/home/tah 81Introduction Diffuse large B-cell lymphoma (DLBCL) with co-expression of MYC and BCL2 protein by immunohistochemistry (IHC) (i.e. doubleexpresser lymphoma, DEL) and/or rearrangements of MYC and BCL2 or BCL6 genes (i.e. double-hit lymphoma, DHL) is associated with poor outcomes after standard frontline therapy, independent of other clinical risk factors. [1][2][3][4] Less is documented concerning the impact of these genetic events in relapsed/refractory disease. R-ICE (rituximab, ifosfamide, carboplatin and etoposide) is an active regimen for patients with relapsed/refractory DLBCL and can effectively mobilize hematopoietic progenitor cells for subsequent autologous stem cell transplantation (ASCT). 5 R-ICE followed by ASCT is a common salvage approach for medically fit patients with relapsed/refractory DLBCL. In this study, we investigated the prognostic impact of DEL in the salvage setting by analyzing outcomes of patients with relapsed/refractory disease treated with R-ICE prior to planned ASCT.
Patients and methodsWe reviewed records of 204 consecutive patients with DLBCL treated with salvage R-ICE and intent for ASCT from 2000 to 2015 at the Taussig Cancer Institute of the Cleveland Clinic. A total of 37 patients were excluded for inadequate clinical data and/or follow up. Data were collected from the electronic medical record with IRB approval. Abstract: Diffuse large B-cell lymphoma (DLBCL) with co-expression of MYC and BCL2 protein by immunohistochemistry (IHC) -that is, double-expresser lymphoma (DEL) -is associated with poor outcomes after standard frontline therapy. Less is known about the prognostic impact of DEL in patients with relapsed/refractory disease treated with salvage therapy and autologous stem cell transplantation (ASCT). We analyzed the outcomes of 167 patients with relapsed/refractory DLBCL treated with R-ICE (rituximab, ifosfamide, carboplatin and etoposide), of whom 111 patients (66%) underwent ASCT. Using predefined cutoffs for positivity by IHC at relapse for MYC and BCL2 of ⩾40% and ⩾50% of positive tumor cells, respectively, 26 patients (16%) were categorized as DEL and the rest as non-DEL. Overall and complete response rates to R-ICE did not differ between DEL and non-DEL. With a median follow up of 20 months, the 3-year progression-free survival (PFS) and overall survival (OS) rates for DEL were inferior compared to non-DEL (for PFS: 6% versus 33%, p = 0.044, for OS: 39% versus 56%, p = 0.03). The negative impact of DEL on PFS and OS remained significant on multivariable analysis. In conclusion, positive DEL status predicts poorer outcomes following salvage therapy.