Allogeneic Transplantation for Multiple Myeloma – the Swiss Experience
Authors: Gerull Sabine , Chalandon Yves , Manz Markus G , Mohty Bilal , Schanz Urs , Stern Martin , Stussi Georg , Passweg Jakob R. 
Published: October 2019

Abstract
Abstract 3112
While the introduction of novel drugs has significantly improved the prognosis of multiple myeloma, cure remains rare. Allogeneic hematopoietic stem cell transplantation (HSCT) has been shown to induce long-term remission, but controlled studies have shown conflicting results and the role of allogeneic HSCT remains unclear. While in trials showing a survival advantage of allogeneic HSCT, the procedure was performed upfront as part of first-line therapy, in daily practice this modality is mainly used in patients with primary refractory disease, in patients with high-risk features or after multiple relapses.
To assess the effect of allogeneic HSCT, we performed a retrospective analysis of patients with multiple myeloma who received an allogeneic HSCT in Switzerland. At the time of writing, outcome data was available from 2 of the 3 national transplant centers. In these 2 centers, 76 allogeneic transplants were performed in 74 patients between 1991 and 2010 at a median of 21 (range 2–156) months after diagnosis. Of these, 41% (n=31) were performed upfront as part of first line therapy, while 59% (n=45) were performed after one or more relapses, or for refractory disease. Patients had received a median of 2 (range 0–7) lines of therapy and 1 (range 0–3) autologous transplant before allogeneic HSCT. Before transplant, 67% (n=51) of patients had reached at least a partial remission, 13% (n=10) were in complete remission.
The median age at transplant was 52 (range 32–68) years. Conditioning was myeloablative in 24% (n=18), and non-myeloablative in 76% (n=58). 66% (n=50) had a related sibling donor, while 34% (n=25) had an unrelated donor and one patient received a cord blood graft. The majority of patients (n=68) received peripheral stem cells. In 3 patients, the graft was T-cell depleted.
53% (n=40) of patients experienced acute graft-versus-host disease (GvHD) grade II-IV, 16% (n=12) had grade III-IV. Chronic GvHD occurred in 49% (n=37) of the 67 of patients surviving beyond day 100, extensive in 30 patients. 14 patients received donor lymphocyte infusion (DLI) either due to progressive disease (n=11) or per protocol following T-cell depleted transplant (n=3).
At the time of analysis, 37 patients are alive, with a median follow up of survivors of 3.9 years. While 23 deaths were caused by the underlying disease, the cumulative incidence of transplant related mortality at 2 years post-transplant was 17% (95% CI: 8%-26%).
Following transplant 43% (n=33) of patients reached a complete remission, 13% (n=10) attained a partial remission and 18% (n=14) a very good partial remission. The median progression free survival (PFS) was 343 days, with a 2 and 5 year PFS of 40% (95% CI: 29%-51%) and 34% (95% CI: 22%-46%), respectively. Median overall survival (OS) was 3.4 years, with a 2 and 5 year OS of 57% (95% CI: 36%-68%) and 46% (95% CI: 34%-58%) respectively.
When comparing patients who received a planned allogeneic transplantation upfront rather than later in the disease course, the former had a significantly better 2 year OS and PFS: 77% versus 43% (p<0.001) and 57% versus 28% (p=0.022) respectively (Figure 1). Patients in partial remission or better at the time of transplant also had a superior 2 year PFS (49% versus 24%, p=0.04), with no significant difference in OS. Patients who developed chronic GvHD had an improved OS (HR 0.65, 95% CI 0.29–1.44) and PFS (HR 0.77, 95% CI 0.34–1.71), however this did not reach statistical significance. Finally, while PFS was not influenced by type of donor, we observed an improved 2 year OS for patients with a related donor (64% versus 45%, p=0.02).
While long term remission following allogeneic HSCT can be achieved in a subset of patients, morbidity and mortality remain substantial. Clinical benefit is highest when used early in the disease course. Clinical studies evaluating the benefit of allogeneic HSCT as part of salvage strategies are needed.

Disclosures:
No relevant conflicts of interest to declare.