Background: Daratumumab, an immunoglobulin G kappa (IgG-κ) monoclonal antibody, can co-migrate with endogenous M-protein on serum immunofixation (IF), producing IgG-κ bands that may be misinterpreted as residual disease. We therefore evaluated treatment responses and the prognostic impact of daratumumab-associated IgG-κ IF positivity on progression-free survival (PFS) and overall survival (OS) in multiple myeloma (MM). Methods: We retrospectively analyzed 108 patients with MM treated with daratumumab-containing regimens at any line of therapy between January 2014 and January 2024. Serum IF IgG-κ positivity was assessed both at the first response assessment and during continued treatment. Treatment responses were classified according to the International Myeloma Working Group (IMWG) criteria, and PFS and OS were analyzed using the Kaplan–Meier method, the log-rank test, and multivariable Cox proportional hazards regression. Results: IgG-κ IF positivity was detected in 85 patients (78.7%) at first response, and the overall response rate to daratumumab was 64.8%. Patients positive at first response had longer PFS (14.0 vs. 7.0 months; P = 0.048) and higher very good partial response/complete response rates (65.9% vs. 43.5%; P = 0.058). In non–IgG-κ myeloma, treatment-emergent positivity was associated with a markedly higher deep-response rate (88.5% vs. 44.2%; P < 0.001) and a reduced risk of progression (hazard ratio 0.17; 95% confidence interval 0.03–0.74; P = 0.018). On multivariable analysis, older age independently predicted mortality, whereas persistent IF positivity did not worsen survival. Conclusions: IgG-κ IF positivity during daratumumab therapy should not be interpreted as residual disease in isolation; a substantial proportion likely reflects therapeutic antibody interference. Recognizing this interference is important to avoid overestimating residual disease and misclassifying treatment response, and confirmatory assays should be used where available.
Introduction: Post-transplant erythrocytosis following allogeneic hematopoietic stem cell transplantation (allo-HSCT) is rare and has been reported mainly in patients with aplastic anemia and, less frequently, after transplantation for other hematologic conditions. Here, we present two cases of JAK2V617F-positive polycythemia vera (PV) developing after allo-HSCT performed for chronic myeloid leukemia (CML) and myelodysplastic syndrome (MDS). Case presentations: Case 1: The patient, who underwent allo-HSCT for the diagnosis of MDS. He was diagnosed with JAK2V617F-positive PV, 48 months after transplantation. Case 2: The patient with chronic-phase CML underwent allo-HSCT while in hematologic remission. Approximately 10 years later, the patient was diagnosed with JAK2V617F-positive PV. Discussion: Possible explanations for the development of a JAK2V617F mutation after allo-HSCT include the expansion of a pre-existing but clinically silent mutant clone in the donor, or the emergence of de novo mutations in donor or recipient cells as a result of proliferative stress, immunosuppression, or prior chemotherapy.
Background: Multiple Endocrine Neoplasia type 1 (MEN1) is an autosomal dominant tumor predisposition syndrome involving primary hyperparathyroidism (PHPT), pituitary neuroendocrine tumors (PitNETs), and pancreatic neuroendocrine tumors. MEN1-associated insulinomas may present with multifocal disease, complicating management, while Cushing's disease is uncommon, and the coexistence of multiple functioning tumors complicates management. Case presentation: A 28-year-old man presented with adrenocorticotropic hormone-dependent hypercortisolism and progressive cushingoid features. Pituitary Magnetic Resonance Imaging revealed a microadenoma, confirmed as a PitNET on histopathology. Concurrent PHPT and genetically confirmed MEN1 (splice-site pathogenic variant c.825-1G>A) were identified. Transsphenoidal surgery failed to achieve remission, and metyrapone provided partial control. Subtotal parathyroidectomy resulted in persistent PHPT. Imaging revealed multifocal pancreatic NETs with biochemically confirmed insulinoma. Lanreotide achieved complete resolution of hypoglycemia, while Ga-68-NOTA-exendin-4 positron emission tomography/computed tomography did not identify a dominant lesion, supporting conservative management. Conclusion: This case highlights the complexity of MEN1 with multiple functioning tumors and the clinical impact of hormonal interactions. It underscores the importance of multidisciplinary, individualized management, particularly when tumor multifocality limits surgical options. It also emphasizes the need to recognize complex endocrine syndromes in general clinical practice.
Background: The cornerstones of secondary prevention in chronic coronary syndrome (CCS) are blood pressure lowering and lipid-lowering therapy (LLT). The purpose of this study was to examine the control of systolic blood pressure (SBP) and low-density lipoprotein cholesterol (LDL-C) in patients with CCS followed in primary care. Methods: This was a retrospective population-based cohort study of patients diagnosed with CCS at cardiology clinics in Uppsala Region, Sweden, between 2012 and 2020. Data from electronic health records were analyzed for SBP and LDL-C monitoring and secondary prevention target achievement during 3 years of follow-up, stratified by sex, age, and diabetes status. Sex differences in time to LLT initiation during the first year after CCS diagnosis were evaluated using Cox proportional hazards models. Results: In total, 1,452 patients (415 women and 1,037 men) were followed for a median of 3.2 years (interquartile range [IQR]: 1.4-5.8). Most patients had at least one SBP measurement during follow-up, and approximately half met SBP targets (50.9% of women and 56.1% of men at year 1). LDL-C monitoring was less common: at year 1, 40.8% of women and 28.7% of men lacked a measurement, and targets were achieved in 12.1% of women and 24.7% of men. By year 3, target achievement had declined further to 11.2 and 15.0%, respectively. Women were less likely than men to initiate LLT within the first year (adjusted hazard ratio 0.70, 95% confidence interval: 0.61-0.80, P < 0.001). LLT use also declined over time, with 54.1% of women versus 73.9% of men on treatment at year 3 (P < 0.001). Conclusion: Large gaps in secondary prevention of patients with CCS were observed, with under-monitoring of LDL-C and declining use of LLT, particularly among women. Although SBP was routinely assessed, only half of patients achieved recommended levels. These findings highlight the need for systematic strategies in primary care to improve management in CCS.
Background: The introduction of immune checkpoint inhibitor (ICI) treatment has significantly improved the treatment of several cancer diagnoses, such as non-small cell lung cancer, renal and urothelial carcinoma, melanoma. However, there is a lack of real-world data on ICI treatment and outcomes from the Swedish healthcare setting. The cost of treatment is also significant, and securing equal access to emerging drugs for all patients is challenging in an era of rapidly evolving treatment recommendations. Methods: We conducted a population-based observational study of incident cases among ICI-treated patients, using a novel electronic healthcare record source for systemic cancer drugs linked to regional and national register data. Overall survival (OS) was calculated from start of the first ICI-treatment, using the Kaplan-Meier method. The aim was to examine treatment with ICI drugs during 2015–2023 in 10 Swedish regions (total population 4.3 million). Results: Median real-world OS was 2.0 years (95% confidence interval: 1.8–2.2 years) from start of ICI-treatment for patients with known palliative treatment intent (n = 1,941, lung 2.2 years, melanoma 5.0 years, renal 2.3 years, urothelial 1.1 years, head/neck 1.4 years). In 2023, 6.7% of all patients receiving systemic antineoplastic treatment for cancer were treated with ICI (74 per 100,000 inhabitants). The timing of the adoption of treatment with ICI drugs and the current patterns of use differed between Swedish regions. Conclusion: This study provides the first Swedish real-world OS estimates after ICI-treatment across major diagnoses, documents the rapidly increasing ICI use, and describes regional variation in treatment patterns.
