Allogeneic Transplantation in Multiple Myeloma—Does It Still Have a Place?

Abstract

<jats:p>Novel drugs have improved survival for patients with multiple myeloma in recent years. However, the disease is still fatal. Allogeneic stem cell transplantation (Allo) has proven to cure some patients with the disease, but its role is controversial due to relatively high transplant-related toxicity and mortality (nonrelapse mortality, NRM). Using nonmyeloablative reduced-intensity conditioning (RIC), both toxicity and NRM can be reduced, and RICAllo is, therefore, an option for subgroups of patients. Upfront tandem autologous/RICAllo (Auto/RICAllo) was shown to be superior to single Auto or tandem Auto/Auto in both progression-free (PFS) and overall survival (OS) in two prospective studies with long-term follow-up, while three similarly designed studies did not detect a difference. A recent update of pooled patient data from four of these studies showed significantly superior PFS and OS with Auto/RICAllo. Importantly, none of these studies showed inferior results with Auto/RICAllo in patients less than 70 years of age. Auto/RICAllo appears to overcome some poor risk cytogenetic markers. Encouraging results have also been seen in treatment of relapsed patients. Combining Allo with new proteasome inhibitors and immunomodulatory drugs may further improve results. Other encouraging new cell therapies such as with CAR T-cells, NK- and CAR NK-cells may well have a place in combination with RICAllo. Such studies are warranted.</jats:p>

Improved survival in multiple Myeloma patients undergoing autologous stem cell transplantation is entirely in the standard cytogenetic risk groups

“…Due to the poor outcome in HR patients with ASCT, irrespective of additional novel drug treatment, allogeneic transplantation has been used with some success both by EBMT 26 and the BMT CTN 0102 27 and as well by Knop et al 28 in the setting of comparing tandem ASCT and reduced‐intensity conditioning allogeneic transplantation ( Auto/RICallo) to tandem autologous stem cell transplantation (Auto/Auto). Although allogeneic transplantation has a well‐established advantageous graft‐vs‐myeloma (GvM) effect, 29,30 it also is the cause of graft‐vs‐host disease (GVHD), mainly responsible for a death rate of about 10% in upfront transplants. Therefore, RICallo is still controversial.…”

Boosting Immunity against Multiple Myeloma

“…Nonmyeloablative reduced-intensity conditioning (RIC) aims at minimizing TRM and toxicity, relying more on exploring GVM for anti-myeloma efficacy. A recent manuscript published by Gahrton et al critically reviews the good results of RIC AlloSCT and how it could be combined with proteasome inhibitors, immunomodulators, monoclonal antibodies (mAbs) and cellular immune therapies [ 26 ]. The strategy of conducting RIC AlloSCT after ASCT (Auto/RICAlloSCT) aiming at debulking with the initial autologous and using the tandem RICAllo to generate GVM effect has been followed by several groups with good results.…”

Donor Lymphocyte Infusion to Enhance the Graft-versus-Myeloma Effect

“…However, the application of alloSCT is increasingly challenged by new therapies and its inherent association with treatmentassociated morbidity and mortality [3,4]. Therefore, the proper incorporation of alloSCT within a whole (immune-) therapeutic environment, which improves outcome of specific subgroups of patients, needs yet to be identified, especially in the advent of ever-improving outcomes using novel agents [5][6][7].…”