Allogeneic stem cell transplantation in multiple myeloma 

In April, two review articles were published in peer-reviewed journals, reflecting on the role of stem cell transplantation (SCT) in multiple myeloma (MM). The first review, published in Cancer and authored by Roberto Mina and our co-chair Sagar Lonial, questioned the role of SCT in MM.¹ The second review, in Blood Cancer Journal, by Rama Al Hamed, Adbul Hamid Bazarbachi and colleagues, including our Steering Committee member, Mohamad Mohty, reflected on the current status of autologous-SCT (ASCT) in MM.²

Here, the MM Hub present a series of three articles on the current status of SCT in MM and discuss its role in treatment both now, and in the future. This article focuses on allogeneic SCT (allo-SCT) and its role in the treatment of MM. The following articles will focus on ASCT in MM - the optimal regimens and the big questions. 

Background: allo-SCT¹

Allo-SCT, whereby a patient receives stem cells from a healthy donor, is postulated as being potentially curative in MM based on the graft-versus-myeloma effect. A study by Michele L Donato and colleagues showed allo-SCT could provide sustained remissions in a small cohort of 57 patients who had received one prior ASCT. In this study, chronic graft-versus-host disease (GvHD) had a favorable impact on OS and PFS indicating a graft-versus-myeloma effect.³

Allo-SCT in newly diagnosed MM (NDMM)¹

Metaanalysis data has failed to show a benefit of allo-SCT + ASCT to tandem ASCT in patients with NDMM:^4,5

• Patients treated with ASCT + allo-SCT reduced intensity conditioning (RIC) had higher complete response (CR) rates but also more frequent treatment-related mortality (TRM)
• Relapse remained an issue
• Tandem ASCT alone was superior in relation to PFS and OS

To maximize the graft-versus­-myeloma effect, trials comparing tandem ASCT/allo-SCT with RIC to tandem ASCT were designed. Only two of these showed a benefit in PFS and OS of tandem ASCT/allo-SCT with RIC, and these were limited by a lack of randomization and pre-dated the era of novel agent use. Subsequent trials have failed to replicate this benefit.

Table 1: Outcomes from trials comparing tandem ASCT to tandem ASCT/allo-SCT in patients with NDMM (tandem ASCT vs tandem ASCT/allo-SCT)^6-10

Conclusion: allo-SCT is not recommended as a standard of care for patients with NDMM. Young, fit patients with NDMM however may be considered for allo-SCT in the clinical trial setting.¹

Salvage allo-SCT in relapsed/refractory MM (RRMM)¹

 Limited data exists for allo-SCT in RRMM

• The European Society for Blood and Marrow Transplantation (EBMT) registry shows the use of allo-SCT has increased, and is becoming more common in later treatment lines¹⁰

Table 2: Outcomes of patients with RRMM undergoing allo-SCT^11-12

Conclusion: The advantage of allo-SCT over ASCT has not been proven so far and allo-SCT for RRMM is currently limited to a trial setting.

Allo-SCT in high-risk MM¹

Trials have been designed, retrospectively, to analyze the impact of allo-SCT on patient outcomes in the high-risk subgroup. However, these too have failed to show a benefit of allo-SCT over.

Table 3: Analyses of allo-SCT in high-risk MM^13-14

Conclusion: In a clinical trial setting, allo-SCT may be considered for young, fit patients with high risk NDMM, in-line with International Myeloma Working group recommendations, but is not routinely recommended.

Summary

The authors did not recommend allo-SCT as a standard of care in the NDMM setting, aside from in clinical trials, and it has no proven benefit over ASCT.