Chapter 3 – Treatment of transplant-eligible patients

Contributors: Mohamad Mohty, Florent Malard, Jean-Luc Harousseau

5 – Allogeneic transplantation

The existence of a graft-versus-myeloma (GVM) effect is well established. The best illustration of GVM effect is probably the achievement of remission after donor lymphocyte infusion (DLI) in patients with persistent disease or relapse after allo-SCT [46]. Furthermore, it had been shown in a patient with MM who received an allogeneic transplant and DLI with minor histocompatibility antigens mismatch, that achievement of CR was accompanied by the emergence of cytotoxic T cells directed against some minor histocompatibility antigens expressed on MM cells [47]. Despite the well-established GVM effect, the role of allo-SCT in MM is controversial because of the high morbidity and mortality rates while studies presented conflicting results. Thus, in the setting of a standard myeloablative conditioning (MAC) regimen, non-relapse mortality (NRM) can range from 30% in more recent studies to 49% in older studies [48], and evidence of survival benefit are lacking, precluding its use. Reduced intensity conditioning (RIC) regimens were developed with the aim to decrease NRM in elderly patients, in heavily pretreated patients, or in those with medical comorbidities precluding the use of a standard MAC regimen.

Several prospective randomized studies compared auto-SCT versus tandem auto-SCT/RIC allo-SCT in MM. Despite some studies demonstrating an advantage in OS, PFS, and relapse in favor of tandem auto-SCT/RIC allo-SCT [49], others studies failed to demonstrate an advantage [50]. Furthermore, in these studies no patient received the new standard for MM frontline treatment based on a new agent for combination induction and auto-SCT. Consequently, it is impossible to draw a conclusion on those results regarding the use of tandem auto-SCT/RIC with allo-SCT in front-line treatment. Although, allo-SCT in the first-line setting should still be considered as investigational, it may be considered for young patients with high-risk disease who are willing to accept a high NRM, and the unproven nature of this therapy, for a chance of better long-term survival.

At relapse, the feasibility of allo-SCT with a reduced intensity conditioning has been demonstrated in several studies [51–53]. However, despite the use of RIC, NRM remains high at around 20–25% at 1 year and relapse incidence remain high, leading to a PFS at 2 years of 26–38% [51–53]. Furthermore, the high incidence of graft-versus-host disease significantly contributes to NRM and could impair the quality of life in surviving patients. Overall, allogeneic transplantation cannot be routinely recommended outside clinical trials given the high risk of non-relapse-related morbidity and mortality, it may be an option in few selected patients, particularly those with high-risk disease.