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ABSTRACT The treatment landscape for relapsed/refractory follicular lymphoma (RR‐FL) is marked by a pivotal debate between chimeric antigen receptor T‐cell (CAR‐T) therapy and bispecific antibodies (BsAbs). While both CAR‐T therapy and BsAbs target similar immunobiology and molecular markers, their efficacy comparisons are hindered by the lack of direct clinical trial comparisons. Key trials, such as the ZUMA‐5 study, underscore axicabtagene ciloleucel (axi‐cel)'s efficacy in treating RR‐FL, achieving a 79% complete response rate with a median duration of response exceeding 3 years. Similarly, lisocabtagene maraleucel (liso‐cel) in the TRANSCEND FL study reports a 94% complete response rate, emphasizing robust outcomes in heavily pretreated patients. Among BsAbs, mosunetuzumab showed promise in the GO29781 trial, with a 62% overall response rate in heavily pretreated RR‐FL patients. Thus, CAR‐T therapy offers potential curative benefits with a single infusion. However, its efficacy is tempered by significant adverse events such as cytokine release syndrome (CRS), neurotoxicity, and cytopenias, requiring specialized management and patient monitoring. In contrast, BsAbs provide a more tolerable treatment option counterbalancing by lower response rates and frequent dosing requirements. Personalized treatment strategies are crucial because of these distinct efficacy and safety profiles. When considering cost‐effectiveness, both therapies need to be evaluated in the context of their clinical outcomes and quality of life improvements. Cost‐effectiveness considerations are essential; while CAR‐T therapies incur higher initial costs, their potential for long‐term remission may mitigate expenses associated with repeated treatments or hospitalizations. Future research into resistance mechanisms and optimal therapeutic sequencing will further refine RR‐FL management strategies. [ABSTRACT FROM AUTHOR]

Introduction: Myelofibrosis (MF) is a clonal hematological disorder characterized by bone marrow fibrosis, splenomegaly, and inflammatory cytokine dysregulation. While the role of steroids in MF is not fully defined, their anti-inflammatory properties may offer therapeutic benefits, particularly in managing anemia and other cytopenias. Steroids exert their effects by suppressing pro-inflammatory cytokines such as IL1, IL6, and TNF, and by enhancing anti-inflammatory cytokines like IL4 and IL10. Elevated levels of IL6 and other cytokines in MF are associated with anemia and poor prognosis, suggesting that steroid therapy could mitigate these effects. Areas covered: In this manuscript, we review clinical studies which evaluated the safety and efficacy of steroids in MF patients. Moreover, we examine clinical data of the combination of steroids with immunomodulatory agents and JAK inhibitors. Our literature search consisted of an extensive review of PubMed and clinicaltrials.gov. Expert opinion: The role of steroids in the management of MF remains poorly defined, though emerging evidence suggests a potential therapeutic benefit, particularly in managing anemia and other cytopenias. The combination with IMIDs has also yielded positive outcomes as demonstrated in several studies. Steroids may also play a crucial role in managing cytopenias in MF patients receiving JAKi. [ABSTRACT FROM AUTHOR]

Background: Malignant mesothelioma (MM) is a rare but lethal cancer strongly associated with asbestos exposure. This retrospective study examines mesothelioma trends and past asbestos exposure assessment in Emilia-Romagna, Northern Italy. Methods: Between 1996 and 2023, 3,513 cases of MM were recorded by the Regional Operating Center, predominantly in males (72%) and older than 65 years (79%). MM diagnosis was defined as certain, probable, and possible. Information concerning asbestos exposure was collected through an analytical questionnaire administered to patients or proxies and classified as occupational and non-occupational. Results: Occupational exposure accounted for 82% of cases, significantly increasing from 71% to 88% in the most recent period. A more accurate definition of occupational exposure indicates that specific exposure has gone from 49% in the first period to 62% and 58% in the last two periods; probable exposure decreased from 21% to 16%, while possible exposure decreased from 16% to 13%. Familiar exposure remained relatively constant at around 8%, environmental exposure slightly decreased from 4% to 2%, while non-occupational exposure remained stable at 2%. Among patients with exclusively occupational exposure (1,826 cases), 87% were male and aged between 65 and 75 years (36%) and 75+ (41%). Exposure rates for the province of residence see the province of Reggio Emilia with the highest occupational exposure rate (2.5 x 100,000 residents), followed by Ravenna (2.3 x 100,000 residents) and Parma and Piacenza, which have similar exposure rates with 2.2 x 100,000 residents. Occupational sectors such as construction, railway maintenance, and metalworking are identified as high-risk industries. Despite efforts to mitigate exposure, non-occupational and environmental exposures persist. The study highlights the importance of continuous surveillance and exposure monitoring to guide effective interventions and legal recognition of MM. [ABSTRACT FROM AUTHOR]

Simple Summary: COVID-19 has had a dramatic impact on new cancer diagnoses and the treatment of cancer patients. This study examines how the COVID-19 pandemic affected prostate cancer diagnosis, staging, and treatment in Reggio Emilia, Northern Italy. Using data from the Cancer Registry from 2018 to 2021, we found a significant drop in new prostate cancer diagnoses during 2020, the height of the pandemic. The number of new cases decreased by 31% in 2020, with a slight recovery of 5% in 2021. We also observed a shift towards more advanced stages and aggressive forms of prostate cancer, with fewer early-stage diagnoses and more cases of metastatic cancer. Despite these changes, treatments such as surgery and radiation therapy have remained constant. The pandemic disrupted an increasing trend of prostate cancer diagnoses seen before 2019, highlighting the need for ongoing diagnostic services and healthcare delivery, even during global health emergencies. Our study highlights the significant impact of COVID-19 on prostate cancer management and the importance of healthcare system resilience. The COVID-19 pandemic has caused delays in cancer diagnoses and reductions in treatments. The aim of this work is to evaluate the impact of the pandemic on prostate cancer by evaluating whether there has been a shift towards more aggressive (Gleason) and more advanced tumors (stage IV) and a decline in treatments. The study was conducted on 1123 cases of prostate cancer incident in the Province of Reggio Emilia, Northern Italy, in the period of 2018–2021. In 2020, there was a decline in new diagnoses of prostate cancer (−31%), followed by a slight recovery in 2021 (+5%). While Gleason 7 and 8–10 values remained constant, a significant decrease was recorded in stage I (38.7%, 41.6%, 35.5%, and 27.7%) and an increase in stage IV (13.1%, 13%, 15.4%, and 20%) cases in the years 2018, 2019, 2020, and 2021, respectively. However, there was no impact on surgical treatment (which remained constant at around 35%) and radiotherapy (around 39%). Our findings underline the profound impact of COVID-19 on prostate cancer management, highlighting the importance of healthcare resilience in the face of unprecedented disruptions. [ABSTRACT FROM AUTHOR]

Simple Summary: Colorectal cancer remains a prevalent neoplasm affecting both genders. Despite advancements in screening techniques facilitating early detection, effective patient management remains paramount. This study investigates the impact of a multidisciplinary team (MDT) approach on patient outcomes. Results reveal a significant improvement in survival rates among MDT-followed patients compared to those lacking MDT oversight. Notably, no-MDT patients exhibited a twofold increase in mortality risk from both colon and rectal cancers. Furthermore, advanced age (>70 years) and advanced-stage disease (III and IV) emerged as pivotal risk factors. Consequently, prioritizing MDT intervention for these high-risk cohorts is imperative to optimize therapeutic strategies. Colorectal cancer emerged as the third most prevalent malignancy worldwide, affecting nearly 2 million individuals in the year 2020. This study elucidates the pivotal role of a multidisciplinary team (MDT) in influencing the prognosis, as measured by relative survival rates, depending upon the stage and age. Cases recorded in an Italian Cancer Registry between 2017 and 2018 were included. Relative survival was reported at 1 and 3 years after diagnosis comparing MDT vs. no-MDT approaches. During the study period, 605 CRCs were recorded while 361 (59.7%) were taken care of by an MDT. Compared to no-MDT, MDT patients were younger with earlier stages and received more surgery. One year after diagnosis, survival was 78.7% (90% in MDT vs. 62% in no-MDT); stratifying by stage, in the MDT group there was no survival advantage for stage I (97.2% vs. 89.9%) and II (96.8% vs. 89.4%), but an advantage was observed for stage III (86.4% vs. 56.9%) and stage IV (63.7% vs. 27.4%). Similar values were observed at 3 years where a marked advantage was observed for stages III (69.9% vs. 35.1%) and IV (29.2% vs. 5.1%). The univariable analysis confirmed an excess risk in the no-MDT group (HR 2.6; 95% CI 2.0–3.3), also confirmed in the multivariable regression analysis (HR 2.0; 95% CI 1.5–2.5). Despite the increase in the number of MDT patients in 2018 (from 50% to 69%), this does not correspond to an improvement in outcome. [ABSTRACT FROM AUTHOR]

Myelodysplastic syndromes (MDS) encompass a heterogeneous set of acquired bone marrow neoplastic disorders characterized by ineffective hematopoiesis within one or more bone marrow lineages. Nearly half of MDS patients carry cytogenetic alterations, with del(5q) being the most prevalent. Since its first description, del(5q) was consistently correlated with a typical clinical phenotype marked by anemia, thrombocytosis, and a low risk of evolving into acute leukemia. Presently, the World Health Organization (WHO) classification of myeloid neoplasms recognizes a specific subtype of MDS known as "myelodysplastic neoplasm with low blast and isolated del(5q)" identified by the sole presence of 5q deletion or in combination with one other abnormality excluding −7/del(7q). Several studies have sought to unravel the biological processes triggered by del(5q) in the development of MDS, revealing the involvement of various genes localized in specific regions of chromosome 5 referred to as common deleted regions (CDR). This intricate biological landscape makes the MDS cells with del(5q) exceptionally sensitive to lenalidomide. Several studies have confirmed the efficacy of lenalidomide in this context. Regrettably, the response to lenalidomide is not conclusive, prompting ongoing research into biological mechanisms that drive patients toward leukemia and strategies to circumvent lenalidomide resistance and disease progression. [ABSTRACT FROM AUTHOR]

Multiple myeloma (MM) is an incurable neoplasm characterized by significant morbidity and mortality. Despite advances in treatment, MM patients eventually experienced a relapse of the disease. Penta‐drug refractory patients continue to be the hard core of relapsed/refractory (RR) settings. Teclistamab‐cqyv is a humanized IgG4 antibody and a bispecific BCMA‐director CD3 T‐cell engager. It recruits endogenous T cells, by targeting CD3 receptors expressed on their surface, resulting in their activation against BCMA, an antigen expressed by plasma cells. US Food and Drug Administration (FDA) and European Medicines Agency (EMA) have approved Teclistamab‐cqyv in monotherapy for the treatment of RRMM patients who have received at least three prior therapies, including immunomodulatory drugs (IMiDs), proteasome inhibitors (PIs), and anti‐CD38 monoclonal antibodies (MoAbs) and have demonstrated disease progression during the last therapy. Its effectiveness was demonstrated in a pivotal clinical trial where the overall response rate (ORR) reached 60%. Other clinical studies are currently ongoing to investigate the association of the bispecific antibody with novel drugs with encouraging preliminary results, especially in the setting of heavily pretreated patients. In this review, the authors will provide a comprehensive overview of the drug, including its mechanism of action, major clinical trials, and future perspectives. [ABSTRACT FROM AUTHOR]

Tagraxofusp (or SL‐401) is a recombinant molecule composed of human interleukin‐3 that binds CD123 on neoplastic cells fused to a truncated diphtheria toxin (DT). Tagraxofusp's most significant success has come from studies involving patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN), an aggressive disease that is usually refractory to conventional chemotherapy. Tagraxofusp had an acceptable safety profile and high efficacy in early phase I/II studies on patients with BPDCN. Another phase II study confirmed the good response rates, resulting in Food and Drugs Administration and European Medicine Agency approval of tagraxofusp for the treatment of BPDCN. Considering its high efficacy and its manageable safety profile, tagraxofusp has been suddenly explored in other myeloid malignancies with high expression of cell surface CD123, both in monotherapy or combination strategies. The triplet tagraxofusp‐azacytidine‐venetoclax appears to be of particular interest among these combinations. Furthermore, combination strategies may be used to overcome tagraxofusp resistance. The downregulation of DPH1 (diphthamide biosynthesis 1), the enzyme responsible for the conversion of histidine 715 on eEF2 to diphthamide, which is then the direct target of ADP ribosylation DT, is typically associated with this resistance phenomenon. It has been discovered that azacitidine can reverse DHP1 expression and restore sensitivity to tagraxofusp. In conclusion, the success of tagraxofusp in BPDCN paved the way for its application even in other CD123‐positive malignancies. Nowadays, several ongoing trials are exploring the use of tagraxofusp in different myeloid neoplasms. This review aims to summarize the actual role of tagraxofusp in BPDCN and other CD123‐positive myeloid malignancies. [ABSTRACT FROM AUTHOR]

This study aimed to assess the impact of a multidisciplinary team (MDT) approach on outcomes with endometrial cancer (EC) patients, utilizing 2013–2020 data from the Reggio Emilia Cancer Registry. Recurrence rate, treatments, and outcome indicators were compared between the MDT (319 cases) and non-MDT (324 cases) groups. Among 643 cases, 52.4% were over 65 years old, 98% had microscopic confirmation, and 73% were in stage I. Surgery was performed in 89%, with 41% receiving adjuvant therapies. Recurrence rates (10%) were similar between the two groups, but MDT patients who were older and predominantly in stage I exhibited 79% recurrence within one year (21% in the non-MDT group). Disease-free survival (DFS) showed no significant difference [HR 1.1; 95% CI 0.7–1.6], while differences in overall survival (OS) were notable [HR 1.5; 95% CI 1.0–2.4]. The 5-year OS rates were 87% and 79% in the MDT and non-MDT groups. Comparing the 2013–2015 to 2016–2020 study periods, a shift towards caring for older women, more advanced-stage patients, and those residing outside the metropolitan area, along with a greater number of relapsed cases (from 16% to 76%), were accounted for. These findings underscore the impact of an MDT on EC outcomes, highlighting the evolving patient demographics over time. [ABSTRACT FROM AUTHOR]