Outcomes after (90) Yttrium-ibritumomab tiuxetan-BEAM in diffuse large B-cell lymphoma: a meta-analysis

Abstract

High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is a standard therapy in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) who are chemosensitive. The combination of carmustine, etoposide, cytarabine, and melphalan (BEAM) is commonly used as a conditioning regimen. The addition of yttrium-90 ((90) Y)-ibritumomab tiuxetan (Zevalin(®)) to BEAM (Z-BEAM) is increasingly being used to improve outcomes and overcome refractory disease. We conducted a literature review and meta-analysis in order to evaluate the clinical effects of Z-BEAM followed by ASCT in patients with DLBCL. A literature search was conducted for randomized controlled trials and observational studies of Z-BEAM as a conditioning regimen for ASCT in adult patients with DLBCL. Extracted data included baseline patient demographics, overall response (ORR), complete response (CR), overall survival (OS), progression-free survival (PFS), nonrelapse mortality (NRM), median time to ANC and platelet engraftment, and rate of myelodysplastic syndrome. Mixed-effects models were used to determine estimates. Ten studies (N = 328) were included in the meta-analysis. The 2-year OS and PFS were 84.5% (n = 328) and 67.2% (n = 285), respectively. Outcomes were superior in patients with nontransformed lymphoma. Posttransplant, ORR and CR rates were 72.6% and 68.5%, respectively. The NRM rate was 6.3% and the incidence rate of myelodysplastic syndrome was 2.5%. Two-year OS was significantly associated with pretransplant ORR (P = 0.008, τ(2) = 0). There was no significant association between PFS and pretransplant response. Z-BEAM is safe and effective as a conditioning regimen in relapsed/refractory DLBCL.

Keywords: 90Y-Ibritumomab tiuxetan; DLBCL; Z-BEAM; autologous transplantation; meta-analysis; radioimmunotherapy.

Figure 1

Flow diagram of the trial selection process.

Figure 2

Forest plot of OS at 2 years (A), OS at 2 years defined by transformed (T) or not transformed (NT) (B), OS at 2 years defined by prospective (Prosp) or not prospective (No Prosp) studies (C). Heterogeneity is estimated with I² statistic according to Higgins et al. and Higgins and Thompson . By group analysis for both NT/T and Prosp/No prosp is made by mixed-effects analysis. OS, overall survival.

Figure 3

Forest plot of PFS at 2 years (A), PFS at 2 years defined by transformed (T) or not transformed (NT) (B), PFS at 2 years defined by prospective (Prosp) or not prospective (No Prosp) studies (C). Heterogeneity is estimated with I² statistic according to Higgins et al. and Higgins and Thompson . By group analysis for both NT/T and Prosp/No prosp is made by fixed-effects analysis. OS, overall survival; PFS, progression-free survival.

Figure 4

Measured (circle) and predicted (line) 2-year OS depending on the difference in pretransplant ORR in mixed-effects metaregression analysis. ORR, overall response; OS, overall survival.

Figure 5

Funnel plot of natural logarithm of 2-year OS. Results are based on the 10 included studies for 2-year OS (open circles) and with the addition of three virtual studies identified by “trim-and-fill” analysis (black circles) (Egger et al. , Duval and Tweedie, 16). OS, overall survival.

Figure 6

Funnel plot of natural logarithm of 2-year PFS. Results are based on the nine included studies for 2-year PFS (open circles) and with the addition of one virtual study identified by “trim-and-fill” analysis (black circles) (Egger et al. , Duval and Tweedie 16). PFS, progression-free survival.

Figure 7

(A) Forest plot of OS at 2 years. Meta-analysis for trials comparing BEAM with Z-BEAM under fixed method. (B) Forest plot of PFS at 2 years. Meta-analysis for trials comparing BEAM with Z-BEAM under fixed method. Heterogeneity is estimated with I² statistic according to Higgins et al. and Higgins and Thompson . OS, overall survival; PFS, progression-free survival.