Effectiveness and infectious complications of BCMA T-cell engagers in treating multiple myeloma: Real-world evidence from Sweden.

BACKGROUND: Multiple myeloma (MM), an incurable disease characterized by frequent relapses and a need for multiple treatments, often progresses to a relapse/refractory status resistant to all available drugs and drug classes. Bispecific antibodies, specifically BCMA T-cell engagers, have emerged as effective treatments for MM, demonstrating impressive efficacy. However, these treatments can adversely affect the immune system, increasing vulnerability to infections. METHODS/RESULTS: This study evaluated the efficacy and safety of BCMA T-cell engagers in 58 Swedish patients with poor MM prognosis. The patients exhibited a 69% overall response rate, with 69% survival and 60% progression-free survival at 15 months. CONCLUSIONS: Despite the risk of infectious complications, the prognosis of MM patients can be significantly improved with vigilant monitoring and proactive management of infections. This real-world data highlight the potential of BCMA T-cell engagers in treating MM, emphasizing the need for careful patient monitoring to mitigate infection risks.

Impact of 1q gains on treatment outcomes of patients with newly diagnosed multiple myeloma in a real-world Swedish population receiving modern treatment.

BACKGROUND: Amplification of 1q (amp(1q); ≥4 1q copies) has repeatedly been reported to predict a worse outcome in multiple myeloma (MM), whereas the impact of gain of 1q (gain(1q); three 1q copies) is less clear. METHODS: We investigated survival of MM in relation to amp(1q) and gain(1q) by retrospectively analysing 346 consecutively newly diagnosed MM (NDMM) patients. Of these, 62 (18%) had amp(1q), 97 (28%) gain(1q) and 187 (54%) a normal number of 1q copies (no1q). RESULTS: The patients with amp(1q) had a shorter median progression-free survival than those with gain(1q) or no(1q) (13.1 months, 95% confidence interval [CI] 8.2-18.1 months vs. 36.1 months, 95% CI 23.1-49.1 months vs. 25.4 months, 95% CI 19.8-31.1 months, p = .005). The 3-year overall survival (OS) was 56% for amp(1q), 76% for gain(1q) and 80% for no1q (p = .003). In the multivariate analysis, the presence of amp(1q) was independently associated with a shorter OS (hazard ratio 1.99, 95% CI 1.03-3.82, p = .039), whereas gain(1q) had no negative effect on survival. CONCLUSION: Our results thus suggest that amp(1q) should be considered a high-risk abnormality in NDMM and that new treatment strategies should be explored to mitigate its negative effect on survival.

A rare case of IgE kappa monoclonal gammopathy of undetermined significance identified in a Swedish female.

Monoclonal gammopathies involving immunoglobulin E (IgE) is a very rare phenomenon, with less than 70 cases being previously described in the literature. The IgE monoclonal gammopathies include malignant plasma cell disorders such as IgE multiple myeloma (MM), as well as the associated premalignant condition IgE monoclonal gammopathy of undetermined significance (MGUS). We report a case of a 41-year-old woman presenting with an IgE kappa monoclonal protein following routine laboratory testing. Serum protein electrophoresis (SPEP) initially showed a monoclonal protein in the beta-2 fraction, at an estimated concentration of <4 g/L. Subsequent serum immunofixation electrophoresis (SIFE) including antisera to Ig heavy chains delta and epsilon confirmed the presence of an IgE kappa monoclonal protein. Analysis of serum free light chains (FLCs) showed increased levels of kappa FLC, resulting in an abnormally elevated kappa/lambda FLC ratio. No Bence-Jones proteinuria was present. Bone marrow aspiration showed 6% plasma cells, and no sign of myeloma-associated end-organ damage was evident. Consequently, the patient was diagnosed with IgE kappa MGUS. In the present report, the clinical characteristics of the patient are compared to previous descriptions of IgE monoclonal gammopathy. The report further emphasizes the importance of considering the presence of monoclonal IgD or IgE when SIFE shows a clear band positive for a light chain but is negative for Ig heavy chains gamma, alpha and mu.

Direct evidence for a polygenic etiology in familial multiple myeloma.

Although common risk alleles for multiple myeloma (MM) were recently identified, their contribution to familial MM is unknown. Analyzing 38 familial cases identified primarily by linking Swedish nationwide registries, we demonstrate an enrichment of common MM risk alleles in familial compared with 1530 sporadic cases (P = 4.8 × 10-2 and 6.0 × 10-2, respectively, for 2 different polygenic risk scores) and 10 171 population-based controls (P = 1.5 × 10-4 and 1.3 × 10-4, respectively). Using mixture modeling, we estimate that about one-third of familial cases result from such enrichments. Our results provide the first direct evidence for a polygenic etiology in a familial hematologic malignancy.