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Reasons for cessation included progressive disease 52%; bridging to other therapy 10%; death 6%; toxicity 4%. 8 pts received up to 2 subsequent lines of therapy, with 2 receiving CAR-T therapy. B Introduction: b RRDLBCL outcomes remain poor despite autologous transplant and CAR-T therapies offering potential cure to a minority. POLATUZUMAB, BENDAMUSTINE & RITUXIMAB EFFICACY IN RELAPSED/REFRACTORY TRIAL-INELIGIBLE LARGE B CELL LYMPHOMA PATIENTS: AN AUSTRALIAN LYMPHOMA REGISTRY (LARDR) STUDY. [Extracted from the article]

Prior studies have suggested that immune thrombotic thrombocytopenic purpura (iTTP) may display seasonal variation; however, methodologic limitations and sample sizes have diminished the ability to perform a rigorous assessment. This 5-year retrospective study assessed the epidemiology of iTTP and determined whether it displays a seasonal pattern. Patients with both initial and relapsed iTTP (defined as a disintegrin and metalloprotease with thrombospondin type motifs 13 activity <10%) from 24 tertiary centers in Australia, Canada, France, Greece, Italy, Spain, and the US were included. Seasons were defined as: Northern Hemisphere-winter (December-February); spring (March-May); summer (June-August); autumn (September-November) and Southern Hemisphere-winter (June-August); spring (September-November); summer (December-February); autumn (March-May). Additional outcomes included the mean temperature in months with and without an iTTP episode at each site. A total of 583 patients experienced 719 iTTP episodes. The observed proportion of iTTP episodes during the winter was significantly greater than expected if equally distributed across seasons (28.5%, 205/719, 25.3%-31.9%; p = .03). Distance from the equator and mean temperature deviation both positively correlated with the proportion of iTTP episodes during winter. Acute iTTP episodes were associated with the winter season and colder temperatures, with a second peak during summer. Occurrence during winter was most pronounced at sites further from the equator and/or with greater annual temperature deviations. Understanding the etiologies underlying seasonal patterns of disease may assist in discovery and development of future preventative therapies and inform models for resource utilization., (© 2024 The Author(s). American Journal of Hematology published by Wiley Periodicals LLC.)

A decade after International Myeloma Working Group (IMWG) biomarkers (SLiM criteria) were introduced, this real-world study examined their impact on diagnosis, therapy and outcomes in myeloma. Using the ANZ MRDR, 3489 newly diagnosed patients from 2013 to 2023, comprising 3232 diagnosed by CRAB ('CRAB patients', including 1758 who also satisfied ≥1 SLiM criteria) and 257 by SLiM ('SLiM patients') criteria were analysed. CRAB patients had higher R-ISS and lower performance status, with no difference in cytogenetic risk. SLiM patients had improved progression-free survival (PFS, 37.5 vs. 32.2 months, hazard ratio [HR] 1.31 [1.08-1.59], p = 0.003), overall survival (80.9 vs. 73.2 months, HR 1.64 [1.26-2.13], p < 0.001) and PFS2 (54.6 vs. 40.3 months, HR 1.51 [1.22-1.86], p < 0.001) compared with CRAB patients, partially explained by earlier diagnosis, with no differential impact between the plasma cell and light-chain criteria on PFS. However, 34% of CRAB patients did not manifest SLiM characteristics, raising the possibility that SLiM features are associated with different biological behaviours contributing to a better prognosis, for example, improved PFS2 in SLiM patients suggested less disease resistance at first relapse. These data support earlier initiation of therapy by SLiM. The superior survival outcomes of SLiM versus CRAB patients highlight the importance of defining these subgroups when interpreting therapeutic outcomes at induction and first relapse., (© 2024 The Author(s). British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

KappaMab (KM; formerly MDX-1097) is a monoclonal antibody specific for the kappa myeloma antigen (KMA), a cell-surface antigen expressed on malignant plasma cells in kappa-restricted multiple myeloma (κMM), some lymphomas, occasional tonsillar B cells and in vitro activated B cells, but not on normal B cells in bone marrow. Phase I/IIa studies of single-agent KM confirmed a favourable toxicity profile and evidence of anti-myeloma activity. Ex-vivo studies demonstrating upregulation of KMA by lenalidomide, and enhanced effector-cell cytotoxicity provided the rationale for this phase IIb study where KM or KM in combination with lenalidomide and dexamethasone (KM-Rd) was administered in relapsed, refractory κMM patients. In addition, outcomes for a real-world matched case-control cohort from the Australian and New Zealand Myeloma and Related Diseases Registry (MRDR) who received Rd were compared to the KM-Rd cohort. KM-Rd demonstrated an overall response rate of 82.5% which compared favourably to the Rd-MRDR cohort of 45.1%. Both single-agent KM and KM-Rd regimens were well tolerated, with the KM-Rd safety profile similar to patients given only Rd in other clinical settings. Based on the excellent safety profile and significant efficacy, further clinical trials escalating the KM dose and pairing KM with other standard-of-care treatments are planned., (© 2023 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

The frequency and causes of early mortality in patients with newly diagnosed multiple myeloma (NDMM) have not been well described in the era of novel agents. We investigated early mortality in a prospective cohort study of all patients with NDMM registered on the Australian and New Zealand Myeloma and Related Diseases Registry (MRDR) at 36 institutions between July 2011 and March 2020. Early mortality was defined as death from any cause within the first 12 months after diagnosis. A total of 2377 patients with NDMM were included in the analysis, with a median (interquartile range) age of 67.4 (58.9-74.60 years, and 60% were male. Overall, 216 (9.1%) patients died within 12 months, with 119 (4.5%) having died within 6 months. Variables that were independent predictors of early mortality after adjustment in multivariable regression included age (odds ratio [OR] 1.07, 95% confidence interval [CI] 1.05-1.08; p < 0.001), Eastern Cooperative Oncology Group performance status (OR 1.50, 95% CI 1.26-1.79; p < 0.001), serum albumin (OR 0.95, 95% CI 0.93-0.98; p < 0.001), cardiac disease (OR 1.96, 95% CI 1.35-2.86; p < 0.001) and International Staging System (OR 1.40, 95% CI 1.07-1.82; p = 0.01). For those with a primary cause of death available, it was reported as disease-related in 151 (78%), infection 13 (7%), other 29 (15%). Infection was listed as a contributing factor for death in 38% of patients., (© 2022 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)