Autologous Stem Cell Transplantation (auto-SCT) in Elderly Patients with Multiple Myeloma (MM): Age per se Does Not Affect Outcome.
Authors: El-Cheikh Jean , Kfoury Elias , Chabannon Christian , Stoppa Anne-Marie , Bouabdallah Reda , Coso Diane , de Collela Jean-Marc Schiano , Ivanov Vadim , Aurran Therese , Gastaut Jean-Albert , Blaise Didier , Mohty Mohamad 
Published: October 2019

Abstract
Auto-SCT for MM can provide superior outcome to standard treatments. Since its introduction, auto-SCT has usually been limited to MM patients aged up to 60–65 years. However, traditional upper age limits for auto-SCT are being currently challenged along with the definition of “elderly” itself, especially that no obvious differences in MM biology has been elucidated to justify an arbitrary cut-off of 65 years. This retrospective single centre analysis assessed the outcome of 186 consecutive MM patients aged over 60 years treated with auto-SCT, with the specific aim to compare the outcome of the 82 “elderly” (age>65 y.) patients subgroup, with their 104 “younger” mates aged between 60 and 65 years treated in the same period and in the same auto-SCT program. Median age among the total 186 patients population was 64 (range, 60–77). Except for age, both groups were comparable (P=NS) as for demographic features, disease characteristics (S&D stage, monoclonal component), and prognostic factors (b2-microglobulin). The majority of patients (91%) received homogeneous “induction” VAD chemotherapy, with this being comparable between the “elderly” (87%) and “younger” (94%) group. In this population, and prior to auto-SCT, the calculated hematopoietic cell transplantation-specific comorbidity index (adapted from the Charlson Comorbidity Index) was also comparable between both groups (77% of the “younger” patients with a 0–1 index, vs. 74% in the “elderly” group; P=NS). The peripheral blood stem cells mobilization procedures (G-CSF with or without chemotherapy) were also comparable between both groups. 97% of the patients received high-dose melphalan conditioning for auto-SCT. 33% of the “younger” and 28% of the “older” group (P=NS) completed a second auto-SCT. ANC and platelets recovery were comparable between both groups (P=NS), and the median length of hospitalization for the first auto-SCT was not different between the two groups: 19 (range, 2–32) days in the “younger” group vs. 17 (range, 2–39) in the “older” group; P=NS). Infectious and other “serious” auto-SCT-related complications were also comparable between groups (P=NS). With a median follow-up of 41 (range, 5–227) months after auto-SCT, 120 patients are still alive. Disease progression (n=40; 61%) was the main cause of death, with this being comparable between both groups. Auto-SCT-related mortality was 3.8% (n=4/104) in “younger” and 3.7% (n=3/82) among “older” subjects. Comparing “younger”/”older” subjects, progression-free survival was significantly higher in the younger group (P<10e-4). However, disease response rate after the first auto-SCT was comparable (CR, VGPR and PR rates: 88% vs. 90%, P=NS), and overall survival (OS) was also comparable (57% vs. 54% at 5 years, P=NS; 32% vs. 24% at 10 years, P=NS). In a Cox multivariate analysis model, none of the relevant characteristics was shown to be a critical prognostic features for OS. Of note, age was insignificant for both OS and transplant-related mortality. We conclude that there is no clear justification for an age-discriminant policy for MM therapy. “Physiologic” aging is likely more important than “chronologic” aging. Thus, all treatment options, including auto-SCT in the “elderly” population, must be rigorously evaluated, as age does not appear to be an adverse parameter for selected MM patients receiving high-dose melphalan therapy with peripheral blood stem cell support.