Long-term outcomes after autologous stem cell transplantation for multiple myeloma

Abstract

As multiple myeloma (MM) treatments evolve, frequent updates are required to monitor the long-term effect of changes in approach. Traditionally, MM is considered an incurable disease, with most patients eventually relapsing. However, improvements in treatments has raised the possibility that MM might be functionally curable. To examine improvements in long-term survival, we followed 4329 patients with newly diagnosed MM treated with autologous stem cell transplantation (ASCT) at the University of Arkansas for Medical Sciences from 1989 through 2018. Overall survival (OS) and progression-free survival (PFS) were evaluated using Kaplan-Meier analysis, Cox proportional hazards models, relative survival analysis, and cure modeling among different time periods, risk groups, and demographic traits. Steady improvements in OS were found, with patients treated in 2014 or later having superior OS (hazard ratio, 0.35; 95% confidence interval [CI], 0.27-0.45) and reduced excess risk for MM death (relative excess risk, 0.30; 95% CI, 0.22-0.41) compared with patients treated in 1997 or earlier. Patients treated during intervening time periods often had intermediate survival, but trends in OS, PFS, and landmarked analyses were inconsistent. Cure models support the potential for cure, ranging from 6.3% to 31.3%, depending on the year of treatment, with 10.0% to 18.6% of patients achieving their normal life expectancy across multiple periods. There was some evidence of reductions in early mortality within 3 years of diagnosis, longer complete response (CR) duration, and reductions in relapse after achieving CR. However, results differed depending on age, risk group, and cytogenetic characteristics.

Graphical abstract

Figure 1.

OS and PFS in transplant-eligible patients. (A) OS Kaplan-Meier stratified by time period. (B) Three-year OS landmark Kaplan-Meier stratified by time period. (C) PFS Kaplan-Meier stratified by time period, restricted to patients on a TT protocol. (D) Three-year PFS landmark Kaplan-Meier stratified by time period, restricted to patients on a TT protocol. (E) OS Kaplan-Meier restricted to older patients. (F) OS Kaplan-Meier restricted to younger patients.

Figure 2.

Cumulative relative survival. (A) Cumulative relative survival restricted to patients younger than 65 years of age (n = 3123). (B) Cumulative relative survival restricted to patients 65 or older (n = 1206). Cumulative relative survival shows the ratio of the observed survival in the UAMS cohort, relative to the normal expected survival in the SEER life tables, matched on age, sex, year, and race/ethnicity. Downward sloping lines indicate consecutive years of follow-up where UAMS survival was worse compared with SEER survival. Lines that plateau indicate years where UAMS survival was similar to SEER survival and excess mortality from MM for the given years was approaching 0.