24 - High Dose Chemotherapy with Early Autologous Stem Cell Transplantation Compared to Standard Dose Chemotherapy or Delayed Transplantation in Patients with Newly Diagnosed Multiple Myeloma: A Meta-Analysis

Abstract

Background: Upfront high dose chemotherapy with stem cell transplantation (SCT) is often used for patients with newly diagnosed multiple myeloma (MM). This approach has shown variable benefits in various randomized clinical trials (RCTs) when compared to standard dose therapy (SDT) with or without delayed SCT. The aim of this meta-analysis was to evaluate difference in overall survival (OS) and progression-free survival (PFS) in various RCTs including patients who underwent high dose chemotherapy with early SCT compared to those who received SDT or delayed SCT. Methods: We searched different databases, including PubMed, Embase and Cochrane, to identify RCTs comparing early high dose therapy with autologous SCT versus SDT in patients with newly diagnosed MM. Efficacy outcome measures included were OS and PFS reported at the maximum follow-up period. The overall effect was pooled using the DerSimonian random effects model. A subgroup analysis was conducted to evaluate influence of the novel agents (e.g. immunomodulatory agents, proteasome inhibitors) on OS and PFS. Results: Twelve studies were identified, including a total of 3829 patients, which compared high dose chemotherapy with early SCT versus SDT/delayed SCT. Of these, 1824 patients were treated with early high dose chemotherapy and SCT while 2005 were treated with SDT or delayed SCT. Four of these included treatments with novel agents. Patients who received early SCT had no difference in OS compared to patients assigned to SDT or salvage SCT [hazard ratio .86 (95% CI .70-1.04)] (Figure 1). On the other hand, there was noted an improvement in PFS in patients who received early SCT [hazard ratio .73 (95% CI .56-.94)] (Figure 2). In a subgroup analysis of studies that utilized novel agents, both groups had similar outcomes in terms of OS [hazard ratio .85 (95% CI .46-1.6)] and PFS [hazard ratio .68 (95% CI .37-1.25)] (Figure 3).Figure 2Progression-free survival for all studies.View Large Image Figure ViewerDownload Hi-res image Download (PPT)Figure 3Overall survival and Progression-free survival for studies including novel agents.View Large Image Figure ViewerDownload Hi-res image Download (PPT) Conclusions: This analysis shows that over the years, early SCT was associated with a prolonged PFS but did not translate into a prolongation of OS, in patients with newly diagnosed MM. Our results show that in the era of novel agents, the benefit of early SCT is less clear; and for selected cases, delaying SCT remains an acceptable option.