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

Improvements in survival outcomes were seen among those at high risk for DLBCL who received 6x R-CHOP21 + 2R.

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

A staging bone marrow biopsy shows replacement of normal elements by diffuse large B-cell lymphoma, a type of non Hodgkin lymphoma

Image credit: © David A Litman | stock.adobe.com

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
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