Abstract
The introduction of high-dose therapy in the 1990s as well as the development of drugs such as thalidomide, lenalidomide, and bortezomib in the 2000s led to an impressive improvement in outcome of patients with multiple myeloma (MM) eligible for autologous stem cell transplantation (ASCT). Clinical trials conducted in the first ten years of the twenty-first century established as standard therapy for these patients a therapeutic approach including induction, single or double ASCT, consolidation, and maintenance therapy. More recently, incorporating second-generation proteasome inhibitors carfilzomib and monoclonal antibody daratumumab into each phase of treatment significantly improved the efficacy of ASCT in terms of measurable residual disease (MRD) negativity, Progression Free Survival (PFS), and Overall Survival (OS). The availability of techniques such as multiparameter flow cytometry (MFC) and next-generation sequencing (NGS) for MRD assessment allowed the design of MRD-based response-adjusted trials that will define, in particular, the role of consolidation and maintenance therapies. In this review, we will provide an overview of the most recent evidence and the future prospects of ASCT in MM patients.
Highlights
Multiple myeloma (MM), a clonal plasma cells hematologic malignancy, accounts globally for 0.9% of all cancers diagnosed; the incidence increased by 126% from 1990 to 2016, especially in the developed world, e.g., Australia, western Europe, and US, where in 2020 it accounted for 1.8% of all cancers
In transplant-eligible (TE) newly diagnosed MM (NDMM) patients, autologous stem cell transplantation (ASCT) remains the standard of care recommended by international guidelines such as by ASCO [7] and ESMO [8] since a significant benefit of ASCT vs. conventional therapy was demonstrated, in patients receiving “old” chemotherapies in the control arm [9,10,11,12,13,14], and in those treated with new triplet combinations including proteasome inhibitors (PIs) and immunomodulatory agents (IMiDs) [15,16,17,18,19]
The results showed that both groups eventually collected the minimum target required to perform a tandem transplant (≥4 million CD34+/Kg), even though the total average CD34+ yield was significantly higher in patients mobilized with cyclophosphamide and granulocyte colony-stimulating factor (G-CSF) [43]
Summary
Multiple myeloma (MM), a clonal plasma cells hematologic malignancy, accounts globally for 0.9% of all cancers diagnosed; the incidence increased by 126% from 1990 to 2016, especially in the developed world, e.g., Australia, western Europe, and US, where in 2020 it accounted for 1.8% of all cancers. A recent analysis of 4329 NDMM patients treated with autologous stem cell transplantation (ASCT) at the University of Arkansas from 1989 through 2018 demonstrated the possibility of curing a fraction of patients, ranging from 6.3% to 31.3%, depending on the year of treatment, with many patients who achieved normal life expectancies [4]. Another large series of patients treated in France in “real-life” studies confirmed these results, reporting a median OS longer than 10 years in patients who underwent ASCT between 2010 and 2014 [5]. We will summarize the main fixed points about ASCT in MM, highlighting the most recent data concerning tailored therapies and HR MM treatment
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