Background: Polatuzumab vedotin combined with R-CHP (Pola-R-CHP) has recently emerged as an alternative to R-CHOP for the frontline treatment of diffuse large B-cell lymphoma (DLBCL). However, real-world data regarding toxicity and survival outcomes following treatment with these regimens in newly diagnosed DLBCL patients utilizing propensity score matching is limited.

Methods: We conducted a retrospective real-world cohort study using TriNetX's United States (US) Collaborative Network. Adults (≥18 years) diagnosed with DLBCL between January 1, 2023, and July 1, 2024, who initiated either R-CHOP or Pola-R-CHP within this period, were included. Propensity score matching (1:1) was performed incorporating age, sex, comorbidities (type 2 diabetes mellitus, chronic kidney disease, and COPD), extranodal/organ involvement, and lactate dehydrogenase levels. Outcomes were assessed over a one year (1yr) window starting one day after treatment initiation and included chemotherapy-related toxicities, treatment with standard second-line therapy (axicabtagene ciloleucel, lisocabtagene maraleucel, tafasitamab or gemcitabine for all patients, as well as Pola for R-CHOP patients) as a surrogate for disease free survival, and mortality.

Results: 1476 patients treated with R-CHOP and 421 patients treated with Pola-R-CHP were identified and 421 patients per treatment group were analyzed after propensity score matching was performed. No statistically significant differences were observed in the incidence of toxicities between patients treated with R-CHOP as compared to Pola-R-CHP: neutropenia (41.6 vs. 44.4%, p=0.40), anemia (44.2% vs. 47.3%, p=0.37), pancytopenia (28.7% vs. 32.8%, p=0.20), thrombocytopenia (21.1% vs. 24.5%, p=0.25), fever (23.3% vs. 25.7%, p=0.42), sepsis (15.0% vs. 14.3%, p=0.77), polyneuropathy (23.3% vs. 27.8%, p=0.13), or constipation (30.2% vs. 29.0%, p=0.71).

Patients treated with R-CHOP were significantly more likely to receive second-line therapy within 1yr as compared to Pola-R-CHP (20.7% vs. 12.2%; OR 1.9, 95% CI 1.3–2.8, p=0.001). Second-line CART19 product utilization was similar between patients treated with R-CHOP as compared to Pola-R-CHP (4.0% vs. 6.5%, p=0.12). Second-line Pola was received by 12% of patients treated with R-CHOP.

Mortality at 1yr was similar between patients treated with R-CHOP vs Pola-R-CHP (12.6% vs. 12.4%, p=0.95). For patients treated with R-CHOP who then received second-line Pola, mortality at one year was 17.5%, which did not differ significantly from patients treated with Pola-R-CHP (p=0.26)

Conclusions: In this large real-world analysis of US patients with DLBCL treated with R-CHOP or Pola-R-CHP incorporating propensity score matching, key toxicity outcomes were similar. While survival at 1yr was similar between cohorts, patients treated with R-CHOP were more likely to receive second-line therapy within 1yr of treatment initiation as compared to patients treated with Pola-R-CHOP. As patients treated with R-CHOP followed by second-line Pola had similar rates of 1 yr survival as compared to patients treated with Pola-R-CHP, second-line Pola may benefit patients who did not receive this agent with first-line therapy. Future analyses of real-world databases, particularly those which contain data regarding DLBCL tumor features, may be able to identify characteristics associated with differential survival outcomes for DLBCL patients treated with R-CHOP as compared to Pola-R-CHP.

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2025
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