Dose-Adjusted Etoposide, Prednisone, Vincristine, Cyclophosphamide, Doxorubucin and Rituximab (da-EPOCH-R) Vs Rituxan, Cyclophosphamide, Doxorubucin, Vincristine and Prednisone (R-CHOP) As First Line Treatment for Diffuse Large B-Cell Lymphoma (DLBCL)

Objectives:

To assess the efficacy and safety of da-EPOCH-R as frontline treatment for patients diagnosed with Stage III/IV Diffuse Large B-Cell Lymphoma.

Methods:

We conducted a retrospective study of newly diagnosed patients with advanced Diffuse Large B-Cell Lymphoma from January 2008 till September 2015, who received frontline da-EPOCH-R or R-CHOP at our Health System. We excluded patients with primary CNS lymphoma, primary testicular lymphoma and patients who received chemotherapy for a prior lymphoma.

25 patients who received da-EPOCH-R and 50 patients who received R-CHOP were identified. Da-EPOCH-R regimen consisted of Etoposide 50mg/m²/day, Doxorubucin 10mg/m²/day and Vincristine 0.4mg/m²/day given on Days 1-4, Cyclophosphamide 750mg/m² on Day 5, Prednisone 60mg/m² twice a day from Days 1-6 and Rituximab 375mg/m²given on Day 5. On Day 6 G-CSF was administered. Each cycle was given every 21 days for a total of 6 cycles. The dose of Etoposide, Doxorubucin and Cyclophosphamide was adjusted according to standard protocols. All patients on the da-EPOCH arm were on Acyclovir, Ciprofloxacin, Fluconazole and Trimethoprim-Sulfamethoxazole for anti-microbial prophylaxis during their treatment. The use of growth factors and anti-microbial prophylaxis was inconsistent in the R-CHOP arm.

Results:

When comparing the da-EPOCH-R arm versus the R-CHOP arm, the average age of the patients was 50 years (25-81) vs 60 years (19-84). High-risk IPI was similar in both arms (76% vs 74%). The percentage of non-germinal center type (non-GCB) was equal as well (36% vs 32%). The average number of cycles administered was 5.3 compared to 4.8. There were more dose reductions in the da-EPOCH-R arm (36% vs 24%), however fewer delays and cessations were noted (36% vs 54%).

After a median follow up of 29.1 months, the age-adjusted overall survival (77% vs. 69%, p=0.093) and disease-free survival (76% vs. 55% p=0.54) was improved in the da-EPOCH-R arm. In the non-GCB variant da-EPOCH improved overall survival by 77% (p=0.024). The Overall Response Rate was higher in the da-EPOCH-R arm 80% (CR/CRU=64% and PR=16%) vs. 56% (CR/CRU=44% and PR=12%). The relapse rate was lower in the da-EPOCH-R arm (16% vs 28%), and it was lower in the non-GCB patients as well (11% vs 25%). There were more Grade 3-4 neutropenia in the da-EPOCH arm (72% vs 48%), however infectious complications were lower (24% vs 42%). There were fewer unplanned admissions in the da-EPOCH arm (32% vs 60%) and a significantly lower treatment related mortality (12% vs 22%). Other Grade 3-4 toxicities too were lower in the da-EPOCH-R arm (20% vs 30%). Conclusion:

Our preliminary results suggest that da-EPOCH-R has a survival benefit especially in the non-GCB subgroup. Our data does show good survival data even for the GCB subtypes. There was a higher response rate, lower relapse rate and no added toxicities in patients who received da-EPOCH-R. A Phase III trial is currently ongoing and will provide us with answers regarding the efficacy and toxicities of this chemotherapy regimen.