Matched control analysis suggests R-CHOP followed by (R)-ICE may improve outcome in non-GCB DLBCL compared to R-CHOP

• Intensified non-cross-resistant sequential R-CHOP followed by (R)-ICE may improve outcome in non-GCB DLBCL.

• The immunohistochemistry-based Hans algorithm may be used to stratify patients with DLBCL into prognostic subgroups.

Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) is considered the standard-of-care for patients with advanced-stage diffuse large B-cell lymphoma (DLBCL), despite findings that non-germinal center B-cell-like (non-GCB) patients have significantly worse outcome with this regimen. We evaluated the prognostic significance of baseline risk factors, including cell of origin (COO) classified by the Hans algorithm, within an alternative chemoimmunotherapy program. At Memorial Sloan Kettering Cancer Center (MSK), 151 patients with DLBCL received sequential R-CHOP induction and (R)-ICE (rituximab, ifosfamide, carboplatin, and etoposide) consolidation. Outcome analysis based on COO was validated with a propensity score matched cohort treated with R-CHOP from the Mayo Clinic component of the Molecular Epidemiology Resource (MER). Among the GCB (n=69) and non-GCB (n=69) patients at MSK, event-free survival (EFS) of non-GCB was superior to that of GCB (HR 0.53, 95% CI 0.29-0.98). Overall survival (OS) demonstrated an association in the same direction but was not statistically significant (HR 0.68, 95% CI 0.33-1.42). Propensity score matched patients from MSK (n=108) demonstrated a small attenuation in the HRs for EFS (HR 0.57, 95% CI 0.27-1.18) and OS (HR 0.76, 95% CI 0.33-1.79) and were no longer statistically significant. In contrast, the matched MER cohort (n=108) demonstrated an EFS association (HR 1.17, 95% CI 0.70-1.95) and OS association (HR 1.13, 95% CI 0.64-2.00) in the opposite direction, but were also not statistically significant. R-CHOP induction and (R)-ICE consolidation may overcome the negative prognostic impact of the non-GCB phenotype, per the Hans algorithm, and can be preferentially selected for this population.