Survival of patients newly diagnosed with mayo stage iiia/iiib cardiac light chain amyloidosis on a bortezomib- or daratumumab-based therapy by isotype: results from a single site retrospective study

Background Light chain amyloidosis (AL) is a rare hematologic disorder. In AL, abnormal light chains from a clonal plasma cell dyscrasia (PCD) produce toxic amyloid fibrils that cause systemic organ dysfunction, thus high morbidity and mortality. AL is managed with anti-PCD therapies aiming to decrease the production of light chains and subsequent fibril deposition. Recommended first-line therapy includes cyclophosphamide-bortezomib-dexamethasone (CyBorD) with/without daratumumab. Patients with advanced AL, as defined by cardiac biomarkers per the European modified Mayo 2004 stage, are at high risk of death. Little is known about current patient outcomes by light chain isotype (kappa, lambda). The objective of this analysis was to assess overall survival of newly diagnosed, previously untreated AL patients with advanced cardiac stage initiating bortezomib- or daratumumab-based regimens in a single site in Greece. Methods This retrospective analysis included newly diagnosed adult patients with Mayo stage IIIa/IIIb AL who initiated on therapy ("index date") between 2018-2024 at our university. Patients receiving stem cell transplant, other amyloidosis forms, or in a clinical trial were excluded. The primary outcome of all-cause mortality was measured using Kaplan-Meier survival methods to generate survival probability as well as time to death, which were assessed in the overall population, and stratified by Mayo stage and isotype. Results A total of 104 patients met eligibility criteria, of which the majority were male (N=60; 57%) and a mean age of 67.8 years (SD=9.9); 54% (N=56) and 46% (N=48) were classified as European modified Mayo stage IIIa and IIIb, respectively. 29 (28%) and 75 (72%) of patients were identified as kappa and lambda isotype, respectively. The most common index treatment regimen was CyBorD (N=43; 41%), followed by CyBorD+daratumumab (N=32; 31%) and daratumumab monotherapy (N=27; 28%). Patients had follow-up for minimum of 2 weeks to a maximum of 362 weeks post-index. At 12 months post-index, the overall mortality was 37% with a mean time-to-death of 19.6 (SD=12.8) weeks. When stratified by isotype, 12-month mortality for the kappa and lambda overall patient population were 42% and 37%, respectively. When further stratified by stage, 12-month mortality for the kappa/lambda patients were 20%/22% (IIIa) & 64%/50% (IIIb), respectively. Discussion: This analysis assessed the survival among newly diagnosed AL patients with advanced disease who started on anti-PCD therapy, overall and when stratified by isotype in a single site database analysis. Mortality over the follow-up period varied depending on severity of disease and isotype, with higher mortality seen among kappa Mayo stage IIIb patients. High rates of mortality within certain patient categories underscore a significant unmet need that remains despite advances in treatment paradigms.