Diffuse large B-cell lymphoma patients with early post diagnosis mortality at a quaternary care center.

e23078 Background: Treatment of diffuse large B-cell lymphoma (DLBCL) has seen significant advances over the last decade, including CAR-T, ADCs and bispecific antibodies, with improved disease control and survival. However, up to 20% of DLBCL patients (pts) die within a few months of diagnosis. We conducted a single institution retrospective study to identify demographics and clinical characteristics of this underserved population. Methods: We identified adult pts diagnosed with DLBCL between 2008 and 2023 from Cleveland Clinic’s lymphoma registry. PCNSL pts were excluded. Analysis included demographics, comorbidities, disease characteristics, treatment and outcomes. We defined early mortality (EM) as death within 100 days of diagnosis, based on findings from our prior SEER report (Diamond, ASH 2022) showing untreated pts have median survival of 3 months. Results: Among 462 pts with newly diagnosed DLBCL (Table 1), 84 (18.2%) had EM. Median survival for EM pts was 37 days vs. 37.5 months (p < 0.001). There were no differences in sex, race, income or distance to cancer center. EM pts had higher incidence and CIRS grading of cardiac (39% vs 22%, p = 0.004), respiratory (43% vs 35%, p = 0.016), intestinal (25% vs 21%, p = .014), liver (23% vs 12%, p = .050), and renal comorbidities (32% vs 13%, p < 0.001). They were more likely have ECOG 3 or higher (35% vs 8.5%, p < .001) and poor R-IPI score (85% vs 43%, p < 0.001). EM pts were older at diagnosis (75 vs 67 yrs, p < .001) and had more have bulky abdominal (29% vs 12%, p < .001) and extranodal disease (74% vs 58%, p = .006). Many EM pts (33%) were not prescribed therapy due to frailty (17%) or pt choice (7%). Full-dose anthracycline-based prescription rates were lower for EM pts (46% vs 69%, p < .001), with comparable use of dose-reduced anthracycline (i.e. R-miniCHOP) (8% vs 7.4%, p = 1) and higher non-anthracycline regimens. Disease progression was the leading cause of death in EM pts (52% vs 16 %, p < .0001), who also experienced higher non-cardiac treatment-related deaths (15% vs 3%, p < .0001). Treated EM pts had higher incidence of death due to acute treatment toxicity (20% vs .3%, p < .0001) and discontinuation of initial therapy due to toxicity (25% vs 10%, p = .005). Conclusions: The subgroup of DLBCL pts who die within 100 days of diagnosis is older and has more frequent and severe comorbidities. These pts present with advanced-stage disease and are either ineligible to receive therapy or rapidly experience severe toxicities of treatment, frequently resulting in death. These findings highlight a vulnerable group of DLBCL pts who currently lack safe and efficacious treatments. Clinical trials investigating novel therapeutic options for these pts are urgently needed. EM Non-EM P value B symptoms 51% 36% <.012 Albumin 3.1 4.0 <.001 LDH 551 260 <.001 Stage IV 68% 50% .017 >1 Extranodal site 49% 22% <.001 Lung site 18% 6.1% <.001 CNS site 9.5% 2.9% .0012 Liver site 18% 6.9% .001 Peritoneal site 11% .2% .002