The Graft-Versus-Myeloma Effect: Chronic Graft-Versus-Host Disease but Not Acute Graft-Versus-Host Disease Prolongs Survival in Patients with Multiple Myeloma Receiving Allogeneic Transplantation

Abstract

We conducted a study of patients with multiple myeloma (MM) undergoing allogeneic transplantation to evaluate outcome parameters. Fifty-seven consecutive patients with MM received an allogeneic transplantation between 2004 and 2011 at our institution. Patients who had received at least 1 prior autologous transplantation were included. Twenty-six patients underwent allogeneic transplantation for consolidation after a response to their first autograft, and 30 patients received an allogeneic transplantation as salvage therapy. Donor source was evenly distributed between related and unrelated. The median follow-up was 52 months. Thirty-two (57.1%) patients achieved a complete response (CR). At 5 years, 49.2% of all patients were in CR. Sixteen patients received either donor lymphocyte infusions or immune suppression withdrawal for disease progression, with a 62.5% response rate. The 5-year overall survival (OS) for all patients was 59%. The 5-year OS for the 30 patients in the consolidation group was 82% compared with 38% for those in the salvage group. In multivariate analysis, 3 factors remained significantly associated with OS. These include being in the salvage group (hazard ratio [HR], 4.05; P = .0196), acute graft-versus-host disease (aGVHD) (HR, 2.99; P = .034), and chronic graft-versus-host disease (cGVHD), which was highly protective, with a 5-year OS of 78.8% for patients with cGVHD versus 42.6% for patients without cGVHD (HR .17, P = .008). Our data show that allogeneic transplantation for MM can lead to sustained remissions. aGVHD is significantly deleterious to OS and progression-free survival, whereas cGVHD is strongly favorable, supporting an important role for the graft-versus-myeloma effect.

Favorable long-term outcome of patients with multiple myeloma using a frontline tandem approach with autologous and non-myeloablative allogeneic transplantation

“…In this study, we also aimed to take advantage of the possible protective effect of chronic GvHD on MM relapse. 11,12 Our results challenge the commonly accepted belief that allogeneic HSCT is overly toxic and associated with prohibitive NRM. Despite complete discontinuation of preventive immunosuppression by day +100, we observed a very low incidence of grades II-IV acute GvHD.…”

“…It is well recognized that grades II-IV acute GvHD is associated with deleterious outcome and lower PFS and OS. 12,18,20,35,39 Conversely, the favorable impact of chronic GvHD on relapse is another important result. We speculate that the higher incidence of chronic GvHD observed in our cohort directly correlates with a GvMM effect and possibly explains the impressive PFS observed in our study.…”

“…[7][8][9] Factors associated with improved PFS included fewer treatments before transplant, grade I acute GvHD and presence of chronic GvHD. This protective effect of chronic GvHD, [10][11][12][13][14] response after donor lymphocyte infusion 15,16 and the discovery of antibodies against highly expressed myeloma-associated Ags 17 following allogeneic transplant are additional clinical observations supporting the existence of a graft-versus-myeloma (GvMM) effect.…”

Allogeneic stem cell transplantation for multiple myeloma: is there a future?

“…46 The prospective BMT CTN 0102 study and a retrospective CIBMTR study also found that the occurrence of cGVHD after allo-SCT correlated with freedom from progressive MM. 33,47 Other single institution studies have also shown that development of cGVHD is significantly associated with better OS, 37,48 further substantiating the GVM effect. Additionally, in vitro or in vivo T-cell depletion has been associated with higher relapse rates and a need for subsequent DLI after allotransplant.…”

“…36 In another single institution study, development of cGVHD was associated with favorable OS and PFS further substantiating the importance of GVM effect. 37 Allogeneic transplantation in multiple myeloma B Dhakal et al…”