Background: Successful treatment of plasma cell myeloma (PCM) includes cytotoxic chemotherapy, high-dose chemotherapy with autologous stem cell transplant (ASCT), immunomodulatory drugs and proteasome inhibitors. Landmark papers by Kumar et al and Brenner et al in 2008, and Turesson et al in 2010, showed significant gains in median overall survival (OS) of PCM patients but these gains were attributed primarily to age < 65 years. Marginal improvement seen in older patients did not reach significance. We examined outcome for patients treated on frontline ECOG protocols over the past 33 yrs to assess whether there has been survival improvement in elderly patients. Methods: We reviewed 4 phase III study data for previously untreated PCM patients. ASCT regimens were excluded. OS was analyzed using Kaplan-Meier and group differences were tested using 2-tailed log-rank test. Cohorts were identified based on date of accrual to clinical trial: A 1988-1993, B 1994-2000, and C 2001-2006. Results: 1,528 patients were treated (Table). 727 (48%) were > 65 yr. 358 pts (23%) were age 70-79 yr and 48 pts (3%) were > 80 yr. For all pts, 5 yr probability of OS was significantly better in cohort C (51%) as compared to cohorts A (31%) and B (29%), respectively (p<0.0001). For pts > 65 yr, this effect on OS still was seen but substantially diminished (39% on C versus 26% on A and B, p=0.012), while in the younger cohort effect is more pronounced (63% on C, 35% on A and 32% on B). Conclusions: OS in elderly PCM pts has improved but OS gains still lag behind younger PCM pts. Increased comorbidity, treatment-related toxicity, physician/patient biases, and differences in disease biology in elderly patients are all possible contributing factors to worse outcomes. In-depth review of these variables may contribute to improved design of future clinical trials for elderly PCM pts.

* Comparing C to A+B, p≤.001 ** Comparing C to A+B, p=.012