Early Rituximab Intensification in R-CHOP for Diffuse Large B-Cell Lymphoma

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As reported in the Journal of Clinical Oncology by Pieternella Johanna Lugtenburg, MD, PhD, and colleagues, the phase III Haemato-Oncology Foundation for Adults in the Netherlands (HOVEN)/ Nordic Lymphoma Group HOVON-84 trial showed that early rituximab intensification in R-CHOP-14 (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) did not improve the rate of complete remission vs standard R-CHOP-14 in patients with diffuse large B-cell lymphoma (DLBCL).

Pieternella Johanna Lugtenburg, MD, PhD

Pieternella Johanna Lugtenburg, MD, PhD

Study Details

The trial included 574 patients aged 18 to 80 with previously untreated disease from sites in the Netherlands, Denmark, and Belgium. Patients were randomly assigned between November 2007 and April 2012 to receive six or eight cycles of rituximab-intensified R-CHOP-14 (RR-CHOP-14; n = 286) or standard R-CHOP-14 (n = 288). Rituximab intensification consisted of rituximab at 375 mg/m2 on both day 1 (standard regimen) and day 8 (intensification) of 14-day cycles for the first four cycles. The primary endpoint was complete remission at the end of induction in the intention-to-treat population.


At least six cycles were received by 94% of patients in the R-CHOP-14 group and 91% of patients in the RR-CHOP-14 group, and seven or eight cycles were received by 53% and 55%.


  • RR-CHOP-14 did not improve complete remission rate vs R-CHOP-14.
  • No differences were observed in failure-free, progression-free, or overall survival.

Complete remission was achieved in 249 (86%) of 288 patients in the RR-CHOP-14 group vs 254 (89%) of 286 patients in the R-CHOP-14 group (hazard ratio [HR] = 0.82, 95% confidence interval [CI] = 0.50–1.36, P = .44). No significant differences in rates of complete remission were observed among patients aged < 60 years (85% vs 90%) or those aged ≥ 66 years (88% vs 88%).

Median follow-up was 92 months. Failure-free survival at 3 years was 69% in the RR-CHOP-14 group vs 74% in the R-CHOP=14 group (HR = 1.26, 95% CI = 0.98–1.61, P = .07). Progression-free survival at 3 years was 71% vs 74% (HR = 1.20, 95% CI = 0.94–1.55, P =.15). Overall survival at 3 years was 76% vs 81% (HR = 1.27, 95% CI = 0.97–1.67, P = .09).  

Adverse Events

Grade 3 or 4 adverse events occurred in 75% of the RR-CHOP-14 group and 70% of the R-CHOP-14 group. The most common events in the RR-CHOP-14 group were neutropenia (40% vs 47%), infection (25% vs 24%), anemia (19% vs 19%), neurologic toxicity (14% vs 14%), and gastrointestinal toxicity (14% vs 13%). During the first four cycles in patients age 66 to 80, rates of grade 3 or 4 toxicity were higher in the RR-CHOP-14 group (73% vs 58%), particularly neutropenia (45% vs 32%) and infections (25% vs 19%).

The investigators concluded: “Early rituximab intensification during R-CHOP-14 does not improve outcomes in patients with untreated DLBCL…. R-CHOP remains the standard treatment for DLBCL. Novel therapies are needed to improve the outcome of these patients.”

Dr. Lugtenburg, of the Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by the Dutch Cancer Society and Roche Nederland. For full disclosures of the study authors, visit

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