Background and Objectives: Ixazomib, used in combination with lenalidomide and dexamethasone (IRd), has shown efficacy in clinical trials for relapsed/refractory multiple myeloma (RRMM). Materials and Methods: This study evaluates the real-world effectiveness and safety of IRd in Croatian RRMM patients. A retrospective analysis was conducted on 164 RRMM patients treated with ixazomib at nine Croatian haematology centres from November 2016 to February 2023. Data on patient demographics, treatment regimens, and outcomes were collected and analysed using Kaplan–Meier survival curves and Cox proportional hazards models in R. The median age at ixazomib initiation was 66 years (range 40–91). Results: The overall response rate (ORR) was 65.8%, with 42% of patients achieving a very good partial response (VGPR) or better. The median progression-free survival (PFS) was 15.4 months, while median overall survival (OS) was 28.2 months. Hematologic toxicities included anaemia (53%), neutropenia (50%), and thrombocytopenia (45%). Infective complications, primarily COVID-19 and pneumonia, were reported in 38% of patients. The safety profile was consistent with previous studies, indicating manageable adverse events. Ixazomib-based therapy is effective and well tolerated in a real-world Croatian RRMM population. Conclusions: The findings align with clinical trial results, demonstrating the applicability of ixazomib in routine clinical practice. Further studies are needed to optimise treatment sequencing and improve patient outcomes.

Background/Objectives: In hematological patients receiving treatment for lymphomas, febrile neutropenia (FN) is a serious complication associated with significant morbidity and mortality. This prospective study aimed to evaluate the diagnostic and prognostic value of the novel biomarker presepsin (PSP) in episodes of FN in this specific cohort of patients. Methods: The study enrolled 37 patients with FN and 18 patients with neutropenia without fever as a control group. Patients with FN were divided into two groups: those with confirmed infections and those without them. Various clinical and laboratory parameters were analyzed, including inflammatory and biochemical markers, focusing on implications of PSP. Results: Among patients with FN, 65% had proven infections with significantly higher PSP levels compared to those without infections and control group (p < 0.001). Positive blood cultures were found in 13.5% of all FN episodes. PSP showed greater sensitivity than traditional biomarkers like procalcitonin and C-reactive protein for differentiating septic from non-septic complications. Increased PSP levels at admission suggested a poorer survival prognosis. Each 1 ng/mL increase in PSP correlated with a 5% increase in mortality risk (HR 1.05; p < 0.001), with a one-year mortality rate of 56.7%, underscoring the necessity for better predictive markers. Other markers, including CRP, PCT, IgG, and albumin, were not significantly associated with mortality; however, platelets and qSOFA exhibited borderline significance. Conclusions: PSP is a valuable biomarker for identifying high-risk FN in lymphoma patients and predicting mortality, correlating with infection severity. Larger multi-center studies are needed to validate these findings and optimize PSP’s clinical application to improve outcomes.

Background: Diffuse large B-cell lymphoma (DLBCL) is a biologically heterogeneous lymphoma with variable clinical outcomes despite established molecular and clinical prognostic models. Immunoglobulin G (IgG) N-glycosylation regulates antibody effector functions and reflects systemic immune status, but plasma IgG N-glycosylation has not previously been systematically investigated in DLBCL. We evaluated whether plasma IgG N-glycosylation is altered in DLBCL and examined its associations with molecular subtype, established prognostic indices, and clinical outcomes. Methods: Plasma samples were obtained from 54 treatment-naïve patients with pathologically confirmed DLBCL, not otherwise specified (NOS), and 54 age- and sex-matched healthy controls. IgG N-glycans were analyzed using capillary gel electrophoresis with laser-induced fluorescence (CGE-LIF), resolving 27 glycan peaks that were summarized into six derived glycosylation traits: agalactosylation (G0), monogalactosylation (G1), digalactosylation (G2), sialylation (S), bisecting N-acetylglucosamine (B), and core fucosylation (CF). Associations with disease status, cell-of-origin subtype, prognostic indices (International Prognostic Index (IPI), Age-Adjusted International Prognostic Index (aaIPI), revised International Prognostic Index (R-IPI), National Comprehensive Cancer Network International Prognostic index (NCCN-IPI), Central Nervous System International Prognostic Index (CNS-IPI) and inflammation-based cumulative prognostic score system (ICPS)) progression-free survival (PFS), overall survival (OS), and relapse were assessed using multivariable regression and Cox proportional hazards models adjusted for age and sex. Multiple testing was controlled using the Benjamini–Hochberg false discovery rate. Results: Compared with healthy controls, patients with DLBCL, NOS exhibited significantly increased agalactosylation and decreased digalactosylation and sialylation, consistent with a pro-inflammatory IgG glycosylation profile. The non-germinal center B-cell-like (non-GCB) subtype showed significantly lower monogalactosylation than germinal center B-cell like (GCB) DLBCL. Across multiple established prognostic indices, increasing clinical risk was consistently associated with increased agalactosylation and reduced digalactosylation. During follow-up, 20 patients (37%) relapsed, and 21 (39%) died. Increased agalactosylation was independently associated with shorter PFS, whereas reduced sialylation predicted both inferior PFS and an increased risk of relapse. Conclusions: Plasma IgG N-glycosylation is profoundly altered in DLBCL, NOS and is associated with molecular subtype, established prognostic indices, and clinically relevant outcomes. These findings identify plasma IgG N-glycosylation as a promising minimally invasive biomarker that reflects disease biology and provides prognostic information beyond conventional clinical risk models. Given the exploratory nature and modest size of this cohort, these findings should be considered hypothesis-generating and require validation in larger prospective cohorts.

Background/Objectives: Obinutuzumab was approved for front-line treatment of chronic lymphocytic leukemia in combination with chlorambucil pulses administered every 2 wks. Alternative schedules of chlorambucil enable the administration of higher total chlorambucil doses, and have better antileukemia activity. So far, evidence on the feasibility of combining obinutuzumab with alternative chlorambucil schedules is lacking. We performed this retrospective analysis to analyze real life outcomes in chronic lymphocytic leukemia patients receiving a combination of obinutuzumab with different chlorambucil schedules. Methods: This was a retrospective survey performed in order to analyze the feasibility and efficacy of different obinutuzumab and chlorambucil combinations in a real-life setting. Patients receiving this combination as a front-line therapy for chronic lymphocytic leukemia in participating centers, outside of clinical trials, in 2017 and 2018 were included. Results: Seventy-three patients fulfilling entry criteria were identified. Their median age was 76 years, and ranged from 58 to 90 years. The median follow up time was 59 months. The response rate was 89%, with a median progression-free survival time of 27 months, and an overall survival time of 49 months. Chlorambucil was administered as planned in 15 of the 22 (79%) patients treated with chlorambucil pulses every 2 weeks; in 15 of the 42 (34%) patients treated with 7-day courses of chlorambucil administered every 4 weeks; and in 0 of the 10 patients treated with a continuous high dose of chlorambucil (p = 0.002). Changes in treatment schedules were made due to side effects. The progression-free and overall survival rates were similar between the three groups. Conclusions: The combinations of obinutuzumab with more intensive chlorambucil schedules are less feasible, preventing the administration of the intended higher total dose of chlorambucil, and do not improve outcomes in comparison to chlorambucil pulses administered every 2 weeks.