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).

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).

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.

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).

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.

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.

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)].

1. Our data supports the feasibility and safety of ASCT in elderly MM pts (≥70 years). In our elderly cohort, non-fatal cardiac toxicities were more common than in younger pts but no early transplant deaths were noted.

2. Contrary to common perception, elderly MM pts undergoing transplant do not appear to have significantly higher rates of pre-existing comorbidities, likely reflecting an appropriately stringent selection process.

3. Although ASCT is feasible in MM pts ≥70 years, overall survival is shorter than in younger pts. Whether this is simply related to natural senescence or to disease/treatment complications remains unclear.

4. At our institution, in the absence of a clear standard of care for MM pts over age 65, we continue to offer ASCT to selected, fit, elderly pts.

Reece:Ortho Biotech: Honoraria, Research Funding.