Role of Stem Cell Transplantation in Multiple Myeloma

Abstract

Autologous stem cell transplantation (auto-SCT) has been the standard of care in eligible newly diagnosed multiple myeloma (MM) patients. Outcomes of patients with MM have improved significantly due to the advent of several novel drugs. Upfront use of these drugs in induction therapy has significantly increased the rate and depth of responses that have translated into longer remission and survival. This has now raised a debate regarding the role and relevance of auto-SCT in the management of myeloma. However, clinical trials have confirmed the utility of auto-SCT even in the era of novel drugs. Tandem auto-SCT followed by maintenance has shown a progression-free survival (PFS) benefit in high-risk MM, and hence can be considered in young and fit patients with high-risk disease. Auto-SCT has the advantages of resetting the bone marrow microenvironment, short-lived toxicity compared to the long-term physical and financial toxicities of continued chemotherapy in the absence of SCT, very low transplant-related mortality (TRM) in high volume centers, and providing longer disease-free survival when followed by maintenance therapy. Allogeneic SCT is one potentially curative option for MM, albeit with an increased risk of death due to high TRM. Strategies to modulate the graft-versus-host disease (GVHD) while maintaining or improving the graft-versus-myeloma (GVM) effect could place allogeneic SCT back in the treatment armamentarium of MM.

Spotlight on Melphalan Flufenamide: An Up-and-Coming Therapy for the Treatment of Myeloma

“…The inclusion of these novel therapies into the autologous stem-cell transplantation (ASCT) paradigm as consolidation and comprising induction and maintenance therapies has further improved clinical outcomes. [20][21][22][23][24] This model represents a mandatory choice for young patients and eligible elderly fit MM patients. 20 Moreover, some strategies, ie, continuous versus temporally defined treatments, contributed to further improving the natural history of MM patients.…”

“…[20][21][22][23][24] This model represents a mandatory choice for young patients and eligible elderly fit MM patients. 20 Moreover, some strategies, ie, continuous versus temporally defined treatments, contributed to further improving the natural history of MM patients. Nevertheless, it remains reasonably tricky the inadequacy of trials focusing on crucial questions, such as the delineation of ideal treatment sequencing approaches in MM patients' homogeneous cohorts.…”

“…31 However, while some achievements, ie, deep responses, are debating whether ASCT should be considered mandatory for eligible newly diagnosed patients, 32 high-dose L-PAM remains the standard conditioning regimen in ASCT for MM eligible patients. 20 The pharmacologic selection of alkylating oligopeptides recognized melphalan flufenamide, as a new, more potent anti-tumor drug than L-PAM, although with an equal alkylating aptitude. [33][34][35] Melflufen, a first-in-class peptide-drug conjugate (PDC), enters neoplastic cells effortlessly due to lipophilicity and targets aminopeptidases within the cell, ultimately explaining its higher tumor cell, 36 thus offering a superior cost-benefit ratio than that attained with L-PAM.…”

“…The inclusion of these novel therapies into the autologous stem-cell transplantation (ASCT) paradigm as consolidation and comprising induction and maintenance therapies has further improved clinical outcomes. 20–24 This model represents a mandatory choice for young patients and eligible elderly fit MM patients. 20 …”

“… 20–24 This model represents a mandatory choice for young patients and eligible elderly fit MM patients. 20 …”