Long-term survival and polyclonal immunoglobulin reconstitution after allogeneic stem cell transplantation in multiple myeloma

Abstract

Despite significant progress made in the treatment of patients with multiple myeloma (MM) in the last decade, for patients with early relapse or rapidly progressing high-risk disease, allogeneic hematopoietic stem cell transplantation (SCT) might be an option leading to long-term survival. Here, we retrospectively analyzed the outcomes of 90 MM patients who received allogeneic SCT in our center between 1999 and 2017. We specifically assessed the association of impaired humoral immune reconstitution, referred to as immunoparesis, and post-transplant survival. Sixty-four patients received allogeneic SCT in relapse following 2-7 lines of therapy; 26 patients received upfront tandem autologous-allogeneic SCT. With a median follow-up of 76 months, OS and PFS were 52.6% (95% CI 42.9-64.3) and 36.4% (95% CI 27.6-47.9) at 2 years and 38.6% (95% CI 29.2-51.1) and 25.3% (95% CI 17.5-36.4) at 5 years, respectively. Receiving more than two therapy lines prior to transplantation was an independent risk factor for OS (HR 3.68, 95% CI 2.02-6.70) and PFS (HR 3.69, 95% CI 2.09-6.50). In a landmark analysis at day 200, prolonged immunoparesis was associated with reduced OS (HR 3.22, 95% CI 1.14-9.11). Allogeneic stem cell transplantation offers an additional treatment element that may lead to long-term remission in selected patients with poor prognosis, probably exploiting graft-versus-myeloma effects. Immunoparesis could potentially serve as an indicator for impaired survival following allogeneic transplantation, an observation to be further studied prospectively.

The Role of Allogeneic Stem Cell Transplantation in Multiple Myeloma: A Systematic Review of the Literature

“…Nevertheless, new drug therapies are constantly evolving the landscape of treatment: the study by Van Elssen et al describes haplo-BMT in MM may be a possible platform for future immunotherapeutic strategies utilizing the KIR-ligand mismatch; however, not necessarily with post-transplantation cyclophosphamide [ 25 ]. Immunoparesis was assessed by Eisfeld et al in the context of post-transplant survival, in that it may aid as a gauge for post-allogeneic transplantation mortality [ 27 ]. Graft-versus-host disease (GVHD) and infection were the main causes of non-relapse mortality in this group, which speculatively may have resulted from myeloablative conditioning with busulfan and cyclophosphamide [ 27 ].…”

“…Immunoparesis was assessed by Eisfeld et al in the context of post-transplant survival, in that it may aid as a gauge for post-allogeneic transplantation mortality [ 27 ]. Graft-versus-host disease (GVHD) and infection were the main causes of non-relapse mortality in this group, which speculatively may have resulted from myeloablative conditioning with busulfan and cyclophosphamide [ 27 ]. Similarly, the vincristine-Adriamycin-dexamethasone protocol in the Giaccone et al study enhanced the non-relapse outcomes of allogeneic recipients [ 36 ].…”

“…While the mechanism of action is not fully understood, it is speculated that the increase in Treg cells by RGI-2001 is via activation of invariant natural killer T (iNKT) cells [ 39 ]. Patients with greater than 9% CD4+ Treg cells have a greatly reduced risk of acute GVHD, and as a result, this could contribute to the prolonged overall survival of MM patients post-transplant [ 27 , 39 ].…”

“…Genetically defined high-risk MM in a subset of young patients with 17p deletions may experience limited remissions despite consistent therapeutic intervention [ 27 ]. Several studies discuss high-risk cytogenetics and the prognostic impact of allo-SCT on long-term survival [ 27 ].…”

“…Genetically defined high-risk MM in a subset of young patients with 17p deletions may experience limited remissions despite consistent therapeutic intervention [ 27 ]. Several studies discuss high-risk cytogenetics and the prognostic impact of allo-SCT on long-term survival [ 27 ]. The study by Eisfeld et al strengthens that delays in transplantation for patients with refractory disease results in poorer outcomes, while a careful selection of high-risk patients who are in earlier phases of disease benefit from allo-SCT while monitoring polyclonal immunoglobulins at least one year post-allo-SCT may identify mortality or relapse threats [ 27 ].…”