Elderly Multiple Myeloma (MM) Patients (≥70 years) Can Safely Undergo Autologous Stem Cell Transplantation (ASCT) but Have Shorter Overall Survival Than Younger Patients (<70 years).
Authors: Borgono Carla , Trieu Young , Xu Wei , Reece Donna E. , Trudel Suzanne , Kukreti Vishal , Anglin Peter , Chen Christine 
Published: October 2019

Abstract
Abstract 3409
Poster Board III-297

Introduction:
MM is a disease of the elderly with a median age at diagnosis of 65 years. For younger patients (<65 years), melphalan-based ASCT is standard therapy. However, limited data are available on the efficacy of ASCT in elderly patients (pts) over age 70, with concerns of excess toxicity and transplant-related mortality (TRM).

Methods:
From October 2000-August 2006, 548 MM pts were transplanted at our institution, 33 of whom (6%) were ≥70 years in age. Baseline demographics, disease characteristics, transplant and survival outcomes, including toxicities were collected retrospectively on all 548 patients and differences between the older patients (≥70 years) vs the younger pts (<70 years) were analyzed. Patients receiving a second salvage or tandem transplant were excluded. As per institutional transplant standard, all patients received 3-6 cycles of high-dose dexamethasone (DEX)-based induction therapy, underwent peripheral blood stem cell mobilization with cyclophosphamide 2.5g/m2 and GCSF 10mg/kg/day, and received melphalan 200mg/m2 for conditioning (no routine dose reductions for age). Ciprofloxacin prophylaxis and GCSF use (from day 7) were used routinely during the transplant process.

Results:
A total of 548 MM pts were studied: 33 pts ≥70 yrs of age (median 71 yrs; range 70-74); 515 pts <70 years of age (median 59 yrs; range 29-69).

Patient and disease characteristics:
MM subtypes for all pts included: IgG (59%), IgA (19%), biphenotypic (2%), IgD and IgM (<1%), light chain only (5%), other (10%) (no differences between the 2 groups). For the ≥70 yrs pts at baseline: median Hb was 98g/L (range 73-141), 22% of pts were hypercalcemic at diagnosis (median 2.38 mmol/L; range 2.09-4.24), 48% had significant renal dysfunction with serum creatinine >177 umol/L at diagnosis (median creatinine 94 umol/L; range 60-450), and 79% had elevated serum beta-2 microglobulin at diagnosis (median 269 nmol/L, range 5.8-505). No differences in baseline lab values were noted between the elderly and younger groups. Comorbid disorders in the elderly pts were common: 36% cardiac conditions (hypertension, coronary artery disease, heart failure, arrthythmias), 18% prior or pre-existing malignancy (solid tumours, lymphoma, leukemia), 12% diabetes, 12% gastrointestinal (ulcers, diverticular disease, colitis), 21% prior major infection (sepsis, pneumonia, TB), 6% renal disease (chronic renal failure, cystic disease), 6% CNS (stroke, seizures). Both renal disease and prior major infections were more common in the ≥70 group (renal 6 vs 1%, p=0.04 and infections 21 vs 5%, p=0.0003.

Transplant outcomes:
Although a standard stem cell mobilizing procedure was utilized for all pts, fewer stem cells (CD34+ cells) were collected in the ≥70 age group in comparison to the younger pts (median 12.3 vs. 9.1 × 106/kg; p=0.004). This did not, however, translate into significant differences in days to neutrophil or platelet engraftment, nor in days of hospitalization. For the ≥70 group, 76% achieved a PR (9% VGPR/CR) as assessed 3 months post-transplant, similar to the <70 group (p=0.08). Median progression-free survival from transplant was similar between groups (23.7 vs 21.8 mos, p=0.65) but median overall survival of the elderly pts was significantly shorter than that of younger patients (46.3 vs 80.4 mos, p = 0.03). Causes of death are unknown.

Toxicities:
Older patients exhibited cardiac toxicities (primarily arrhythmias) more frequently than younger patients during the transplant period (grade 1/2 - 3% vs 6%, grade 3/4 – 0 vs. 2%; p<0.0001). Treatment-related deaths, however, were uncommon in both groups [none in ≥70 pts vs 1.3% in <70 pts (p=0.27)].

Conclusions:

Disclosures:
Reece: Ortho Biotech: Honoraria, Research Funding.