, mortality remains significant, highlighting the need for new effective strategies. In recent years, daratumumab, a novel human monoclonal antibody, binding CD38, has dramatically improved outcomes either as monotherapy or in combination with traditional regimens. Originally approved for relapsed/refractory multiple myeloma, this breakthrough medication is now being used as frontline therapy in patients with newly diagnosed multiple myeloma regardless of transplant eligibility, with trials showing promising results. Its tolerable sideeffect profile and enhanced efficacy have led to its widespread incorporation into the management of multiple myeloma and further exploration about its use in other entities such as smoldering myeloma, MGUS, MGRS and amyloidosis. This comprehensive review will discuss daratumumab's mechanism of action and safety profile, as well as research which has defined its current approved indications, and ongoing clinical investigation that will define its future.

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“…VRd showed superior OS, but the analysis excluded daratumumab-based regimens given immaturity of OS data. 39 The efficacy of daratumumab is also being evaluated in other PI-based doublet regimens, specifically in frail patients with NDMM. The phase II HOVON 143 study is evaluating the efficacy of daratumumab in combination with ixazomib and low-dose dexamethasone in this subset of patients.…”

Section: Daratumumab In Transplant-ineligible Ndmmmentioning

confidence: 99%

Daratumumab in untreated newly diagnosed multiple myeloma

Abdallah

Kumar

2019

Therapeutic Advances in Hematology

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The treatment of multiple myeloma has evolved markedly in the last decade, but mortality remains high, emphasizing the need for more effective therapies. Daratumumab, a fully human monoclonal antibody targeting CD38, has shown clinical efficacy in relapsed/ refractory multiple myeloma both as monotherapy and in combination with other drugs, including novel agents. More recently, promising results have been reported in patients with untreated newly diagnosed multiple myeloma (NDMM). Clinical trials thus far have shown enhanced efficacy and tolerability of several daratumumab-based combinations in both transplant ineligible and eligible patients, without compromising transplant ability. However, benefit in high-risk subpopulations is still unclear. A subcutaneous formulation of daratumumab has been introduced to decrease the risk of infusion reactions, with preliminary results showing non-inferior efficacy. The antimyeloma activity of daratumumab is achieved through multiple mechanisms including direct, Fc-dependent, and immunomodulatory mechanisms. Enhanced efficacy of daratumumab in combination with immunomodulatory drugs and proteasome inhibitors is supported by preclinical data showing synergism. This review will focus on the role of daratumumab in untreated NDMM patients, highlighting the results of major clinical trials, and listing ongoing trials that are evaluating various daratumumab-based combinations in this setting.

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Treatment Outcomes in Patients With Newly Diagnosed Multiple Myeloma Who Are Ineligible for Stem-Cell Transplantation: Systematic Review and Network Meta-analysis

Cited by 10 publications

References 42 publications

Network meta‐analysis of first‐line treatments in transplant‐ineligible multiple myeloma patients

Network meta‐analysis of first‐line treatments in transplant‐ineligible multiple myeloma patients

<p>Evaluating Daratumumab in the Treatment of Multiple Myeloma: Safety, Efficacy and Place in Therapy</p>

Daratumumab in untreated newly diagnosed multiple myeloma

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