Barriers to First-Line Therapy in Plasmablastic Lymphoma: A Retrospective Study in a Middle-Income Country
Authors: Pellon Tellez Irma Karen , Rubalcava Luis Felipe , Fernandez Vargas Omar Eduardo , Cetina Castro Gilda Coralia , Castellanos Mares Mistral , Bonilla Salcedo Andres Yesid Yesid , Cesarman-Maus Gabriela N. , Acosta Maldonado Brenda Lizeth 
Published: December 2024

Introduction: Plasmablastic lymphoma (PBL) is a rare and aggressive B-cell lymphoma that predominantly affects individuals with HIV/AIDS or those in immunosuppressed states. Characterized by plasma cell-like features, loss of mature B-cell markers, and often associated with Epstein-Barr Virus [1]. PBL exhibits poor outcomes, even in the era of antiretroviral therapy (ART). Notably, limited access to first-line therapy is a significant concern, with reports indicating that between 14% and 28% of patients with newly diagnosed PBL receive no treatment [2,3]. Our study aims to identify the factors contributing to this lack of access to therapy.

Methods: We conducted a single-center retrospective study to identify factors associated with limited access to first-line therapy in adult patients diagnosed with PBL between 2011 and 2022, encompassing individuals aged 18 to 100 years. The clinico-biological and demographic characteristics of patients receiving first-line therapy were compared to those of patients who did not receive therapy.

Results: A total of 88 patients with PBL were included, with a male predominance (89.8%) and a median age at diagnosis of 41 years. The majority of patients exhibited advanced stage disease (80.7%). A total of 15 (17%) patients faced barriers to accessing first-line therapy and were unable to receive treatment, mainly due to early death after diagnosis. Factors associated with lack of therapy were characterized by poorer performance status (ECOG ≥2; p=0.035), lower albumin levels (p=0.0201), and reduced lymphocyte counts (p=0.0011). Most patients had an HIV-associated PBL (78.4%, n=69), however, more than half of these patients (55%) were diagnosed concurrently or in the following three months after HIV diagnosis, while the rest (n=31) had a median time from HIV diagnosis to PBL of 45 (4-146) months. Although HIV-positive status did not significantly influence treatment access, a history of virologic failure (p=0.0435) and not receiving ART (p&lt;0.0001) was strongly associated with lack of therapy. Age was not a factor for lack of therapy (median 41 vs 46 years; p=0.623).Multivariate analysis revealed that worse ECOG scores and bulky disease influenced OS, while other IPI factors were not significant.

Conclusions: Roughly one in every five patients with newly diagnosed PBL faced barriers to accessing first-line therapy, including compromised performance status, low albumin levels, and lymphocytopenia, often in the context of advanced-stage disease, all of which were associated with early mortality. Among HIV-positive patients, virologic failure and the absence of ART were significant barriers to receiving therapy. Notably, more than half of these patients were diagnosed with HIV and PBL concurrently, highlighting the need for HIV screening programs.

References:

1.- Li, J. W., Peng, H. L., Zhou, X. Y., & Wang, J. J. (2024). Plasmablastic lymphoma: current knowledge and future directions. Frontiers in immunology, 15, 1354604. https://doi.org/10.3389/fimmu.2024.1354604

2.- Tchernonog, E., Faurie, P., Coppo, P., Monjanel, H., Bonnet, A., Algarte Génin, M., Mercier, M., Dupuis, J., Bijou, F., Herbaux, C., Delmer, A., Fabiani, B., Besson, C., Le Gouill, S., Gyan, E., Laurent, C., Ghesquieres, H., & Cartron, G. (2017). Clinical characteristics and prognostic factors of plasmablastic lymphoma patients: analysis of 135 patients from the LYSA group. Annals of oncology : official journal of the European Society for Medical Oncology, 28(4), 843-848. https://doi.org/10.1093/annonc/mdw684

3.- Makady, N. F., Ramzy, D., Ghaly, R., Abdel-Malek, R. R., & Shohdy, K. S. (2021). The Emerging Treatment Options of Plasmablastic Lymphoma: Analysis of 173 Individual Patient Outcomes. Clinical lymphoma, myeloma & leukemia, 21(3), e255-e263. https://doi.org/10.1016/j.clml.2020.11.025