Efficacy of Dose-Dense R-CHOP-14 Chemoimmunotherapy Plus Pegfilgrastim for First-Line Treatment of Diffuse Large B-Cell Lymphoma (DLBCL) in Low Risk Patients: An Interim Analysis of an Open-Label Clinical Trial in Spain. On Behalf of GEL/TAMO (Spanish Group of Lymphoma).

Diffuse large B-cell lymphoma (DLBCL) is the most prevalent form of non-Hodgkin lymphoma. The addition of rituximab to the standard treatment with 3-weekly CHOP (R-CHOP) has notably improved the survival in DLBCL. However, it is unclear whether a dose-dense regimen of 2-weekly R-CHOP-14 is efficacious and well tolerated. The aim of the current study is to determine the efficacy and tolerability of 6 cycles of dose dense R-CHOP-14 for low risk DLBCL. This is an ongoing, open-label, multicentre, single-arm clinical trial. Eligible patients are aged 18–65 years, with CD20+ DLBCL, an international prognostic index (IPI) of 0–2 and an Eastern Cooperative Oncology Group (ECOG) performance status of 0–2. Six cycles of R-CHOP-14 are administered with pegfilgrastim 6 mg sc on day 2 of each cycle. Patients with tumor masses > 10 cm are allowed to receive radiotherapy with 30 Gy, and those at risk of central nervous system infiltration receive prophylactic liposomal cytarabine with each chemotherapy cycle. An interim analysis of efficacy was planned when the first 25 patients were included. Patients receiving ≥1 dose of study medication were included in the tolerability analysis, while 130-day follow-up was required for inclusion in the efficacy analysis. The first 25 patients were included between June 2006 and January 2007: mean age was 46.5 years, 56% were male. The characteristics of the disease at diagnosis were as follows: stage III-IV 40%, ECOG 0–1 96%, B-symptoms 12%, bulky disease 28%, extranodal involvement 56% (most frequently spleen and gastrointestinal system), elevated LDH 44%, elevated β₂microglobulin 36%, IPI 0–1 60%. All patients completed 6 cycles of chemotherapy (150 cycles). Among the 125 cycles excluding the first one, there were 7 (5.5%) delays, 3 because of neutropenic fever, 2 because neutropenia, and 2 because of infection without neutropenia. Dose modification due to hematological toxicity occurred in 4 cycles (3.2%) all in the same patient. Twenty-two patients were included in the efficacy analysis. The global response rate, the complete remission rate and the partial remission rate were 91%, 81.8% and 9.1%, respectively. No patient exhibited disease progression or relapse, whereas 2 (9.1%) had stable disease. All 22 patients were alive at 130 days follow-up. In this interim analysis, high remission rates suggest that dose dense R-CHOP-14 with pegfilgrastim support is an efficacious treatment for low risk DLBCL in patients younger than 65. The regimen was well tolerated with most patients completing their full treatment schedule as planned.