No Major Differences Identified Between R-CHOP21 Regimens for Treatment of Advanced-Stage Diffuse Large B-Cell Lymphoma

No significant differences were observed in event-free survival (EFS) and overall survival (OS) between treatment with 6 cycles of rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP)21 or 6 cycles of R-CHOP21 with 2 additional administrations of rituximab (6x R-CHOP21 + 2R) for patients with advanced-stage diffuse large B-cell lymphoma (DLBCL), according to an analysis published in Blood Cancer Journal.¹

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R-CHOP’s introduction in the early 2000s has led to a significant increase in survival among patients with DLBCL, regardless of disease stage or age. It is now the preferred first-line treatment approach for most patients with DLBCL, though over the last 2 decades, adjustments have been made to the treatment regimen. These include dose intensity and cycle reductions.^1,2

These advancements are based on data from clinical trials and population-based studies. Now, the standard of care for most patients with advanced-stage DLBCL is considered 6 cycles of R-CHOP, administered every 21 days. However, it remains unclear whether 2 additional cycles of rituximab should be applied, as no randomized comparison between 6x R-CHOP21 and 6x R-CHOP21 + 2R has been conducted.^1,2

In this trial, the investigators sought to examine the effectiveness between these treatment options in patients with advanced-stage DLBCL in the Netherlands. The results will allow the effectiveness of these treatments to be fully explored in a real-world setting, offering a unique perspective on managing this disease across different risk profiles.¹

EFS and OS of the treatments were conceptualized utilizing Kaplan-Meier curves, displaying the survival probability at each point in time. The investigators restricted the follow-up to 5 years to ensure optimal estimates. A univariable Cox proportional hazards model was used to quantify the relative effect of the treatment on patients.¹

In total, 1577 patients were included in the study; 672 (43%) were treated with 6x R-CHOP21, and 905 (57%) received 6x R-CHOP21 + 2R. For all patients, median EFS time was 4.44 (IQR: 3.84-5.32) years and median OS time was 4.44 (IQR: 3.84-5.29). In addition, there were mostly males in the study cohort.¹

Complete remission at end of treatment was achieved in most patients (87%), and there were no significant differences found between treatment groups. Participants who were treated with 6x R-CHOP21 + 2R compared with 6x R-CHOP21 were older, had a worse stage of disease, and had regional differences in the allocation of treatment.¹

Regarding EFS, the measurement did not significantly differ between patients treated with either regimen (HR = 0.89; 95% CI: 0.72-1.09). Five-year absolute risk difference (ARD) was 4.2% (95% CI: -3.6-11.9%); individuals receiving 6x R-CHOP21 + 2R were expected to have events 0.14 years later than those treated with 6x R-CHOP21 (95% CI: -0.04-0.33) over a 5-year period.¹

Similarly, OS was not significantly different between patients treated with either regimen (HR = 0.93; 95% CI: 0.73-1.18). Five-year ARD was 1.3% (95% CI: -6.3-9.0%); participants who received 2 additional rituximab cycles possibly lived 0.11 years longer (95% CI, -0.05-0.27) over a 5-year period compared with those who did not receive extra treatments.¹

The findings of the study suggest that no significant differences exist in patients treated with either regimen, yet in patients who are considered high-risk, there was a suggestion of improved overall survival outcomes when treated with 6x R-CHOP21 + 2R. These findings align with those from previous trials, including one conducted by Wang et al.^1,3

Those investigators demonstrated microenvironmental and molecular profiles in high-risk categories, which could explain the differences in survival outcomes and treatment responses. They specifically single out MCD- and ST2-like subtypes in the lymphoma microenvironment that were associated with poorer clinical outcomes, supporting the argument that these patients need more intense treatment.³

It is important to note that this trial was conducted in the absence of interim PET scan treatment guidance. Applying interim PET scan results could modify the outcomes found in the trial.¹

“These findings underscore the potential for augmented treatment approaches in DLBCL, particularly for those with a higher prognostic risk,” the study investigators concluded. “However, given the limitations related to unmeasured confounders, future population-based research should focus on validating our study findings in the context of interim PET-guided treatment.”¹

REFERENCES

1. Maas CCHM, van Klaveren D, Durmaz M. et al. Comparative effectiveness of 6x R-CHOP21 versus 6x R-CHOP21 + 2R for patients with advanced-stage diffuse large B-cell lymphoma. Blood Cancer J. 2024:157(14). doi:10.1038/s41408-024-01137-0

2. Issa DE, Dinmohamed AG, Wondergem MJ, et al. A population-based study on different regimens of R-CHOP in patients with newly diagnosed DLBCL in The Netherlands. Leukemia & Lymphoma. 2020:62(3):549-559. doi:10.1080/10428194.2020.1842394

3. Wang Y, Shi Q, Shi ZY, et al. Biological signatures of the International Prognostic Index in diffuse large B-cell lymphoma. Blood Adv. 2024:8(7):1587-1599. doi:10.1182/bloodadvances.2023011425