Improving overall survival and overcoming adverse prognosis in the treatment of cytogenetically high-risk multiple myeloma

Abstract

Multiple myeloma (MM) is a heterogeneous disease with certain genetic features [eg, t(4;14), del17p] associated with worse outcome. The introduction of thalidomide, lenalidomide, and bortezomib has dramatically improved the outlook for patients with MM, but their relative benefit (or harm) for different genetic patient subgroups remains unclear. Unfortunately, the small number of patients in each subgroup frequently limits the analysis of high-risk patients enrolled in clinical trials. Strategies that result in survival of high-risk genetic subgroups approximating that of patients lacking high-risk features are said to overcome the poor prognostic impact of these high-risk features. This outcome has been difficult to achieve, and studies in this regard have so far been limited by inadequate sample size. In contrast, strategies that compare the survival of high-risk genetic subgroups randomized to different treatment arms can identify approaches that improve survival. This type of analysis is clinically useful, even if the absolute gains do not improve outcomes to levels seen in patients without high-risk cytogenetics. Reviewing available data in high-risk MM from this perspective, it appears that bortezomib has frequently been associated with improved survival, whereas thalidomide maintenance has sometimes been associated with a shorter survival. (Blood. 2013;121(6):884-892)

Outcomes of unrelated cord blood transplantation in patients with multiple myeloma: a survey on behalf of Eurocord, the Cord Blood Committee of Cellular Therapy and Immunobiology Working Party, and the Chronic Leukemia Working Party of the EBMT

“…Other authors have previously shown the negative impact of high-risk abnormalities, such as t(4;14), t(14;16), t(14;20) and del17p, on survival outcomes in patients with newly diagnosed MM. 26,27 Similar findings were demonstrated in patients receiving front-line ASCT, in which high-risk cytogenetics was associated with worse outcomes 28 and unsustained CR at one year. 29 The prognostic impact of adverse cytogenetics on alloSCT outcome in MM is not well established.…”

“…haematologica | 2016; 101(9) tions, 27 a recent study on UCBT 19 showed no association between high-risk cytogenetic and poor outcomes. A possible explanation for these findings might be the different risk group classification of patients harboring del13q.…”

Phase 1 study of weekly dosing with the investigational oral proteasome inhibitor ixazomib in relapsed/refractory multiple myeloma

“…[16][17][18][19] Bortezomib has been combined with other MM drugs leading to several highly effective combination regimens. [11][12][13][14][15]20 In particular, bortezomib plays a critical role in the management of patients with genetically high-risk MM 14,[21][22][23] and patients with renal insufficiency. 24,25 The introduction of subcutaneous administration has improved convenience compared with the intravenous approach and substantially reduced the risk of peripheral neuropathy (PN), 26 a major limiting factor for long-term administration.…”

MicroRNA theragnostics for the clinical management of multiple myeloma

“…16,17 Although the precise molecular events that generate MM remain incompletely understood, our understanding of events that underlie its development have greatly advanced. 18 Moreover, patients' response to bortezomib-based regimens is highly variable, and drug resistance inevitably emerges even in patients who initially responded. The incidence and prevalence of MM are steadily rising in Western countries because of an aging population combined with the increased overall survival of patients with MM.…”