Hematological Oncology最新文献

Diffuse large B-cell lymphoma (DLBCL) is the most common B-cell non-Hodgkin lymphoma in the world. Treatment options for relapsed DLBCL in the third line and beyond include chimeric antigen receptor T-cell therapy, T-cell–engaging bispecific antibodies, and loncastuximab tesirine (loncastuximab tesirine-lpyl [Lonca]), each with unique toxicity profiles. There is still an unmet need for guidance on managing Lonca-associated adverse events (AEs), particularly for oncologists who have limited experience with this antibody–drug conjugate. Here, an online survey among lymphoma specialists in the US between June and August 2024 assessed practice patterns and experiences, including Lonca treatment patterns, AE management, patient concerns, and physician perceptions. Based on these responses, an algorithm was developed to help manage Lonca-associated AEs. The most commonly reported AEs were edema and rash/photosensitivity, typically occurring within the first 4 doses, whereas fatigue was the most common patient concern. Lonca-associated AEs were managed by delaying or discontinuing Lonca or by prescribing diuretics, steroids, or antihistamines, depending on the AE observed. The survey results align with findings from prior clinical trials and support the manageability of Lonca-associated AEs in a wide variety of settings. The included algorithm provides guidance for managing AEs, such as edema, myelosuppression, and cutaneous reactions.

Infections often complicate pediatric-inspired treatments for adult Philadelphia-negative acute lymphoblastic leukemia (Ph- ALL). Literature data on these complications are difficult to interpret due to the heterogeneity of types of infections analyzed or patients and treatment characteristics. A deeper insight on the infections occurring in the real life in uniformly treated ALL patients is lacking. This study investigated infectious complications in 240 newly diagnosed adult Ph- ALL patients treated in the real life according to the GIMEMA LAL1913 protocol by 18 Italian centers participating in the Campus ALL network. Incidence, etiology of microbiologically documented infections and invasive fungal infections (IFI) and mortality for infection were determined. Potential risk factors and the prophylactic strategies used during the first chemotherapy course (C1) were analyzed. Of 240 patients, 145 (60%) experienced at least one infectious episode, with bacterial infections being the most common (74.3%), followed by viral (13.9%), fungal (10.1%), and Pneumocystis jirovecii (1.7%) infections. The blood stream was the most involved site, pneumonia occurred in 14.6% of cases, half of which being fungal. Infections were prevalent during C1, affecting 40.5% of patients; IFI occurred in 12.5% of patients, most of them in C1. Risk factors for infections included older age (≥ 55 years and particularly > 65 years) and comorbidities only for IFI. The mortality rate for infection was 3.3%. Antibacterial, antiviral, antifungal, and anti-PJ prophylaxis were variably administered and did not associate with a significant reduced infection rate. In conclusion, the rate of infectious complications in the real life of adult Ph- ALL patients treated with a pediatric-inspired intensive regimen is high, mainly during induction and mostly bacterial, particularly in the bloodstream, with a high IFI rate. Older age, mainly over 65 years, is a risk factor for all types of infection. The antimicrobial prophylaxis was not associated to a reduced risk of infection.

Relapsed/refractory multiple myeloma (RRMM) patients with dialysis-dependent renal impairment face limited therapeutic options due to exclusion from clinical trials, a lack of evidence-based guidelines, and inferior outcomes. Bispecific antibodies targeting B-cell maturation antigen (BCMA) have shown promise in RRMM treatment but remain understudied in this vulnerable population. To illustrate this issue, we introduce the case of a 68-year-old female with triple-class RRMM and end-stage renal disease requiring hemodialysis, treated with elranatamab as a second line treatment following progression after therapy with daratumumab, bortezomib, lenalidomide, and dexamethasone. Despite experiencing grade I cytokine release syndrome during the initial administrations, symptoms were managed effectively with tocilizumab and dexamethasone, allowing treatment continuation. The patient achieved a very good partial remission within 7 weeks. Although hemodialysis dependence persisted, the therapy was well-tolerated with manageable adverse events. According to the literature, BCMA-directed immunotherapies, including teclistamab, belantamab mafodotin, and idecabtagene vicleucel, have shown efficacy in dialysis-dependent RRMM patients, though data remain limited. Pharmacokinetic analyses indicate that mild or moderate renal impairment does not have a significant impact on the pharmacokinetics of elranatamab. Although no retrospective studies or case series have investigated the use of elranatamab in dialysis-dependent patients, a single case report suggests that its administration is both feasible and well-tolerated in this population despite the absence of comprehensive pharmacokinetic data. This review highlights feasibility, safety, and encouraging efficacy of elranatamab in managing RRMM in a dialysis-dependent patient, representing the second case report in the literature. By providing real-world evidence for the use of bispecific antibodies in end stage renal disease patients, this review emphasizes the potential for expanding therapeutic options to this vulnerable population while highlighting the need for vigilant monitoring of infection prevention and management. Prospective studies are warranted to validate these findings and optimize therapeutic strategies for patients with RRMM and severe renal impairment.

Diffuse large B cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma. Tripartite motif containing 44 (TRIM44) belonging to the TRIM family, is involved in tumor development and is highly expressed in a variety of tumors. However, the role of TRIM44 in DLBCL remains undefined. Gain and loss-of-function studies were performed on lymphoblast cell lines DB and SU-DHL-4 to investigate its function. TRIM44 overexpression significantly promoted cell proliferation and viability, whereas its silencing inhibited proliferation and induced apoptosis. TRIM44 overexpression upregulated the LC3II/LC3-I ratio and Beclin1 expression, as well as increased autophagosomes formation, suggesting autophagy activation. Notably, TRIM44 conferred chemoresistance to doxorubicin in DB cells by increasing autophagic activity. In vivo study on mice revealed that TRIM44 overexpression increased Ki67 and PCNA expression, suggesting an increased tumor growth. Our previous work revealed that miR-665 is a tumor suppressor in DLBCL. The results of miRNA pull-down and luciferase reporter assay indicated that TRIM44 was a direct target of miR-665. In conclusion, TRIM44 promoted DLBCL progression by increasing autophagy-mediated chemoresistance, revealing the involvement of miR-665/TRIM44 axis.

Primary mediastinal large B-cell lymphoma (PMBL) is a rare entity that predominantly affects young female patients and typically presents as a large and compressive anterior mediastinal mass. Accumulating evidence suggests relationships among PMBL patient body composition (BC), cancer outcomes, and treatment-related toxicities. The aim of this study was to evaluate the impact of BC on PMBL patients using PET-CT images acquired pretreatment. Two hundred nineteen patients were included in an ancillary analysis of a multicenter retrospective LYSA cohort of treatment-naïve adult PMBL patients who received first-line treatment with ACVBP, CHOP14 or CHOP21 plus anti-CD20. Anthropometric parameters were assessed from the baseline PET-CT image using two methods: (i) manual segmentation at the L3 level and (ii) automatic software-based multislice measurements with Anthropometer3DNet. The median age was 35.4 years (range 18–88 years), and the median body mass index was 23.8 kg/m² (15.6; 40.8). Overall, 137 patients were treated with R-ACVBP, 44 received R-CHOP14, and 38 were treated with R-CHOP21. Patients with low lean body mass had a higher incidence of febrile neutropenia, both in the overall cohort (25% vs. 12.6%, p = 0.02) and in the R-ACVBP subgroup (35.7% vs. 19.4%, p = 0.03). Univariate analysis showed that in patients treated with R-ACVBP, subcutaneous low adiposity, determined by 3D measurements, was associated with overall survival (OS) (p = 0.04). At 3 years, the OS (95% CI) was 96% (93–100) in above-median adiposity patients and 86% (78–95) in below-median adiposity patients. Low lean body mass (LBM), assessed from the pretreatment PET-CT images using automatic Anthropometer3DNet software, may serve as a predictive marker for acute treatment-related toxicity in PMBL patients, particularly those receiving the dose-intensive R-ACVBP regimen. Additionally, depletion of the subcutaneous fat mass was correlated with an increased risk of mortality, highlighting the importance of a comprehensive BC assessment in this patient population.