Comparative Efficacy of Tandem Autologous Versus Autologous Followed by Allogeneic Hematopoietic Cell Transplantation in Patients with Multiple Myeloma: A Systematic Review and Meta-Analysis

Despite advances in our understanding of clinical, genetic, and molecular aspects of multiple myeloma (MM) coupled with availability of more effective therapies, it remains an incurable disease. Combining cytoreduction from high-dose (chemo- or chemoradio-) therapy with adoptive immunotherapy forms the basis of an autologous-allogeneic (auto-allo) hematopoietic cell transplantation (HCT) strategy. However, when an auto-allo HCT approach is compared to tandem autologous (auto-auto) HCT, conflicting results have been reported. Accordingly, we performed a systematic review of published studies comparing auto-auto HCT with auto-allo HCT in patients with newly diagnosed MM.

A systematic search of MEDLINE thru Nov 5, 2011, and pertinent conference proceedings, was conducted. Included studies allocated newly diagnosed MM patients to auto-allo HCT if an HLA-matched sibling donor was available versus auto-auto if sibling donor was not available (biologic randomization). Independent, dual data extraction was performed. Pooling of data from similar outcomes was done using the random-effects model.

Our search identified 152 publications, of which five (manuscript=four, abstract=one) met inclusion criteria. The five included trials enrolled 1538 patients (auto-allo=565, auto-auto=973). At least a very good partial response was assessed in one study (522 patients) and did not differ among the treatment arms [risk ratio (RR) (95% CI) = 0.97 (0.87–1.09), p=0.66]; but complete remission, assessed in five studies (1130 patients), was higher in the auto-allo HCT arm [RR(95% CI) =1.65 (1.25–2.19), p=0.0005]. Event-free survival did not differ among auto-allo HCT group versus auto-auto HCT group on per-protocol analysis [hazard ratio (HR) (95% CI) = 0.78 (0.58–1.05)), p=0.11] of three trials (409 patients), or ITT analysis [HR(95% CI) = 0.83 (0.60–1.15), p=0.26] in three trials (1229 patients). Overall survival (OS) did not differ among these treatment arms whether analyzed on per-protocol [HR(95% CI) = 0.88 (0.33–2.35), p=0.79] in two trials (214 patients), or by ITT [HR(95% CI) = 0.80 (0.48–1.32), p=0.39] analysis in three trials (1229 patients). Non-relapse mortality (NRM) was worse with auto-allo HCT [RR(95%CI) = 3.55 (2.17–5.80), p<0.00001] in four trials (1047 patients).

Despite higher CR rates, there is no apparent improvement in OS with auto-allo HCT; but this approach results in higher NRM in patients with newly diagnosed MM.

No relevant conflicts of interest to declare.