Title:Dose-Adjusted EPOCH Plus Rituximab (DA-EPOCH-R) in Untreated Patients with Poor Risk Large B-Cell Lymphoma. A Phase 2 Study Conducted by the Spanish PETHEMA Group.

Since the development of CHOP chemotherapy, many efforts have been made to improve first line treatment in aggressive lymphomas, mainly in poor prognosis cases. To assess the efficacy and safety of an infusional DA-EPOCH plus Rituximab (DA-EPOCH-R) regimen in poor prognosis large B-cell lymphomas, the Spanish PETHEMA group conducted a phase 2 study in patients with a higher than 1 aaIPI in this setting.

Eligibility criteria included histologically documented DLBCL, grade 3b follicular lymphoma or primary mediastinal B-cell lymphoma, IPI higher than 2 or aaIPI higher than 1 (or equal to 1 plus bulky disease). No restriction was made based on ECOG performance status when they could understand and sign the informed consent. Radiation therapy as consolidation was permitted on bulky masses detected at diagnosis.

Herein, 71 patients were evaluated for safety and outcome: 32 were male and 39 female. Median age was 60 years (range: 21-77). DLBCL was diagnosed in 57 (80%), PMBCL in 6 (9%), and grade 3b follicular lymphoma 8 (11%). Eighty nine percent had advanced (III-IV) CS, and 58% presented B symptoms. Bulky disease (³ 10 cm maximum diameter) was present in 18%. ECOG was higher than 2 in 13 patients (18%). b-2-microglobulin was elevated in 62%, and LDH in 90% of patients. AaIPI was: 1 in 7 patients (10%), 2 in 36 (51%), and 3 in 28 (39%). Four hundred and fifteen cycles were given. A grade 3-4 mucositis occurred in 9 occasions, and neutropenic fever or infections in 66 cycles (16%). Fifty nine patients (83%) achieved a CR or CRu, 6 (8%) a PR and 4 (6%) an inadequate response, there were 2 early deaths: a toxic one, due to septic shock, and one due to non-related cause (traumatism). Twenty six percent of patients who achieved a CR relapsed. Twenty one patients (30%) died so far: 76% due to progressive disease, one patient who had undergone an ASCT after relapse died from secondary MDS. With a median follow-up of 40 months the event-free survival and overall survival is 60% and 61% respectively at 5 years. Disease-free survival is 72% at 5 years for patients who achieved a CR or CRu. No statistically significant difference in overall survival were seen according to aaIPI risk factors.

DA-EPOCH-R is an immunochemotherapy regimen with a clinically significant activity and a very acceptable toxicity profile in patients with poor prognosis aggressive B-cell lymphomas and could somehow overcome IPI risk factors.

No relevant conflicts of interest to declare.