Impact of cell of origin on outcomes after autologous hematopoietic cell transplant in diffuse large B-cell lymphoma

Abstract Germinal center B-cell-like diffuse large B cell lymphoma (GCB-DLBCL) at diagnosis is associated with superior long-term outcomes compared to non-GCB-DLBCL in patients treated with conventional chemo-immunotherapy. Whether cell of origin (COO) by Hans algorithm retains its prognostic significance in patients with (R/R) relapsed/refractory DLBCL undergoing autologous hematopoietic cell transplant (auto-HCT) is not well established. Three hundred and fifty-seven patients underwent auto-HCT between 2005 and 2018. The COO status was determined in 284 patients and these were included in the analysis. One hundred ninety-four patients had GCB-DLBCL while 90 had non-GCB-DLBCL. Median follow up was 1.7 (0-13) years. The GCB-DLBCL was associated with inferior 5-year overall survival at 44% (95%CI, 36 to 52) versus (vs) 64% (95%CI, 54 to 77) (p=0.004) and a higher relapse incidence at 67% (95%CI, 58 to 74) vs 49% (95%CI, 35 to 60)(p=0.01) in the non-GCB-DLBCL. The difference between GCB and non-GCB-DLBCL remained statistically significant in multivariate analysis. Additionally, response at the time of transplant was an independent prognostic factor. GCB-DLBCL was enriched in double-hit and triple hit phenotype based on available fluorescence in situ hybridization data. These results suggest an enrichment of high-risk genetic rearrangements in R/R GCB-DLBCL resulting in limited efficacy of auto-HCT. Key points 1. GCB-DLBCL is associated with worse outcomes in patients with R/R DLBCL undergoing auto-HCT Clinical Practice Points 1. GCB-DLBCL is associated with worse outcomes in patients with R/R DLBCL undergoing auto-HCT 2. There is enrichment of high-risk genetic rearrangements in R/R GCB-DLBCL resulting in limited efficacy of auto-HCT