Efficacy of Autologous and Allogeneic Hematopoietic Cell Transplantation in Waldenström Macroglobulinemia: A Systematic Review and Meta-Analysis

Abstract

Background Waldenstrom macroglobulinemia (WM) is an indolent IgM-producing lymphoproliferative disorder that remains incurable. Although it is an indolent disease, patients with a high international prognostic scoring system (IPSS)-WM have an overall survival (OS) of less than 4 years. Furthermore, 15% of IPSSWM low-risk patients also develop progressive disease after achieving remission with first-line therapy. Both autologous hematopoietic cell transplantation (AHCT) and allogeneic (allo)-HCT are prescribed for treatment of WM despite lack of randomized controlled studies. Methods We performed a comprehensive search of the medical literature using PubMed/Medline and EMBASE on September 10, 2019. We extracted data on clinical outcomes related to benefits (OS, progression-free survival [PFS] and overall response rate [ORR]) and harms (relapse rate [RR] and non-relapse mortality [NRM]), independently by two authors. Our search strategy identified a total of 339 references. Fifteen studies (8 AHCT [n=291 patients], 7 allo-HCT [n=311 patients]) were included in this systematic review/meta-analysis (Figure 1). Results Median age for AHCT recipients ranged from 49 to 60 years. 58% and 41% of AHCT recipients received melphalan and BEAM conditioning respectively. Pooled OS rate post AHCT was 70% (95% CI=51-87%) with high heterogeneity (I2=87%). Pooled PFS rate post AHCT was 50% (95% CI 38%-61%) with moderate heterogeneity (I2=59%). Pooled NRM was 4% (95% CI 1-7%) with low heterogeneity (I2=0%). In the case of allo-HCT recipients, the median age ranged from 43 to 57 years and 52% received a reduced intensity conditioning regimen. Pooled OS rate post allografting was 57% (95% CI 50-65%) with low heterogeneity (I2=19%). Pooled PFS was 49% (95% CI 42-56%) with low heterogeneity (I2=15%). Pooled NRM was 29% (95% CI 24-34%) with low heterogeneity (I2=0%) (Figure 2). Pooled ORR post AHCT and allo-HCT were 90% (95% CI 82-96%) and 86% (95% CI 76%-95%) respectively, both with moderate heterogeneity. RR post AHCT and allo-HCT was 42% (95% CI 30-55%) and 23% (95% CI 18-28%) respectively, both with moderate heterogeneity, respectively (Figure 3). Conclusions The results of our meta-analysis show that both AHCT and allo-HCT result in encouraging OS and PFS. Allo-HCT does appear to have circa 2-fold lower risk of relapse compared to AHCT based on our analysis. This potential advantage of allografting is offset by a higher NRM. Large multicenter prospective studies are needed to determine which WM patient population would derive the most benefit from an allo-HCT.