Induction therapy prior to autologous stem cell transplantation (ASCT) in newly diagnosed multiple myeloma: an update

Abstract

The current standard of care model for newly diagnosed fit multiple myeloma (NDMM) patients is the sequential treatment of induction, high dose melphalan, autologous stem cell transplantation (ASCT), and maintenance. Adequate induction is required to achieve good disease control and induce deep response rates while minimizing toxicity as a bridge to transplant. Doublet induction regimens have greatly fallen out of favor, with current international guidelines favoring triplet or quadruplet induction regimens built around the backbone of the proteasome inhibitor bortezomib and dexamethasone (Vd). In fact, the updated 2021 European Haematology Association (EHA) and European Society for Medical Oncology (ESMO) clinical practice guidelines recommend the use of either lenalidomide-Vd (VRd), or daratumumab-thalidomide-Vd (Dara-VTd) as first-line options for transplant-eligible NDMM patients, and when not available, thalidomide-Vd (VTd) or cyclophosphamide-Vd (VCd) as acceptable alternatives. Quadruplet regimens featuring anti-CD38 monoclonal antibodies are extremely promising and remain heavily investigated, as is the incorporation of more recent proteasome inhibitors such as carfilzomib. This review will focus on induction therapies prior to ASCT examining the latest data and guidelines on triplet and quadruplet regimens.

Delayed diagnosis resulting in increased disease burden in multiple myeloma: the legacy of the COVID-19 pandemic

“…In the UK, aiming to reduce hospital footfall, therapy delivery underwent a significant change, with an increase in doublet induction regimens, a preference for oral-based treatment strategies and a reduction in the rates of autografting [31], some of which may have been related to planned autograft deferrals. The current body of evidence serves to illustrate the impact of triplet, and more recently quadruplet induction regimens, followed by stem cell transplant consolidation to maximize depth and durability of response, as well as survivorship [32][33][34]. It is therefore anticipated that pandemic will leave a mark on myeloma survival in the years to come.…”

An Update on Hematopoietic Stem Cell Transplantation in Patients with Multiple Myeloma

“…Since the mid-1990s and despite the recent availability of several lines of novel agents, high-dose (HD) melphalan followed by autologous HSCT is still the standard of care for newly diagnosed patients with MM who are eligible for autologous HSCT [20][21][22][23]. The long-term outcome of patients with MM subjected to autologous HSCT has improved significantly over the last three decades [1,24].…”

Clonal haematopoiesis of indeterminate potential predicts delayed platelet engraftment after autologous stem cell transplantation for multiple myeloma

“…Dear Editor, Despite the introduction of several novel drugs, the current standard of care for transplant-eligible newly diagnosed multiple myeloma (NDMM) patients is still the sequential strategy of induction therapy, high dose melphalan (HDM), autologous stem cell transplantation (ASCT), and maintenance. 1,2 However, HDM-ASCT inevitably results in a period of bone marrow hypoplasia after transplantation, and delayed haematopoietic engraftment or engraftment failure further results in an increased risk of severe infection, haemorrhage, more prolonged hospitalization, increased resource utilization, and relapse. Although existing literature strongly supports the notion that the content of CD34 + cells in the graft is the single most important determinant of neutrophil and platelet reconstitution after myeloablative chemotherapy, some patients receiving a CD34 + cell dose widely considered adequate for transplantation suffer delayed haematopoietic engraftment.…”