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.
Highlights
The range of therapeutic options for patients with multiple myeloma (MM) increased substantially, for the majority of younger patients, the backbone of triple induction therapy, consolidation with high-dose melphalan, and autologous stem cell transplantation (SCT) followed by maintenance treatment leads to prolonged disease remission and remains the standard of care [1]
SCT, allogeneic stem cell transplantation; International Staging System (ISS), international staging system; PI, proteasome inhibitors; IMiD, immunomodulatory drugs; MRD, matched related donor; MUD, matched unrelated donor; graft-versus-host disease (GvHD), graftversus-host disease; CSA, cyclosporine A; MMF, mycophenolate mofetil; ATG, anti-thymocyte globulin; MTX, methotrexate reached (n.r.)) and 36.9 months, respectively
As the absolute lymphocyte count has been shown to be associated with survival after allogeneic SCT, we aimed to rule out that immunoglobulin levels were a surrogate for decreased lymphocyte count [13]
Summary
The range of therapeutic options for patients with multiple myeloma (MM) increased substantially, for the majority of younger patients, the backbone of triple induction therapy, consolidation with high-dose melphalan, and autologous stem cell transplantation (SCT) followed by maintenance treatment leads to prolonged disease remission and remains the standard of care [1]. The beneficial role of timely cellular immune reconstitution after allogeneic SCT on outcomes has been outlined. Immunoparesis, defined as suppression of polyclonal Ig uninvolved in the clonal disease, reflects a lower percentage of normal bone marrow plasma cells and is observed in most MM patients at diagnosis, being often reversible under treatment [14, 15]. Kinetics of polyclonal Ig reconstitution has not been systematically evaluated after allogeneic SCT
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