Long‐term follow‐up of dose‐adjusted EPOCH plus rituximab (DA‐EPOCH‐R) in untreated patients with poor prognosis large B‐cell lymphoma. A phase II study conducted by the Spanish PETHEMA Group

Abstract

SummaryThis prospective multi-institutional phase II study was designed to assess the efficacy and safety of dose-adjusted EPOCH (etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin) plus rituximab (DA-EPOCH-R) in untreated patients with poor prognosis large B-cell lymphomas. Eighty-one patients diagnosed with diffuse large B-cell lymphoma (DLBCL, n = 68), primary mediastinal DLBCL (n = 6) and follicular lymphoma Grade 3b (n = 7), with an age-adjusted International Prognostic Index >1, were eligible for analysis. Median age was 60 years (range: 21-77). Sixty-five patients (80Á2%) achieved complete response. After a median follow-up time of 64 months, 10-year event-free survival and overall survival (OS) were 47Á8% and 63Á6%, respectively. None of the studied clinical and biological characteristics were associated with poorer outcome. Interestingly, patients with BCL6 rearrangement achieved a 10-year OS of 100%, while patients with BCL2 rearrangement exhibited a poorer outcome compared to activated B-cell tumours and germinal centre B-cell without BCL2 rearranged tumours. Results achieved with DA-EPOCH-R showed a good long-term outcome and a tolerable toxicity profile in high-risk large B cell lymphoma patients. Outcome was not affected by tumour cell proliferation or by cell of origin, highlighting the requirement of new biological markers for patient subclassification of high-risk DLBCL patients.

A comparison of R-EPOCH and R-CHOP as a first-line regimen inde novoDLBCL patients with high Ki-67 expression in a single institution

“…The limited number of patients in the high-risk group might be one of the reasons for these negative results. The efficacy of R-EPOCH regimen in high-risk DLBCL patients is still uncertain [10, 36], which needs to be explored in the prospective studies. A phase III randomized study of comparison R-CHOP and R-EPOCH regimen in treating DLBCL in the US is still ongoing, and we are expecting the final results.…”

“…However, some DLBCL patients continue to present an inferior prognosis under standard R-CHOP therapy. Therefore, many studies have been performed in an attempt to improve the current treatment for DLBCL with a poor prognosis [8–10]. …”

Factors and Costs Associated With Delay in Treatment Initiation and Prolonged Length of Stay With Inpatient EPOCH Chemotherapy in Patients With Hematologic Malignancies

“…Each EPOCH cycle was analyzed separately, so a single patient may have had multiple treatment cycles. The following exclusion criteria were used: Inpatient cycles with a delay of EPOCH initiation of >7 days from admission, which likely represented an admission for reasons other than EPOCH administration, and cycles in which patients were treated with additional chemotherapy agents, with the exception of rituximab and/or bortezomib, since these agents may be given with EPOCH (16, 17, 19, 22, 24, 25, 34–36). EPOCH cycles were classified on the basis of their setting (inpatient vs. outpatient).…”

Rituximab with dose-adjusted EPOCH as first-line treatment in patients with highly aggressive diffuse large B-cell lymphoma and autologous stem cell transplantation in selected patients

“…In 2007, a Spanish group reported using R-DA-EPOCH for the treatment of poor prognosis DLBCL patients and achieving 2-year OS and event-free survival (EFS) rates of 75% and 68%, respectively, with aaIPI≥3 as the only factor related to poor EFS (21). Recently, another group from Spain reported 10-year OS and EFS rates of 64% and 48%, respectively, in R-DA-EPOCH-treated patients with poor prognosis DLBCL (33). ASCT has been extensively discussed as part of first-line therapy for aggressive non-Hodgkin lymphomas, especially DLBCL (26,34-36), where consolidation using high-dose therapy and ASCT was shown to reduce relapse rate, mainly in a subgroup of high-risk patients (37-39).…”