Influence of Age on Survival after a Tandem Hematopoietic Stem Cell Transplantation Procedure in Patients with Multiple Myeloma: Results of the Prospective GEM-2000 Protocol.
Authors: Sureda A. , Blade J. , Lahuerta J.J. , de la Rubia J. , Martinez R. , Carrera D. , Garcia-Laraña J. , Alegre A. , Hernandez M. , Rivas C. , Ribera J.M. , Peñarrubia M.J. , Palomera L. , Prosper F. , de Arriba F. , Leon A. , Abella E. , Hernandez-Ruiz B. , Casado F. , Garcia-Ruiz J.C. , Besalduch J. , Fernandez-Calvo F.J. , Touchard A. , Miguel J. San ,   for the Spanish Group of Multiple Myeloma (MM)
Published: October 2019

Abstract
We have analysed the influence of age on survival after a tandem hematopoietic stem cell transplantation prospective protocol (GEM-2000) in patients diagnosed of multiple myeloma (MM). From 870 patients with symptomatic MM aged < 70 years and prospectively included in the GEM-2000 protocol, we have analysed the outcome of a group of 637 patients [351 males, median age of 59 (range, 32 – 70) years] and treated with at least one autologous stem cell transplantation (ASCT). Sixteen patients (2.5%) were between 31 and 40 years of age (group A), 96 patients (15%) between 41 and 50 years (group B), 244 patients (38%) between 51 and 60 years (group C) and the remaining 281 patients (44.5%), between 61 and 70 years (group D). In 325 patients the M component at diagnosis was an IgG (51%). Fifty three patients (8%) had stage I at diagnosis, 232 patients (37%) stage II and 352 patients (55%), stage III. One hundred and one patients (16%) presented with renal insufficiency at diagnosis. Significantly lower levels of serum albumin at diagnosis were observed in the older group of patients (3.88 g/L vs 4.46 g/L, p = 0.05). Most of the patients (612, 96%) were initially treated with the alternating protocol VBCMP/VBAD. The response rate to the first line therapy was of 84% (n = 533), without differences between group D and the rest of the groups. The BUMEL protocol (busulfan 10 mg/kg po plus melphalan 140 mg/m2 iv) and MEL200 (melphalan 200 mg/m2 iv) were the two conditioning regimens used for the first intensive procedure. Although the proportion of older patients (group D) who received MEL200 was higher than in the younger groups of patients (groups A – C) (35% vs 44%), these differences did not reach a statistical significance. At three months after the first ASCT, 30% of the patients had reached a complete remission with negative immunofixation (CR IF-); this percentage was significantly superior in the younger group of patients (groups A – C) with respect to group D (32% vs 27%, p = 0.02). Transplant related mortality (TRM) was also significantly superior in group D (8% vs 3%, p = 0.01). At the time of follow-up, 124 patients (19%) have received a second transplantation; a second intensive procedure was more frequently performed in the younger group with respect to group D (25% vs 12%, p = 0.0001). This second transplant was an ASCT in 73% of the patients (65% in groups A – C vs 94% in group D, p = 0.04). With a median follow-up of 24 months, 508 patients are alive. Actuarial 2-year overall survival (OS) and event free survival (EFS) for the whole population of patients are 75%±2% and 57%±2%, respectively, with statistically significant differences between groups A - C and group D (77%±3% vs 72%±3%, p = 0.05 and 62%±3% vs 52%±4%, p = 0.02, respectively). The overall benefit of the intensification procedure seems to be less in the older group of MM patients (61 – 70 years) included in the GEM-2000 protocol. These results could be related to the achievement of a significant lower rate of CR IF- after the first ASCT and a higher TRM in this older population of patients.