Treatment of autologous stem cell transplant-eligible multiple myeloma patients: ten questions and answers

Abstract

F e r r a t a S t o r t i F o u n d a t i o nics and renal impairment. In the era of novel agents, the role of transplant itself is being questioned and trials are ongoing to establish whether transplant can be delayed until after relapse in some patients. The current ongoing studies are aimed towards improving the different steps of the procedure with the aim of further improving efficacy and tolerability. This review addresses a number of questions surrounding the different steps of the transplant procedure and summarizes the available research evidence as a basis for decision making. Is high-dose therapy plus autologous stem cell transplantation superior to conventional chemotherapy?The concept of high-dose therapy (HDT) plus autologous stem cell transplantation (ASCT) was developed in the 1980s. The objective of ASCT was to support highdose therapy (HDT) in order to reduce the duration and toxicity of severe myelosuppression. The Intergroupe Francophone du Myelome (IFM) was the first to conduct a randomized trial showing the superiority of HDT/ASCT over conventional chemotherapy in patients under 65 years of age regarding response rate, event-free survival (EFS) and overall survival (OS).1 These findings were confirmed seven years later in a larger study conducted by the UK Medical Research Council (MRC Myeloma VII trial). 2Following these results, HDT/ASCT became the standard of care in patients without severe comorbidities and under 65 years of age.Overall, 7 randomized studies have compared ASCT/HDT to conventional chemotherapy. 3 While EFS was superior with HDT/ASCT in 5 of 7 trials, OS was significantly prolonged in only 3 trials. These results were confirmed by a meta-analysis that showed a significant benefit for HDT/ASCT in terms of EFS but no benefit in terms of OS. 4 This was partly explained by the impact of ASCT at relapse in patients initially treated with conventional chemotherapy. Therefore, although the majority of myeloma experts recommend HDT/ASCT as part of initial therapy, some experts consider that delaying ASCT until relapse remains a valuable approach.Importantly, the use of HDT/ASCT was the major cause of OS improvement observed in younger patients before the introduction of novel agents, such as immunomodulatory drugs (IMIDs) and proteasome inhibitors. 5 However, despite the demonstrated efficacy of the procedure, relapses ultimately occurred in the vast majority of patients and long remissions (and possible cures) remained rare. The introduction of several new agents (thalidomide, lenalidomide and bortezomib) has substantially changed treatment strategies in the transplant setting. The addition of novel agents before and/or after HDT/ASCT has dramatically increased the post-ASCT complete response (CR) rate and the CR plus very good partial response (VGPR) rate.6,7 Maybe more importantly, the level of CR has been up-graded with the achievement of stringent CR (s-CR) with a normal κ/λ ratio (serum free light chain assessment), 8 of immunophenotypic CR (with multiparameter flow cytome...

First linevsdelayed transplantation in myeloma: Certainties and controversies

“…The lack of advantage observed in some cases in terms of OS is mainly do to the effective salvage therapy nowadays available, and to the possibility for patients to receive ASCT later in their disease history as a salvage treatment. For this reason some centres nowadays recommend ASCT only for those patients with high-risk features, whilst for standard risk patients a treatment option reserving ASCT for the time of relapse is considered acceptable [59][60][61] . In this contest it has to be emphasised, in patients for whom a delayed ASCT may be considered, the extreme importance of early stem cell collection and cryopreservation; an early stem cell collection is particularly important in those patients receiving lenalidomide based treatments [62,63] .…”

Developments in the Field of Myeloma in the Last Decade

“…Another three drug combination is comprised of two novel agents (bortezomib, thalidomide or lenalidomide) with dexamethasone-VTD, VRD, etc. [14,15]. Both approaches produce excellent responses; however, a recent trial showed that VRD producing the best response.…”

“…Older patients also could be candidates if one is in good biological health. Peripheral blood (PBSC) has completely replaced bone marrow as the source of stem cells [14]. It is safe with a mortality risk of 0-1% at most centers.…”

Multiple Myeloma: New Perspectives

“…The term "Autologous stem cell transplantation" refers to transplantation of a patient's own stem cells after chemotherapy. It is not curative, but prolongs the overall survival rate and produces complete remission [29]. Allogeneic stem cell transplantation means transplantation of a healthy person's stem cells into the affected patient which may have the potential for cure, but is used in a very low percentage of patients.…”