Mortality from multiple myeloma within one year following autologous stem cell transplantation: defining an ultra high-risk population

Abstract Despite improvements in therapy, approximately 5% of patients who undergo autologous stem cell transplantation (ASCT) experience early mortality (EM), death within one year of transplant (EM-Post ASCT). Such patients tend to have few comorbidities suggesting their EM is due to aggressive underlying disease. We sought to characterize this ultra-high risk population through a retrospective review of patients with newly diagnosed MM treated with first line ASCT. Patients who died within one year of ASCT were matched for age, gender and year of transplant in a 1:2 fashion with a control group. Of 962 transplants performed between January 1st 2007 and May 1st 2019, 41 patients (4.3%) died within one year of ASCT from MM related causes. In a multivariate analysis, anemia, hypercalcemia, high risk cytogenetics and elevated LDH were associated with EM-Post ASCT. Forty patients (97.6%) received at least one novel agent. Most EM post-ASCT patients received second line chemotherapy (80.5%) though survival from initiation of second line chemotherapy was only 2.1 months. The primary reason for not receiving second line therapy was rapid relapse. Clinical parameters reflecting disease burden as well as high risk cytogenetics are associated with EM-Post ASCT. These patients have a dismal overall survival despite significant advances in treatment of patients with relapsed or refractory myeloma. Further study of these ultra high-risk patients is required to improve disease management and may give further insights into the biology of relapse and resistance in myeloma.