POD24 in Mexican Patients with Diffuse Large B-Cell Lymphoma (DLBCL): Real-World Experience with Long Follow-up
Authors: Candelaria Myrna , Aviles Alejandro , Gutierrez Olga , Castillo Jorge J. 
Published: December 2024

Background: Chemoimmunochemotherapy (CIT) is the standard for treating patients with diffuse large B-cell lymphoma (DLBCL) with a curative intent. However, up to 40% of patients will relapse. The outcomes of DLBCL patients who experience early disease progression are dismal. Data on the outcomes of DLBCL patients with disease progression within 24 months of treatment initiation (POD24) in Latin American patients are lacking.

Methods: We designed a retrospective study to evaluate the outcomes of patients with DLBCL who experienced early disease progression on standard CIT. Inclusion criteria were adult patients with a pathological diagnosis of DLBCL treated at a reference center in Mexico who attained a response after frontline CIT. HIV-positive patients, CNS involvement, follow-up time less than 24 months without relapse, and death within 24 months without evidence of lymphoma were excluded from the analysis. The study's main objective is to determine the impact of POD24 on overall survival (OS). Demographic characteristics are reported using descriptive statistics. The OS was calculated from the time of early progression for the POD24 group or 2 years after diagnosis for the reference group. Survival curves were estimated using the Kaplan-Meier method. Cox proportional-hazard regression models were fit to evaluate factors influencing OS, such as gender, albumin level, International Prognostic Index (IPI) score, molecular subtype by the Hans nomogram, and POD24.

Results: 602 patients with DLBCL treated between 2011 to 2018 were included. The data cutoff was December 2023. From them, 473 attained a complete response. 15 cases without relapse were excluded because of a follow-up of less than two years. 458 were included in this analysis. The median age was 56 years (range 19-96). 240 patients (52%) were female, 360 (79%) had an ECOG 0-1, 360 (79 %) had serum albumin &lt;3.5 g/dl, 137 (30 %) had a non-germinal center (NGC) Hans profile, and 291 (63%) had high and high-intermediate IPI scores. Standard R-CHOP was the schema most frequently indicated (n=404; 85%). Seventy-one patients relapsed, 38 before 24 months (POD24 group), and 33 after that time (POD after 24); 387 cases did not relapse (No POD). There were no differences in gender, serum albumin levels, IPI score, and NGC profile between patients with relapse before or after POD24. When only patients who relapse were compared by univariate analysis , the factors influencing mortality were: NGC by Hans nomogram (HR 1.9, 95 % CI: 1.3 -2.4) and POD24 (HR 5.2, CI: 2.8 -9.4; p= 0.008). After multivariate analysis, these factors remained statistically significant: NGC by Hans nomogram (HR 1.8, 95 % CI: 1.1 -2.9; p=0.01) and POD24 (HR 5.2, CI: 2.8 -9.4; p=0.01). When comparing patients with POD24 and patients without relapse, the following factors were statistically significant, by univariate analysis: NGC by Hans nomogram (HR 1.7, 95 % CI: 1.3 -2.4; p&lt;0.001), high/high-intermediate IPI score (HR 1.3, 95% CI 1.1-1.7; p=0.006;) and POD24 (HR 5.2, CI: 2.8 -9.5, p &lt; 0.001).

Conclusions: This real-world analysis shows that DLBCL patients treated with CIT who attained a complete response but experienced POD24 had a worse outcome than those patients who experienced disease progression after 24 months or did not relapse. POD24 in DLBCL was not associated with gender, serum albumin level, IPI score, or Hans profile. Other clinicopathological mechanisms must play a role in early disease progression in DLBCL.