Autologous stem cell transplant (ASCT) for newly diagnosed multiple myeloma (MM) in the era of novel agents: A meta-analysis of phase III randomized controlled trials.

Abstract

8022 Background: Given the unprecedented deep response rates with the novel agent induction, the role of high dose therapy (HDT) followed by ASCT in MM pts. has been questioned, and was re-evaluated in a number of randomized clinical trials (RCTs). Although, the results of most studies suggest the continued benefit of HDT/ASCT, some RCTs suggest no overall survival (OS) benefit. We undertook a systematic review and meta-analysis of phase III randomized RCTs evaluating the role of HDT compared to standard therapy (SDT) in the context of novel agent induction Methods: We searched the PubMed, Scopus and Cochrane Collection of Controlled Trial databases using the term myeloma combined with autologous or transplant or myeloablative or stem cell from 2000-2016. A total of 2480 articles identified, of which 4 large phase III RCTs compared upfront HDT with SDT with novel agents use. Two individuals independently extracted the data. Reported hazard ratio (HR) and survival data were pooled using random effects models (STATA v14, College Station, Tx). Heterogeneity was assessed using I2. Results: Four studies comprising 2421 patients were included (Table 1). One study did not report the HR for death and hence OS analysis was limited to 3 studies. The combined hazard for progression with HDT was 0.55 (95% CI 0.40-0.71) (p < 0.005). The combined hazard for death with HDT was 0.65 (95% CI 0.29-1.0) (p = 0.007). Sensitivity and sub-group analysis showed no difference in PFS (p = 0.06) and OS (p = 0.22) with HDT. Significant heterogeneity was demonstrated by I2 of 71.4% for PFS (p = 0.01) and 68.4% for OS (p = 0.04). Conclusions: Based on our analysis, even in the novel agent era, HDT appears to be beneficial and should be considered standard of care for all transplant eligible MM pts. [Table: see text]