Efficacy and Safety of Autologus Hematopoietic Cell Transplantation in Elderly Patients with Multiple Myeloma: A Retrospective Israeli Multi-Site Cohort Study
Authors: Cohen Yael C , Zuckerman Tsila , Yeshurun Moshe , Perez Galit , Magen Hila , Henig Israel , Levi Itai , Shargian Liat , Trestman Svetlana , Rouvio Uri , Naparstek Elizabeth , Ganon-Elazar Eti , Avivi Irit , Ram Ron 
Published: October 2019

Abstract
Background: High-dose therapy (HDT) with melphalan 200 mg/m2 (MEL200) followed by autologous hematopoietic cell transplantation (HCT) after an induction therapy is considered the standard of care for patients with newly diagnosed multiple myeloma younger than 65 years. Data are limited for patients above the age of 65 years. We aimed to test the feasibility, efficacy and toxicity of HDT/HCT in patients > 65 years.
Methods: We included all consecutive patients with multiple myeloma aged 60 and above who underwent an upfront first HCT within 9 months of diagnosis, at 4 Israeli bone marrow transplantation centers. We recorded and compared transplantation-associated toxicity and outcomes between patients >65 years (elderly group) and patients 60-65 years (younger group).
Results: 220 patients fulfilling the above inclusion criteria underwent HCT between the years 2000 – 2014. Median age of the younger and the elderly group were 62 (range, 60-65) and 68 (range, 66-75), respectively. There were no differences in patient characteristics between the 2 cohorts except of the status of disease at HCT, Table. As expected, higher percentage of patients in the younger group received melphalan 200 mg/m^2 compared to the older group (77% vs. 57%, p=.002). There were no differences in the median day of neutrophil engraftment, the incidence of documented infections, the percentage of patients with grade 3-4 mucositis and the occurrence of cardiovascular events, between the two groups. Within a median follow up of 18 months, 136 patients are alive. There was no difference in non-relapse mortality at 100 days post HCT (4.7%, vs. 5%, p=.9). There was no difference in the percentage of patients with improvement in disease status after HCT, per the IMWG criteria, between the 2 groups in all patients (36%, vs. 35%, p=.87) and among sub-group of patients who failed to reach VGPR pre-transplant (p=.18). At 3 year post HCT progression-free survival was higher in the younger group, compared to patients in the elderly group (42% vs. 29% , p=.04), however this was no longer true after adjustment for disease status prior to HCT (p=.49). In the elderly group, melphalan 200 mg/m^2 compared to lower doses were not associated with improved progression-free survival (p=.69), Figure. Multivariate analysis identified only lambda chain myeloma and no improvement in disease response after HCT to predict a worse progression-free survival (HR 1.7, p=.045 and HR=2.9, p=.021, respectively), while melphalan doses and the age of patients did not predict progression-free survival. There was no difference in overall survival between the younger and the elderly groups (p=.2).
Conclusions: Toxicity profile, response rate, progression-free and overall survival of HCT in elderly patients with myeloma is similar to younger patients. Lower melphalan doses given as a preparative regimen do not hamper efficacy of HCT. Randomized controlled trials are needed to confirm the feasibility and outcomes of HCT in patients older than 65 years.
Table Patients’, collection and preparative regimen’s characteristics Datum Young group (N=133) Older group (N=87) P value Age (median, range) years 62 (60-65) 68 (66-75) <.001 Female (%) 47 46 1 ISS 2-3 (%) 54 45 .65 Novel-agents-based induction (%) 86 78 .18 > 1 line prior to HCT 76 70 .41 Status prior to auto >PR (%) 68 54 .08 Collection at steady state (%) 44 35 .32 Pleriixafor (%) 6 6 1 Total collected cells (median, range) CD34/kg 6.85 (1.9-33.6) 6.25 (2.6-20) .06 MEL 200 (%) 77 57 .002
Figure 1 Figure 1.

Disclosures
No relevant conflicts of interest to declare.