Outcomes of Previously Untreated Older Patients with Multiple Myeloma (MM) over Time: An Analysis of 3 Consecutive Trials Conducted by the NCIC CTG, 1983–2003.
Authors: Luk Cynthia , Ding Keyue , Belch Andrew R. , Browman George P. , Shustik Chaim , Djurfeldt Marina , Johnston Dianne , Shepherd Lois E. , Meyer Ralph M. 
Published: April 2020

Abstract
Background: Improved overall survival (OS) over time has been observed in large population databases assessing patients (pts) with MM. Recent interventions, such as routine use of bisphosphonates, and stem cell transplantation for younger pts may account for some of this improvement. It is unclear whether these improvements have been seen in older symptomatic pts. The purpose of this study is to assess outcomes over time of pts &gt; 65 yrs with MM who were entered on 3 consecutive randomized trials conducted by NCIC CTG.
Methods: Databases evaluated included MY4 (1983–84; N=173), which compared etidronate to placebo; MY6 (1987–92; N=402), which tested the role of maintenance interferon; and MY7 (1995–2003; N=584), which tested dexamethasone as induction and maintenance therapy. All pts had symptomatic Salmon-Durie stage I or stage II–III MM, were previously untreated, and received melphalan 9 mg/M2 and prednisone 100 mg daily x 4, Q4 weeks; 231 pts in MY7 received melphalan and dexamethasone according to random allocation. We performed uni- and multivariate analyses to compare outcomes of pts ≤ 65 and &gt; 65 yrs of age, to assess outcomes of pts &gt; 65 yrs over time, and to assess other prognostic determinants in pts &gt; 65 yrs. Outcomes of interest included OS, progression-free survival (PFS), myeloma-related survival (MRS), defined as time from registration or randomization until death from myeloma or treatment toxicity, and time from first progression to death (FPTD).
Results: All eligible pts were included. By multivariate analyses, patients &gt; 65 yrs had inferior OS (p=0.0003), FPTD (p=0.0006), and a trend for inferior MRS (p=0.08) in comparison with pts ≤ 65 yrs; no difference in PFS was detected. In comparing pts &gt;65 yrs on MY4, MY6 and MY7, important differences in the baseline characteristics of the patients of the 3 trials were noted; pts treated on MY6 received lower median cumulative doses of melphalan (356 mg/M2) than those entered on to MY4 (432 mg/M2) or MY-7 (464 mg/M2). Median unadjusted outcomes of these pts by trial are listed in the table below. By multivariate analysis, pts &gt; 65 yrs entered on to MY4 had a superior MRS in comparison with MY7 (p=0.037) and a trend to superior OS (p=0.053) and FPTD (p=0.06). No differences in PFS between trials were detected. Baseline characteristics associated with inferior OS in pts &gt; 65 yrs included ECOG PS &gt; 1 (p=0.0002), male gender (p=0.001), baseline Hb ≤ 85 g/L (p=0.001), and elevated baseline serum calcium (p=0.01).
Conclusions: Patients &gt; 65 yrs have inferior outcomes in comparison with younger pts. We were unable to detect improvements in outcomes of these pts over time.
Median unadjusted outcomes of pts age &gt; 65 yrs by trial MY4 (95% CI) MY6 (95% CI) MY7 (95% CI) OS (yrs) 2.38 (1.73–3.32) 2.75 (2.36–3.24) 2.53 (2.32–2.75) PFS (yrs) 1.00 (0.90–1.41) 1.53 (1.38–1.75) 1.80 (1.61–1.92) MRS (yrs) 2.98 (1.78–3.59) 3.30 (2.66–3.79) 2.90 (2.61–3.22) FPTD (yrs) 1.21 (0.76–1.91) 1.27 (0.84–2.02) 0.85 (0.68–1.07)