European Journal of Haematology最新文献

Objectives: To assess the effectiveness/safety of three proteasome inhibitors (PIs), plus lenalidomide-dexamethasone (Rd) triplet regimens, for the treatment of relapsed/refractory multiple myeloma (RRMM) in a real-world setting, using data from the observational INSIGHT-MM study (NCT02761187).

Methods: Adults with RRMM who received ixazomib, carfilzomib, or bortezomib plus Rd (IRd, KRd, or VRd, respectively) in the second or later line of therapy (LoT) were included. Patient characteristics, response to therapy (Kaplan-Meier analysis), and safety were reported descriptively. Multivariable Cox proportional hazards models were used to assess comparative effectiveness between regimens, whilst adjusting for cohort imbalances.

Results: Overall, 356 LoTs (IRd n = 181; KRd n = 96; VRd n = 79) from 348 patients were included. There was heterogeneity in patient characteristics between cohorts. Median real-world progression-free survival (rwPFS) for IRd, KRd, and VRd was 14.5, 13.2, and 9.1 months, respectively. After adjustment for baseline covariates, no significant differences in rwPFS were observed between regimens. All three regimens demonstrated a manageable safety profile.

Conclusions: IRd, KRd, and VRd demonstrated comparable effectiveness and safety for the treatment of RRMM in a real-world setting, highlighting the need for a holistic evaluation of individual patients' needs and circumstances when selecting an appropriate PI.

Clinical registration: Clinical trial registration for the INSIGHT-MM study: NCT02761187; https://clinicaltrials.gov/study/NCT02761187.

This is a plain language summary describing results from the Alfa-PROTECT study on safety and efficacy of damoctocog alfa pegol in previously treated children aged between 7 and 12 years with severe haemophilia A. Trial Registration: The Alfa-PROTECT trial is registered at ClinicalTrials.gov: NCT05147662.

PD-1 inhibitors have reshaped the treatment landscape of classical Hodgkin lymphoma, yet a substantial proportion of patients exhibit primary or acquired resistance driven by tumor-intrinsic alterations, immunosuppressive microenvironmental signals, metabolic constraints, and EBV-mediated modulation. This review summarizes key mechanisms underlying PD-1 resistance and highlights emerging biomarkers-including early ¹⁸F-FDG PET response, circulating tumor DNA kinetics, molecular subtyping, and spatial immune profiling-that enable early identification of nonresponders and support precision immunotherapy. Novel therapeutic strategies such as macrophage-targeted agents, metabolic modulators, bispecific antibodies, low-dose PD-1 regimens, and CD30-directed CAR-T cells show promise in overcoming resistance, particularly when integrated into adaptive, biomarker-guided treatment algorithms. Early incorporation of PET and ctDNA monitoring may inform timely treatment adaptation, while combination approaches addressing macrophage-driven suppression or redundant immune checkpoints should be considered in biologically high-risk patients. Overall, a deeper mechanistic understanding coupled with biomarker-driven stratification is essential to optimize PD-1-based therapy and improve long-term outcomes in cHL.

As the landscape of treatments for sickle cell disease (SCD) shifts, relatively little is known regarding the rates of medication prescription for SCD at a population level. This study was a cross-sectional annualized cohort analysis that used North Carolina Medicaid claims data from 2018 through 2022 to examine rates of prescription of FDA-approved medications for SCD and factors associated with their use. Adults with SCD were identified using a standard administrative data algorithm, and their data were aggregated to the person-year level. Annual prescription rates (≥ 1 claim) of hydroxyurea, L-glutamine, voxelotor, crizanlizumab, and opioid analgesics were calculated over time, and binomial mixed effects models examined associations between prescription and individual characteristics. Among 1733 individuals, the rate of hydroxyurea prescription ranged from 24.2%-26.7%. Rates for L-glutamine, voxelotor, and crizanlizumab were less than 6.0% each year. The rate of opioid prescription ranged from 51.4%-53.9%. Seeing a hematologist was consistently associated with higher odds of receiving SCD-specific medications. Age was associated with decreased prescription of hydroxyurea, L-glutamine, and opioids, but increased prescription of voxelotor. Males had higher odds of receiving hydroxyurea. Although use of FDA-approved medications for SCD was low, improved access to hematologists may increase medication utilization.

Objectives: Azacitidine (AZA) combined with venetoclax (VEN) as an outpatient treatment of unfit patients with acute myeloid leukemia (AML) has been infrequently investigated.

Methods: We report on 65 elderly AML patients: 35 patients received AZA + VEN as first-line and 30 after progression on prior treatment with AZA (R/R group). Thirty-eight patients were treated as outpatients, while 27 were hospitalized. The overall survival (OS) and event-free survival (EFS) were calculated, and predictive factors were assessed using Cox regression models.

Results: Inpatients were slightly younger, with a median age of 72 versus 74 years in outpatients (p = 0.015). Median WBC was higher in inpatients (median 7.3 × 10⁹/L vs. 2.9 × 10⁹/L, p = 0.020). Median marrow blast count was 43% in inpatients versus 25.5% in outpatients (p = 0.042). Treatment setting emerged as a key predictive factor for infection development during Cycle 1 in both univariate (p = 0.016) and multivariate analysis (p = 0.043), in the overall cohort. Inpatients had a significantly higher infection rate (81.4%) versus outpatients (44.7%, p = 0.004). In R/R group, 1-year EFS was 68% for outpatients versus 38% for inpatients (p = 0.009). One-year OS was 77% in outpatients versus 38% in inpatients (p = 0.052).

Conclusions: In most instances, outpatient administration of Cycle 1 of AZA + VEN should be preferred as a beneficial option.

Allogeneic hematopoietic stem cell transplantation (HSCT) is increasingly used to treat malignant and non-malignant diseases. Following allogeneic HSCT, patients are particularly vulnerable to vaccine-preventable diseases (VPD) because conditioning depletes immune cells, including memory cells. Revaccination is therefore essential, but multiple factors, such as conditioning regimen, stem cell source, HLA compatibility, graft-versus-host-disease (GVHD), and age, affect immune reconstitution and vaccine response. Current guidelines recommend uniform vaccination schedule for all allogeneic HSCT patients, despite this heterogeneity. In this review, we discuss how these factors influence immune reconstitution and vaccine response, and highlights the need for a more individualized approach. Based on current evidence, we propose that vaccine timing, particularly for inactivated vaccines, could benefit from adjustment according to immune recovery markers, such as lymphocyte counts and presence of GVHD, rather than relying on fixed post-HSCT timepoints. We also discuss emerging immunotherapies, including CAR-T cells and bispecific antibodies, which can induce similarly prolonged immunosuppression and may benefit from personalized vaccination strategies. Further studies in pediatric populations are needed to define immunological threshold that would enable safer and more effective personalized vaccination schedules.

Cold agglutinin disease (CAD) is a low-grade lymphoproliferative disorder accounting for 15%-30% of patients suffering from autoimmune hemolytic anemias. The clonal B cells produce autoantibodies primarily of the IgM-κ class that cause agglutination of red blood cells (RBCs) at temperatures ≤ 37°C and activate the classical complement pathway with subsequent RBC destruction. Before the approval of the monoclonal antibody sutimlimab, treatment options were limited. Sutimlimab inhibits the classical complement pathway at C1s while sparing the lectin and alternative complement pathways. Efficacy, safety and tolerability of sutimlimab have been established in the multicenter CARDINAL and CADENZA trials. In the present investigation, 10 patients on sutimlimab were followed up to 96 weeks in the Managed Access Program (MAP) in Essen. Eight of these patients had previously participated in the multicenter trials and were restarted on sutimlimab after a median washout period of 12.6 weeks. In addition, two sutimlimab-naive patients were included. Hemoglobin concentration increased in all patients (median hemoglobin concentration before therapy 9.8 vs. 12.5 g/dL at the end of the study). Bilirubin levels normalized already after 2 weeks in all patients. Reticulocyte count declined in nine, haptoglobin and hemopexin concentrations normalized in six and 10 patients, respectively. In conclusion, the present investigation with primary CAD patients in a single center demonstrates long-term normalization of laboratory parameters, abrogation of specific clinical symptoms and absence of drug-related side effects with sutimlimab.

Endothelial cells play a complex role in lymphoma by becoming genetically abnormal alongside tumor cells, forming blood vessels that fuel lymphoma growth and invasiveness, and contributing to the establishment of an immunosuppressive tumor microenvironment. Because of their significant role in lymphoma growth and immune evasion, endothelial cells and the processes that regulate them are being explored as attractive targets for new anti-angiogenic therapies and immunotherapies to overcome the limitations of anti-angiogenic therapy in lymphoma treatment.

This retrospective study evaluates the efficacy and safety of donor lymphocyte infusion (DLI) after allogeneic hematopoietic stem cell transplantation (HSCT) in children. We describe the long-term use of preemptive, prophylactic, and therapeutic DLI with a gradual dose increase in half-log increments. Under close monitoring, we increased the DLI dose only in patients that did not show signs of graft-versus-host disease (GVHD). In the preemptive cohort, 10 of 12 patients (83%) with minimal residual disease (MRD) positivity remained relapse-free. Among 11 patients with genetic diseases and mixed chimerism, nine (82%) responded to preemptive DLI. Six patients (100%) of the prophylactic cohort with a very high risk of relapse had a successful outcome without relapse or GVHD. Three of the five patients (60%) of the therapeutic cohort were successfully treated with DLI. We observed acute GVHD (grade I and II) in only two patients (6%). The results of our study indicate that the long-term use of DLI is a promising strategy and can effectively prevent relapse, graft rejection, and even cure relapse. The observed low rate of GVHD may be attributed to the gradual dose increase. Therefore, we consider DLI a safe and effective therapeutic option.

Background: Epstein-Barr virus-positive post-transplant lymphoproliferative disorder (EBV + PTLD) is a serious complication after allogeneic hematopoietic stem cell transplantation (allo-SCT). Given evolving transplantation practices, updated data are needed.

Objective: Multicenter analysis of PTLD epidemiology, clinical characteristics, and outcomes in Spain.

Methods: Retrospective study across 17 Spanish transplant centers including all proven/probable EBV+ PTLD cases after allo-SCT from January 2000 to June 2023.

Results: Among 14.568 allo-SCTs, 170 PTLD cases were identified (1.2%) peaking in 2010-2017 (2.0%), versus 0.9% in 2000-2009 and 0.7% in 2018-2023. Median onset was 91 days; 75% occurred within 6 months. Proven cases comprised 67%, mostly diffuse large B-cell lymphoma. Advanced stage occurred in 67%, extranodal disease in 22%. Rituximab ± immunosuppression reduction (ISR) was given to 80%, yielding a 62.4% response rate. Responders had superior survival (2-year OS 73.4% vs. 10.7%). EBV-specific cellular therapies were infrequently used. Median follow-up was 97.8 months; 5-year OS 39.6%, with PTLD causing 49% of deaths. Severe hypoalbuminemia, lack of ISR, and rituximab refractoriness predicted worse survival.

Conclusions: EBV + PTLD frequency has declined in Spain. Prognosis remains poor for rituximab non-responders, highlighting limited access to EBV-specific cellular therapies as an unmet need.