Dose-Adjusted EPOCH-R Compared With R-CHOP as Frontline Therapy for Diffuse Large B-Cell Lymphoma: Clinical Outcomes of the Phase III Intergroup Trial Alliance/CALGB 50303

Abstract

PURPOSE Alliance/CALGB 50303 (NCT00118209), an intergroup, phase III study, compared dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (DA-EPOCH-R) with standard rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) as frontline therapy for diffuse large B-cell lymphoma. PATIENTS AND METHODS Patients received six cycles of DA-EPOCH-R or R-CHOP. The primary objective was progression-free survival (PFS); secondary clinical objectives included response rate, overall survival (OS), and safety. RESULTS Between 2005 and 2013, 524 patients were registered; 491 eligible patients were included in the final analysis. Most patients (74%) had stage III or IV disease; International Prognostic Index (IPI) risk groups included 26% IPI 0 to 1, 37% IPI 2, 25% IPI 3, and 12% IPI 4 to 5. At a median follow-up of 5 years, PFS was not statistically different between the arms (hazard ratio, 0.93; 95% CI, 0.68 to 1.27; P = .65), with a 2-year PFS rate of 78.9% (95% CI, 73.8% to 84.2%) for DA-EPOCH-R and 75.5% (95% CI, 70.2% to 81.1%) for R-CHOP. OS was not different (hazard ratio, 1.09; 95% CI, 0.75 to 1.59; P = .64), with a 2-year OS rate of 86.5% (95% CI, 82.3% to 91%) for DA-EPOCH-R and 85.7% (95% CI, 81.4% to 90.2%) for R-CHOP. Grade 3 and 4 adverse events were more common ( P < .001) in the DA-EPOCH-R arm than the R-CHOP arm, including infection (16.9% v 10.7%, respectively), febrile neutropenia (35.0% v 17.7%, respectively), mucositis (8.4% v 2.1%, respectively), and neuropathy (18.6% v 3.3%, respectively). Five treatment-related deaths (2.1%) occurred in each arm. CONCLUSION In the 50303 study population, the more intensive, infusional DA-EPOCH-R was more toxic and did not improve PFS or OS compared with R-CHOP. The more favorable results with R-CHOP compared with historical controls suggest a potential patient selection bias and may preclude generalizability of results to specific risk subgroups.

Outcomes of patients with limited-stage aggressive large B-cell lymphoma with high-risk cytogenetics

“…19 Although the phase 3 Alliance/CALGB 50303 study did not show any outcome differences between R-CHOP and R-DA-EPOCH in DLBCL, only a limited number of patients with MYC-R (13 of 491) and DHL (3 of 491) were included, which precludes us from drawing any conclusions in this patient population. 21 In a recently published retrospective study of 171 LS-DLBCL patients treated with R-CHOP, with or without radiation therapy, patients with DHL (n 5 7) did not have an inferior PFS or OS. Definitive conclusions are difficult to be drawn given the low number of DHL patients.…”

Four versus six cycles of CHOP chemotherapy in combination with six applications of rituximab in patients with aggressive B-cell lymphoma with favourable prognosis (FLYER): a randomised, phase 3, non-inferiority trial

“…However, treatment did not change over time, but was confirmed because numerous randomised trials did not improve on R-CHOP. [28][29][30] Also, we found no evidence for a treatment by time interaction (appendix pp [21][22]. The WHO classification of lymphoma was modified three times since the study was started: the WHO classification of tumours of haemopoietic and lymphoid tissues revised fourth edition in 2017, made it essential to assign diffuse large B-cell lymphoma-not otherwise specified according to its cell of origin, either germinal centre B-cell-like or activated B-cell-like.…”

Australian and New Zealand consensus statement on the management of lymphoma, chronic lymphocytic leukaemia and myeloma during the COVID‐19 pandemic

“…We suggest weighing up the resources needed and the immunosuppression risks associated with intensified regimens, such as dose‐adjusted R‐EPOCH, particularly in those with low IPI and older patients who may experience increased toxicity. It may be reasonable to treat such patients with R‐CHOP (II,III) …”