Search Results (53)

T-cell-engaging antibodies are a promising new type of treatment for patients with refractory or relapsed (R/R) diffuse large B-cell lymphoma, which has changed the prognosis and evolution of these patients in clinical trials. Bispecific antibodies (BsAbs) bind to two different targets (B and T lymphocytes) at the same time and in this way mimic the action of CAR (chimeric antigen receptor) T-cells. They are the T-cell-engaging antibodies most used in practice and are a solution for patients who do not respond to second- or later-line therapies, including chemoimmunotherapy, followed by salvage chemotherapy and hematopoietic stem cell transplantation. They are a therapeutic option for patients who are ineligible for CAR T-cell therapy and are also active in those with prior exposure to CAR T-cell treatment. A remarkable advantage of BsAbs is their rapid availability, even if the disease progresses rapidly, unlike CAR T-cell treatment, and they avoid the practical and financial challenges raised by autologous CAR T-cell therapies. CAR-T has been proven to have better efficacy compared to BsAbs, but cytokine release syndrome and neurotoxicity have appeared significantly more frequently in patients treated with CAR T-cells. The possibility of combining BsAbs with chemotherapy and their administration for relapses or as a frontline therapy is being studied to increase their efficacy. BsAbs are a life-saving therapy for many patients with diffuse large B-cell malignant non-Hodgkin’s lymphoma (NHL) who have a poor prognosis with classical therapies, but are not without adverse effects and require careful monitoring. Full article

Primary plasma cell leukemia (pPCL) is a rare and aggressive plasma cell dyscrasia. According to revised diagnostic criteria, pPCL is defined by the presence of ≥5% circulating plasma cells (CPCs) in the peripheral blood of patients with newly diagnosed multiple myeloma (NDMM). pPCL is characterized by a distinct cytogenetic profile, including frequent t(11;14), MAF/MAB translocations, 1q gain, and del(17p). While t(11;14) is generally associated with a favorable prognosis, the coexistence of multiple high-risk cytogenetic abnormalities is linked to poorer outcomes. Tandem autologous hematopoietic stem cell transplantation and novel anti-myeloma agents have improved survival in some patients; however, overall prognosis remains poor, particularly in those ineligible for transplantation. Venetoclax and emerging immunotherapies, such as CAR-T cells and bispecific antibodies, show promise and merit clinical trials focused on pPCL-enriched cohorts. Additionally, recent findings associating even minimal CPCs with adverse outcomes in NDMM support broader inclusion criteria in future trials. A deeper understanding of pPCL’s molecular pathology is critical for the development of effective targeted therapies. This article reviews recent advances in the molecular understanding of and treatment strategies for pPCL. Full article

Background/Objectives: Bendamustine (BEN) combined with rituximab (RTX) remains a standard first-line therapy for transplant-ineligible patients with newly diagnosed mantle cell lymphoma (MCL). Meanwhile, novel targeted therapies such as Bruton tyrosine kinase inhibitors (BTKis) are increasingly used in the treatment of relapsed/refractory (R/R) MCL. We recently reported that a novel oral formulation of BEN exhibits comparable efficacy to the intravenous counterpart. In this study, we investigated the efficacy of oral BEN administered alone or in combination with the oral BCL-2 inhibitor Venetoclax (VEN) and/or the oral BTKi Acalabrutinib (ACAL), against two human MCL cell lines (Jeko-1 and Z-138) representative of the R/R disease subtype. Methods: We performed in vitro analyses using MTS viability and Annexin V/PI apoptosis assays. For the in vivo studies, all treatments were administered via oral gavage in xenograft mouse models. Therapeutic efficacy was evaluated by monitoring tumor growth and survival. Results: BEN induced significant cytotoxicity in both cell lines at low, clinically relevant concentrations. In contrast, VEN demonstrated limited efficacy as monotherapy, with Z-138 showing sensitivity only at high doses. However, combining BEN with VEN with or without ACAL, enhanced apoptosis and cytotoxicity, with more pronounced effects in Z-138. In vivo, oral BEN significantly reduced tumor growth and prolonged survival in both xenograft models. In the Z-138 model, the addition of VEN ± ACAL further improved survival outcomes. Conclusions: Our findings support the efficacy of oral BEN as both a monotherapy and as part of an all-oral treatment regimen for MCL. These results warrant further investigation into the clinical potential of oral BEN, particularly in combination with targeted agents. Full article

Hepatocellular carcinoma (HCC) is a commonly diagnosed malignancy, with the treatment for transplant-ineligible localized disease traditionally relying on locoregional therapies, such as surgical resection, transarterial chemoembolization (TACE), and transarterial radioembolization (TARE). Systemic therapy has historically been reserved for advanced, unresectable HCC. However, lenvatinib, an oral multikinase inhibitor, has recently gained traction as part of a multimodal approach for localized HCC in combination with locoregional treatments. An upfront TACE or TARE can induce tumor hypoxia, leading to the upregulation of hypoxia-inducible factor-1 alpha (HIF-1α) and vascular endothelial growth factor (VEGF), which promotes tumor angiogenesis and progression. The rationale for combining lenvatinib with a locoregional therapy is to enhance tumor shrinkage while preserving liver function before a definitive intervention. Clinical trials, such as TACTICS and LAUNCH, have demonstrated improved outcomes with this approach. Additionally, retrospective studies, including those incorporating immune checkpoint inhibitors, have reported further benefits. This review explores the combination of lenvatinib with various locoregional modalities, including TARE, microwave ablation (MWA), and radiofrequency ablation (RFA), highlighting their indications and clinical outcomes. Furthermore, we discuss the ongoing and upcoming clinical trials investigating the integration of systemic agents with locoregional therapies for intermediate-stage HCC, including EMERALD-1, EMERALD-3, LEAP-012, and CheckMate 74W. Full article

Background: Acute myeloid leukemia (AML) primarily affects older adults and is associated with poor prognosis, particularly in patients aged ≥ 60 years with comorbidities and adverse disease characteristics. Standard intensive chemotherapy, such as the “7 + 3” regimen, has shown limited efficacy and substantial toxicity in this population, underscoring the need for alternative treatment strategies. In recent years, venetoclax-based regimens have emerged as an important option, demonstrating promising outcomes in elderly patients traditionally considered unfit for intensive therapy and, more recently, even in selected fit patients. Methods: This narrative review provides a comprehensive comparative analysis of intensive chemotherapy and venetoclax-based regimens in elderly AML patients. This review synthesizes evidence from prospective and retrospective clinical trials, with focuses on treatment efficacy, safety, and the ability to bridge patients to curative allogeneic hematopoietic stem cell transplantation (allo-HSCT). Results: Intensive chemotherapy has achieved complete remission (CR) rates of 40–60% in elderly AML patients, though the median overall survival (OS) rarely exceeds 12 months. Conversely, venetoclax combined with hypomethylating agents has recently demonstrated CR rates of up to 74%, with 83% of responders proceeding to allo-HSCT in selected studies. Venetoclax-based regimens have also been associated with improved tolerability and reduced treatment-related mortality. Discussion: This review highlights a paradigm shift in the management of AML in the elderly. While intensive chemotherapy remains a standard option for selected patients, the increasing use of venetoclax-based regimens represents a novel and effective strategy with the potential to overcome traditional limitations, especially in patients previously deemed ineligible for curative approaches. The high remission and transplantation rates observed with non-intensive therapies support their role not only as a palliative alternative but as a bridge to cure. Conclusions: Venetoclax-based regimens are reshaping the treatment landscape of AML in the elderly, offering high response rates and facilitating access to allo-HSCT. Further research is needed to optimize treatment sequencing, explore novel combinations, and reduce relapse rates after transplants, ultimately improving the long-term outcomes in this high-risk population. Full article

Advanced heart failure (AHF) represents the terminal stage of heart failure (HF), characterized by persistent symptoms and functional limitations despite optimal guideline-directed medical therapy (GDMT). This review explores the clinical definition, pathophysiology, and therapeutic approaches for AHF. Characterized by severe symptoms, New York Heart Association (NYHA) class III-IV, significant cardiac dysfunction, and frequent hospitalizations, AHF presents substantial challenges in prognosis and management. Pathophysiological mechanisms include neurohormonal activation, ventricular remodeling, and systemic inflammation, leading to reduced cardiac output and organ dysfunction. Therapeutic strategies for AHF involve a multidisciplinary approach, including pharmacological treatments, device-based interventions like ventricular assisted devices, and advanced options such as heart transplantation. Despite progress, AHF management faces limitations, including disparities in access to care and the need for personalized approaches. Novel therapies, artificial intelligence, and remote monitoring technologies offer future opportunities to improve outcomes. Palliative care, which focuses on symptom relief and quality of life, remains crucial for patients ineligible for invasive interventions. Early identification and timely intervention are pivotal for enhancing survival and functional outcomes in this vulnerable population. This review underscores the necessity of integrating innovative technologies, personalized medicine, and robust palliative strategies into AHF management to address its high morbidity and mortality. Full article

Introduction: Patients with transplant-ineligible (TIE) multiple myeloma (MM) have high rates of symptom burden. The aim of this study was to develop and validate a prognostic model to predict symptoms in patients with TIE MM. Methods: In this population-based, retrospective cohort study, using multiple administrative health care databases linked using a unique encrypted patient identifier in Ontario, Canada, symptoms were identified using the patient self-reported Edmonton Symptom Assessment System (ESAS) at each clinic visit. The primary outcome was the presence of moderate-to-severe (ESAS score 4–10) symptoms (specifically symptoms of pain, tiredness, depression, and impaired well-being) within one year from the index date. Using the entire cohort, a multivariable logistic regression model with baseline covariates was developed to predict the risk of experiencing each of the above symptoms, categorized as moderate to severe within 1 year post-index date. Internal validation of the model was assessed via bootstrap validation methods. Results: A total of 1535 TIE adults with MM met the inclusion criteria. The median age was 75, with 25.2% of patients aged 80 years or older. In the multivariate analysis, baseline symptoms continued to be most associated with future symptom burden. Baseline severe pain (OR 9.84, 95% CI 6.29–15.7) was most associated with patients experiencing moderate–severe pain one year post-index date. Similarly, baseline severe tiredness (OR 17.34, 95% CI 9.00–33.42), baseline severe depression (OR 28.07, 95% CI 15.96–49.38), and baseline severely impaired well-being (OR 4.12, 95% CI 2.30–7.37) were the biggest predictors of patients experiencing moderate–severe tiredness, depression, and impaired well-being, respectively, at one year after the index date. Conclusions: Patients with MM experience persisting symptoms of pain, tiredness, depression, and impaired well-being, with baseline symptoms being the biggest predictor of future symptom burden. Full article

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) has surged as a major cause of liver transplants in the United States. Existing studies have presented conflicting findings regarding the association between liver characteristics (specifically steatosis and fibrosis) and mortality. This study investigates the relationship between the controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) via vibration-controlled transient elastography (VCTE) and all-cause mortality in MASLD patients. Methods: Using the NHANES 2017-2018 database, 3821 individuals representing the United States population with MASLD underwent VCTE for liver stiffness measurement. Exclusion criteria were applied, eliminating ineligible cases, incomplete examinations, underage individuals, and those with hepatitis B or C, along with significant alcohol consumption history. Cox proportional hazard models assessed the hazard ratio (HR) for all-cause mortality in CAP and LSM. Cox regression analysis with interaction terms was employed for deeper exploration. Results: The study unveiled a strong, independent correlation between LSM and all-cause mortality. However, the CAP failed to demonstrate a significant association with mortality in both univariate and adjusted analyses, contrary to recent findings. The analysis underscores the importance of accurately measuring liver stiffness via VCTE in predicting adverse outcomes in MASLD patients, emphasizing the pivotal role of fibrosis in assessing mortality risk. Conclusion: This study reaffirms the robust link between liver fibrosis (measured through VCTE) and mortality among MASLD individuals. The absence of a significant association between steatosis (indicated by CAP) and mortality challenges recent research, urging further comprehensive investigations with larger cohorts to delineate steatosis’ precise impact on MASLD-related mortality. Full article

Background/Objectives: Vaccine hesitancy among immunocompromised patients is complex and not well understood. This study aimed to determine the rate of COVID-19 vaccine hesitancy among pediatric oncology and bone marrow transplant (BMT) patients and to understand associated factors. Methods: Parents of patients (≤18 years) with cancer or post-BMT completed the Parent Attitudes about Childhood Vaccines Survey. A COVID-19 vaccine hesitancy score (VHS-COVID) was calculated from 0 to 100 (higher scores indicating increasing hesitancy). A small group of patients (patients older than 15 years) were also surveyed directly. Results: Among 113 parent respondents, the majority were female (58%) and at least college/university educated (78%). The majority (73%) of patients had cancer (61% leukemia/lymphoma, 37% solid/CNS tumors), while 27% had received BMT for malignant and non-malignant conditions. Only 48% of patients had been vaccinated against COVID-19, compared to 88% of parents. Ineligibility due to phase of cancer/BMT treatment (27%), vaccine hesitancy (24%), and age (24%) were the top three reasons for not vaccinating against COVID-19. Only 13% of parents said they would “definitely vaccinate” if their child became eligible. VHS-COVID scores were higher for parents of patients in surveillance versus active therapy (mean 61 vs. 48; p = 0.03). Parents who had received fewer COVID-19 vaccine doses (0–1 vs. ≥2) were more hesitant toward all vaccines (p = 0.0002), COVID-19 vaccines (p = 0.0003), and influenza vaccines (p = 0.005). Conclusions: Vaccine hesitancy is common among this population and was demonstrated through beliefs (hesitancy scores) as well as vaccine uptake. Future work should focus on education targeting vaccine eligibility and engaging with vaccine hesitant families in the immunocompromised community. Full article

Background: The development of newer agents, including anti-CD38 monoclonal antibodies (mAbs), has significantly improved overall survival (OS) in patients with relapsed or refractory multiple myeloma (RRMM). However, the treatment of older patients with RRMM who are transplant-ineligible remains challenging. Methods: We retrospectively evaluated OS in 78 transplant-ineligible patients with RRMM who were aged ≥ 65 years and treated at our institution between February 2012 and November 2023. Results: Unadjusted OS was significantly longer in the anti-CD38 mAb-exposed group (i.e., those previously treated with daratumumab and receiving isatuximab plus pomalidomide and low-dose dexamethasone because of disease progression during treatment with daratumumab [n = 6], daratumumab plus pomalidomide and low-dose dexamethasone [n = 9], or isatuximab plus pomalidomide and low-dose dexamethasone without daratumumab-exposure [n = 14]) than in the anti-CD38 mAb-naïve group (no exposure to daratumumab or isatuximab [n = 49]) (p < 0.001). To address potential confounder factors associated with use or nonuse of anti-CD38 mAbs, we performed propensity score matching (PSM) using age, sex, performance status, and Geriatric 8 and Instrumental Activities of Daily Living scores. PSM identified 14 subjects from the anti-CD38 mAb-exposed group with baseline characteristics similar to those of 14 subjects from the anti-CD38 mAb-naïve group. After PSM, the adjusted OS was significantly longer in the anti-CD38 mAb-exposed group than in the anti-CD38 mAb-naïve group (p < 0.001). Conclusion: These findings provide insights into the optimal use of anti-CD38 mAbs in patients with RRMM who are transplant-ineligible and aged ≥65 years and on candidates who are appropriate for novel approaches, such as chimeric antigen receptor T-cell or bispecific T-cell engager therapy. Full article

Introduction: A combination of elotuzumab, pomalidomide, and dexamethasone (EPd) was approved for the treatment of relapsed/refractory multiple myeloma (RRMM) following the ELOQUENT-3 phase II clinical trial. However, the clinical experience with this therapy is still limited. In this retrospective study, we analyzed the efficacy and safety of EPd in a real-world cohort of RRMM patients. Patients and Methods: The medical records of 22 patients who received EPd for RRMM at Yokohama Municipal Citizen’s Hospital (Japan) between January 2020 and July 2021 were reviewed. Results: The median age of our cohort was 73.5 years. The overall response rate was 55%. With a median follow-up of 20.2 months, the median progression-free survival (PFS) was 9.1 months (95% confidence interval [CI], 2.5–23.0 months). The median PFS was shorter in patients with a poor performance status (PS) than in those with favorable PS (2.5 vs. 10.8 months; p < 0.01). Patients with prior daratumumab had significantly shorter PFS than those without prior daratumumab (2.1 vs. 23.0 months; p < 0.01). Additionally, patients with prior pomalidomide had significantly shorter PFS (1.7 vs. 10.3 months; p < 0.01). In the multivariate analysis, poor PS (hazard ratio [HR] = 4.1, 95% CI: 1.1–15.6; p = 0.04) and prior exposure to daratumumab (HR = 3.8, 95% CI: 1.1–13.8; p = 0.04) remained significantly associated with shorter PFS. Conclusions: The results of our study suggest that EPd is an active and well-tolerated regimen in RRMM, even in real-world patients. Furthermore, EPd may be useful, especially in daratumumab-naïve patients. Full article

Real-world evidence on the impact of monoclonal antibodies as first-line treatment in Spain is limited. This observational, retrospective and prospective, multicenter, descriptive study included 117 transplant-ineligible newly diagnosed multiple myeloma (TIE-NDMM) patients divided into Group A, who received no daratumumab standard regimens, and the DVMP group (daratumumab, bortezomib, melphalan, and prednisone treatment). More than 90% of the patients in Group A received bortezomib, lenalidomide, or a combination of them. The median follow-up time for Group A was 38.2 months in comparison to 25.8 months for the DVMP group (p < 0.0001). The rate of DVMP patients that experienced disease progression or death from any cause was 36.8%, compared to 67.3% of Group A patients at 36 months of follow-up. The DVMP group had a higher 36-month progression-free survival (PFS) rate (52.9% vs. 31.7%). During the retrospective period, 73.0% of patients reported adverse drug reactions, while in the prospective period, 40.5% experienced adverse events, with no clinical differences between groups. The study supports the use of daratumumab regimens in frontline therapy based on real-world data. The findings provide valuable insights into the clinical outcomes of daratumumab therapy, which can help physicians make informed decisions regarding the optimal treatment approach for this patient population. Full article

Transplant oncology is an expanding area of cancer therapy that specifically emphasizes the use of liver transplantation (LT) as the preferred treatment for patients with manageable, but unresectable, tumors. The management and optimization of overall survival strategies, accompanied by an arguably decent quality of life, have been at the forefront of liver oncology treatment, as a plurality of all primary liver cancers are identified as either hepatocellular carcinoma (HCC) or cholangiocarcinoma (CCA), which are classified as highly aggressive malignancies and frequently remain asymptomatic until they progress to advanced stages, rendering curative procedures, such as resection, impractical. This has led to an increase in utilization of neoadjuvant interventions conducted prior to surgery, which has yielded favorable outcomes. Though this treatment modality has prompted further investigations into the efficacy of immune checkpoint inhibitors (ICPIs) as standalone treatments and in combination with locoregional treatments (LRTs) to bridge more patients into curative eligibility. This multidisciplinary methodology and treatment planning has seen multiple successful trials of immunotherapy regimes and combinate treatments, setting the groundwork for increasing eligibility through downstaging and “bridging” previously ineligible patients within stringent LT criteria. Surveillance after LT is a crucial component of transplant oncology. The emergence of circulating tumor DNA (ctDNA) has provided a novel approach to identifying the recurrence of cancer in its early stages. Recent research has focused on liquid biopsy, a technique that effectively identifies the dynamics of cancer. This is another innovation to demonstrate the rate at which transplant oncology is rapidly advancing, making the focus of care feel disorienting. Modalities of care are constantly evolving, but when a field is changing as rapidly as this one, it is imperative to reorient to the data and the needs of the patients. In this commentary, we reflect on the update’s utilization of ICPIs in neoadjuvant settings as well as the updates on the utilization of liquid biopsy in post-LT follow-up surveillance. Full article

Immunotherapy has revolutionized the treatment of myeloid oncologic diseases, particularly for patients resistant to chemotherapy or ineligible for allogeneic stem cell transplantation due to age or fitness constraints. As our understanding of the immunopathogenesis of myeloid malignancies expands, so too do the treatment options available to patients. Immunotherapy in myeloid malignancies, however, faces numerous challenges due to the dynamic nature of the disease, immune dysregulation, and the development of immune evasion mechanisms. This review outlines the progress made in the field of immunotherapy for myeloid malignancies, addresses its challenges, and provides insights into future directions in the field. Full article