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

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

Sorafenib maintenance after allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia with FLT3–Internal tandem duplication mutation (SORMAIN)

PURPOSE Despite undergoing allogeneic hematopoietic stem cell transplantation (HCT), patients with acute myeloid leukemia (AML) with internal tandem duplication mutation in the FMS-like tyrosine kinase 3 gene (FLT3-ITD) have a poor prognosis, frequently relapse, and die as a result of AML. It is currently unknown whether a maintenance therapy using FLT3 inhibitors, such as the multitargeted tyrosine kinase inhibitor sorafenib, improves outcome after HCT.PATIENTS AND METHODSIn a randomized, placebo-controlled, double-blind phase II trial (SORMAIN; German Clinical Trials Register: DRKS00000591), 83 adult patients with FLT3-ITD-positive AML in complete hematologic remission after HCT were randomly assigned to receive for 24 months either the multitargeted and FLT3-kinase inhibitor sorafenib (n = 43) or placebo (n = 40 placebo). Relapse-free survival (RFS) was the primary endpoint of this trial. Relapse was defined as relapse or death, whatever occurred first.RESULTS With a median follow-up of 41.8 months, the hazard ratio (HR) for relapse or death in the sorafenib group versus placebo group was 0.39 (95% CI, 0.18 to 0.85; log-rank P = .013). The 24-month RFS probability was 53.3% (95% CI, 0.36 to 0.68) with placebo versus 85.0% (95% CI, 0.70 to 0.93) with sorafenib (HR, 0.256; 95% CI, 0.10 to 0.65; log-rank P = .002). Exploratory data show that patients with undetectable minimal residual disease (MRD) before HCT and those with detectable MRD after HCT derive the strongest benefit from sorafenib.CONCLUSION Sorafenib maintenance therapy reduces the risk of relapse and death after HCT for FLT3-ITD-positive AML