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Summary: 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. [ABSTRACT FROM AUTHOR]

Summary: 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. [ABSTRACT FROM AUTHOR]