Treatment options for refractory/relapsed multiple myeloma: an updated evidence synthesis by network meta-analysis

Abstract

BackgroundThe refractory/relapsed multiple myeloma (RRMM) remains a big clinical challenge, due to its biological and clinical complexity. Leading hematologists have performed many randomized controlled trials (RCTs) worldwide, and their findings were summarized in a recently published network meta-analysis (NMA) but with certain limitations.Materials and methodsWe performed an updated NMA of RCTs related to RRMM treatment, focusing on efficacy measures including the nonresponse rate (NRR), time to progression (TTP), progression-free survival (PFS), and overall survival (OS). The PubMed database was searched. We extended the literature search strategy of a previous NMA to June 30, 2017 and included additional primary RCTs. The surface under the cumulative ranking curve (SUCRA) was calculated to rank the regimens. A weighted-average method was used to rank the regimens by summarizing SUCRAs across different outcome measures.ResultsFinally, a total of 24 RCTs were included in this updated NMA. According to the result, the combination of daratumumab, lenalidomide, and dexamethasone showed better efficacy than other regimens in terms of NRR, TTP, and PFS (NRR: odds ratio [OR] =0.046, 95% credible interval [CrI] =[0.024, 0.085]; TTP: hazard ratio [HR] =0.14, 95% CrI =[0.092, 0.2]; PFS: HR =0.12, 95% CrI =[0.077, 0.18], compared with dexamethasone singlet). The combination of ixazomib, lenalidomide, and dexamethasone showed better efficacy than other regimens in terms of OS (HR =0.30, 95% CrI =[0.17, 0.54], compared with dexamethasone). The combination of daratumumab, lenalidomide, and dexamethasone ranked first in terms of overall efficacy (weighted average of SUCRAs =0.920).ConclusionThe combination of daratumumab, lenalidomide, and dexamethasone may currently be the most effective regimen in the population of RRMM patients. Triplet regimens containing daratumumab, ixazomib, carfilzomib, or elotumumab plus lenalidomide and dexamethasone can be recommended as first-line therapies for RRMM patients.

Daratumumab en el manejo del mieloma múltiple refractario o recidivante : metaanálisis en red.

“…Así mismo, el seguimiento en el tiempo de los desenlaces en ensayos clínicos que evalúan su efecto en combinación con otros tratamientos demuestra que los resultados favorables del daratumumab se incrementan con el tiempo y logran la reducción del riesgo de progresión del MM en un 69% 21 . Metaanálisis publicados recientemente reportan que, en efecto, los resultados del presente estudio son concordantes 22 . El elotuzumab es otro tratamiento que ha mostrado beneficios significativos en el manejo del MM refractario o recidivante 23 ; los resultados del presente estudio, sin embargo, reportan que el daratumumab tiene efectos superiores.…”

Upregulation of lncRNA NR_046683 Serves as a Prognostic Biomarker and Potential Drug Target for Multiple Myeloma

“…The accuracy of bioinformatics technique was verified based on big sample data, indicating that NR-046683 is a candidate target for the treatment of MM. However, the present study is a single-center small-sample-size experiment, from which the results had limitations in guiding clinical treatment (Luo et al, 2018). In the future, the sample size should be enlarged.…”

A practical and simplified management approach of multiple myeloma for primary healthcare specialist

“…It is also important to remember that multiple myeloma is a "multi-monoclonal" disease with more and more tumor clones expressed proportionally to duration of disease and number of therapeutic lines. The clinician must always find a fair compromise by proposing therapeutic associations that are sufficiently effective while taking into account the heavy therapeutic history that usually makes the patients even more fragile and their disease refractory [6].…”

“…About carfilzomib, very promising results were obtained in the ASPIRE and ENDEAVOR studies that compared respectively KRD (carfilzomib -lenalidomide -dexamethasone) versus RD and KD (carfilzomibdexamethasone) versus VD (bortezomib -dexamethasone). Finally, the main other treatments validated in R/R myeloma after at least 2 previous therapeutic lines are Elotuzumab, Ixazomib, Pomalidomide and Panobisnostat, with for the last 3 treatments a great advantage of convenience due to their oral route of administration (Figure 3) [6,10].…”