Autologous Stem Cell Transplantation in Multiple Myeloma: Where Are We and Where Do We Want to Go?

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.

Current treatment paradigm and survival outcomes among patients with newly diagnosed multiple myeloma in China: a retrospective multicenter study

“…Similarly, patients in our study population who received ASCT also had better survival than patients who did not receive ASCT, and such benefits remained significant among patients with R-ISS II/III disease. With a median follow-up time of 58.7 months, the PFS and OS for our study population who did and did not receive ASCT were slightly lower compared with the results from prior clinical trial observations with a similar duration of follow-up 25 . In agreement with a previous study 29 , patients who achieved ≥ CR after ASCT demonstrated better survival than patients who only achieved VGPR or PR after ASCT.…”

“…In agreement with previous studies [21][22][23] , our study showed a greater treatment response in patients with novel agents treatment (e.g., PI-, PI+IMiD-, or IMiD-based regimens) compared to patients who received conventional therapy. In addition, ASCT is recommended for transplant-eligible NDMM patients for survival benefits, even among patients with HRCA [24][25][26][27][28] . Similarly, patients in our study population who received ASCT also had better survival than patients who did not receive ASCT, and such benefits remained significant among patients with R-ISS II/III disease.…”

Non‐cryopreserved peripheral blood stem cells as a safe and effective alternative for autologous transplantation in multiple myeloma

“…16 There is no standard storage time for refrigerated PBSC in studies with fresh autologous transplantation of MM, ranging from 24 to 144 h. 3,[18][19][20] Most studies comparing fresh and cryopreserved infusion have maintained fresh cells up to 48 h 3,4,11 and the increase of storage time must be clinically validated. 10 In our study, all fresh transplanted patients received PBSC after 72 h of cool storage. Our previous laboratorial study substantiated our clinical validation, considering evaluation of graft quality in different storage times and conditions; we have previously validated the best conditions for maintenance of PBSC in refrigerated storage.…”

“…There is no standard storage time for refrigerated PBSC in studies with fresh autologous transplantation of MM, ranging from 24 to 144 h 3,18–20 . Most studies comparing fresh and cryopreserved infusion have maintained fresh cells up to 48 h 3,4,11 and the increase of storage time must be clinically validated 10 . In our study, all fresh transplanted patients received PBSC after 72 h of cool storage.…”

“…4,5 Many factors can contribute to the negative effects of cryopreserved cells, such as the clinical symptoms of DMSO exposure (nausea, vomiting, abdominal cramps, headaches, 6 hypo or hypertension, bradycardia, hemolysis, rashes, renal failure, pulmonary edema, bronchospasm, cardiac arrest, and neurological damage [7][8][9] ), cell debris, cell aggregation, red blood cell lysis products, electrolyte imbalance, and the requirement of adjustable CD34+ collection goals, considering the cellular losses due to the cryopreservation/thawing process. Because of the benefits of fresh infusion and the lack of studies comparing clinical outcomes of fresh and cryopreserved stem cells transplantation, 10 we propose to compare the outcomes and adverse effects of transplanted patients under fresh and cryopreserved PBSC grafts.…”