R-CHOEP-14 Is Associated with Superior Overall Survival Compared to R-CHOP-21 and R-CHOP-14 in Patients with DLBCL ≤70 Years – a Swedish Lymphoma Registry Population Based Study

Background: The current standard treatment for patients with diffuse large B-cell lymphoma (DLBCL) is Rituximab - Cyclophosphamide, Doxorubicin, Vincristine, Prednisone (R-CHOP). Two large randomised trials have been unable to establish a significant difference in outcome between patients receiving R-CHOP at 21 versus 14 day intervals regardless of age (Cunningham et al Lancet 2013, Delarue et al Lancet 2013). Another means of intensifying R-CHOP is by the addition of etoposide (R-CHOEP-14). As of yet, no randomised study in the rituximab era has been performed specifically evaluating the addition of etoposide. The aim of this study was to compare the chemotherapy regimens used to treat DLBCL in Sweden (R-CHOP-21, R-CHOP-14, R-CHOEP-14) among patients aged ≤70 in terms of overall survival, adjusted for clinical prognostic factors.

Methods: The study population was identified through the Swedish Lymphoma Registry (SLR) 2007-2012. Data was analysed using STATA and SPSS. Age was modelled as splines in the multivariable analysis.

Results: A total of 1745 patients aged ≤70 were identified in the SLR during the time-frame of this study. Median age was 61 years (range 18-70). Of these, 1331 had received R-CHOP-21 (n=302), R-CHOP-14 (n=872) or R-CHOEP-14 (n=157) and were included in the study. Median follow-up time for surviving patients was 49 months. Three-year overall survival rates were 86.7%, 79.6% and 87.5% for the patients who received R-CHOP-21, R-CHOP-14 and R-CHOEP-14 respectively. There was a significant disparity in the distribution of prognostic factors among patients receiving the various chemotherapy regimens with a lower proportion of patients with elevated serum lactate dehydrogenase (S-LDH), performance status >1, stage III-IV and presence of bulky disease (>10 cm) in the R-CHOP-21 group compared to the other regimens. As expected, the most intensive regimen, R-CHOEP-14 was more frequently given to younger patients (median age 49) with high-risk prognostic features.

When adjusting for significant prognostic factors (age, performance status, S-LDH, bulky disease, stage and gender) in a multivariable Cox regression model, R-CHOEP-14 was found to be significantly superior both to R-CHOP-21 (Hazard Ratio (HR): 0.53, Confidence Interval (CI):0.3-0.9, p=0.026) and R-CHOP-14 (HR:0.63, CI:0.4-1.0, p=0.048). No significant difference between R-CHOP-14 and R-CHOP-21 was found (HR: 0.84, CI: 0.6-1.2, p=0.3), consistent with findings from randomised trials performed.

Conclusion: In this population based series of DLBCL, the more intensive regimen R-CHOEP-14 was associated with superior overall survival in patients aged up to 70 years, indicating that this may be considered among the standard treatment options for this patient population. R-CHOEP-14 should preferably be compared to R-CHOP-21 in a randomised setting in order to further elucidate which patient groups that benefit the most from treatment intensification.