Death from mantle cell lymphoma limits sequential therapy, particularly after first relapse: Patterns of care and outcomes in a series from Australia and the United Kingdom

Mantle cell lymphoma (MCL) is a B-cell non-Hodgkin lymphoma characterised by a heterogeneous clinical course. Patients can often receive sequential treatments, yet these typically yield diminishing periods of disease control, raising questions about optimal therapy sequencing. Novel agents, such as chimeric antigen receptor T-cell therapies and bispecific antibodies, show promise in relapsed MCL, but are often reserved for later treatment lines, which may underserve patients with aggressive disease phenotypes who die early in the treatment journey. To assess the problem of patient attrition from lymphoma-related death limiting sequential treatment, we performed a multicentre retrospective cohort analysis of 389 patients treated at Australian and UK centres over a 10-year period. Deaths from MCL increased after each treatment line, with 7%, 23% and 26% of patients dying from uncontrolled MCL after first, second and third lines respectively. Patients with older age at diagnosis and early relapse after induction therapy were at particular risk of death after second-line treatment. This limitation of sequential treatment by lymphoma-related death provides support for the trial of novel therapies in earlier treatment lines, particularly in high-risk patient populations

The Influence of Immunodeficiency, Disease Features and Patient Characteristics on Survival in Plasmablastic Lymphoma

Plasmablastic lymphoma (PBL) is a rare and aggressive non-Hodgkin lymphoma associated with immunodeficiency, characterized by uncertain treatment approaches and an unfavourable prognosis. We conducted a multicenter, international, retrospective cohort study, aiming to characterize the clinical features, risk factors, and outcomes of patients with PBL. Data were collected from 22 institutions across four countries regarding patients diagnosed with PBL between 1 January 1999 and 31 December 2020. Survival risk factors were analyzed using both univariate and multivariate regression models. Overall survival (OS) was calculated using Kaplan-Meier statistics. First-line treatment regimens were stratified into standard- and higher-intensity regimens, and by whether they incorporated a proteasome inhibitor (PI). A total of 281 patients (median age 55) were included. Immunodeficiency of any kind was identified in 144 patients (51%), and 99 patients (35%) were HIV-positive. The five-year OS for the entire cohort was 36% (95% CI 30-42%). In multivariate analysis, inferior OS was associated with EBV-negative lymphoma, poor performance status, advanced stage, and bone marrow involvement. In an independent univariate analysis, the IPI was associated with OS outcomes. Neither immunosuppression, nor HIV infection specifically, influenced OS. Among patients treated with curative intent (n=234), the overall response rate was 72%. Neither the intensity of the treatment regimen nor the inclusion of PIs in first-line therapy was associated with OS. In this large retrospective study of PBL patients, we identified novel risk factors for survival. PBL remains a challenging disease with poor long-term outcomes

The influence of immunodeficiency, disease features, and patient characteristics on survival in plasmablastic lymphoma

Plasmablastic lymphoma (PBL) is a rare and aggressive non-Hodgkin lymphoma associated with immunodeficiency, characterized by uncertain treatment approaches and an unfavourable prognosis. We conducted a multicenter, international, retrospective cohort study, aiming to characterize the clinical features, risk factors, and outcomes of patients with PBL. Data were collected from 22 institutions across four countries regarding patients diagnosed with PBL between 1 January 1999 and 31 December 2020. Survival risk factors were analyzed using both univariate and multivariate regression models. Overall survival (OS) was calculated using Kaplan-Meier statistics. First-line treatment regimens were stratified into standard- and higher-intensity regimens, and by whether they incorporated a proteasome inhibitor (PI). A total of 281 patients (median age 55) were included. Immunodeficiency of any kind was identified in 144 patients (51%), and 99 patients (35%) were HIV-positive. The five-year OS for the entire cohort was 36% (95% CI 30-42%). In multivariate analysis, inferior OS was associated with EBV-negative lymphoma, poor performance status, advanced stage, and bone marrow involvement. In an independent univariate analysis, the IPI was associated with OS outcomes. Neither immunosuppression, nor HIV infection specifically, influenced OS. Among patients treated with curative intent (n=234), the overall response rate was 72%. Neither the intensity of the treatment regimen nor the inclusion of PIs in first-line therapy was associated with OS. In this large retrospective study of PBL patients, we identified novel risk factors for survival. PBL remains a challenging disease with poor long-term outcomes