According to results published in the Journal of Clinical Oncology, early rituximab intensification during immunochemotherapy with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) does not improve outcome in patients with untreated diffuse large B-cell lymphoma (DLBCL).

The study, HOVON-84 (Haemato Oncology Foundation for Adults in the Netherlands), was an investigator-initiated, multicenter, prospective, randomized, phase 3 trial that compared the safety and efficacy of standard rituximab plus dose-dense 2-week CHOP (R-CHOP-14; 6 or 8 cycles) with those of treatment with rituximab intensification during the first 4 cycles of R-CHOP (RR-CHOP-14) in adult patients with DLBCL.

The primary endpoint was complete remission (CR) at the end of induction; additional outcomes of interest included progression-free survival (PFS), overall survival (OS), and failure-free survival (FFS).

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The intention-to-treat analysis included 574 patients, 286 in the R-CHOP-14 arm (median age, 66 years; range, 18-80 years) and 288 in the RR-CHOP-14 arm (median age, 65 years; range, 31-80 years). Patient characteristics among treatment arms were well balanced.

The treatment arms had no significant difference in the proportion of patients who achieved CR (89% vs 86% in R-CHOP-14 vs RR-CHOP-14, respectively; hazard ratio [HR], 0.82; 95% CI, 0.50-1.36; P =.44).

Similarly, after a median follow-up of 92 months (range, 1-131 months), the 3-year FFS (74% vs 69%, respectively; HR, 1.26; 95% CI, 0.98-1.61; P =.07), PFS (74% vs 71%; HR, 1.20; 95% CI, 0.94-1.55; P =.15), and OS (81% vs 76%; HR, 1.27; 95% CI, 0.97-1.67; P=.09) were not significantly different among the R-CHOP and RR-CHOP treatment groups.

Notably, patients who were older (between 66 and 80 years) experienced significantly more toxicity after the first 4 cycles of RR-CHOP-14 compared with the first 4 cycles of R-CHOP-14 (grade 4, 56% vs 40%, respectively; P =.007; grade 3-4, 73% vs 58%; P =.009). This group of patients also experienced significantly more grade 3 to 4 neutropenia (45% vs 32%; P =.04) in the RR-CHOP-14 arm compared with those in the R-CHOP-14 arm.

“For the past 2 decades, R-CHOP has remained the standard treatment for previously untreated DLBCL, and it has proven exceedingly difficult to improve on this baseline,” wrote the authors. “R-CHOP remains the standard treatment for DLBCL. Novel therapies are needed to improve the outcome of these patients.”

Disclosures: Some authors have declared affiliations with or received funding from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.


Lugtenburg PJ, de Nully Brown P, van der Holt B, et al. Rituximab-CHOP With Early Rituximab Intensification for Diffuse Large B-Cell Lymphoma: A Randomized Phase III Trial of the HOVON and the Nordic Lymphoma Group (HOVON-84). J Clin Oncol. Published online July 30, 2020. doi:10.1200/JCO.19.03418