Search Results (165)

Relapsed/refractory diffuse large B-cell lymphoma and other non-Hodgkin lymphomas represent significant clinical challenges, particularly in patients who have exhausted standard immunochemotherapy and cellular therapies. Bispecific antibodies and antibody–drug conjugates have emerged as promising treatments, offering targeted and more effective treatment options compared to current standards. Bispecific antibodies, including epcoritamab and glofitamab, third-line therapies for diffuse large B-cell lymphoma, are recombinant immunoglobulins engineered to recognize two distinct antigens or epitopes simultaneously. This capability enhances therapeutic precision by bridging immune effector cells and tumor cells and modulating multiple signaling pathways involved in the pathogenesis of non-Hodgkin lymphoma. In the context of new therapies, antibody–drug conjugates, such as loncastuximab tesirine, are therapies composed of monoclonal antibodies linked to cytotoxic agents, in which the antibody selectively binds to tumor-associated antigens, delivering the cytotoxic payload directly to cancer cells while minimizing off-target effects. They combine the specificity of antibodies with the potency of chemotherapy, offering enhanced efficacy and safety in hematological malignancies. Ongoing clinical trials are investigating other molecules like odronextamab and the use of bispecific antibodies in combination regimens and earlier lines of therapy. The aim of this review is to explore actual therapies in relapsed/refractory diffuse large B-cell lymphoma, focusing on bispecific antibodies and antibody–drug conjugates. Full article

Background/Objectives: The tumor microenvironment (TME) plays a critical role in cancer progression by shaping immune responses and influencing patient outcomes. We hypothesized that the relative proximity of specific immune cell pairs to cancer cells within the TME could help predict their pro- or anti-tumor functions and reflect clinically relevant immune dynamics. Methods: We analyzed imaging mass cytometry (IMC) data from lung adenocarcinoma (LUAD) and triple-negative breast cancer (TNBC) cohorts. For each immune cell pair, we calculated a relative distance (RD) score, which quantifies the spatial difference in proximity to cancer cells. We assessed the prognostic and predictive significance of these RD-scores by comparing them with conventional features such as cell fractions, densities, and individual cell distances. To account for variations in cell abundance, we also derived normalized RD-scores (NRD-scores). Results: RD-scores were more strongly associated with overall patient survival than standard immunological metrics. Among all immune cell pairs, the RD-score comparing the proximity of B cells to that of intermediate monocytes showed the most significant association with improved survival. In TNBC, RD-scores also improved the distinction between responders and non-responders to immunochemotherapy and chemotherapy. Normalized RD-scores reinforced these findings by minimizing the influence of cell density and further highlighting the importance of immune cell spatial relationships. Conclusions: RD-scores offer a spatially informed biomarker that outperforms traditional metrics in predicting survival and treatment response. This approach provides a new perspective on immune cell behavior in the TME and has potential utility in guiding personalized cancer therapies and patient stratification. Full article

This retrospective cohort study evaluated characteristics, treatment patterns, and clinical outcomes in adults with locally advanced/metastatic urothelial carcinoma (la/mUC) receiving first-line (1L) systemic treatment with or without avelumab 1L maintenance (1LM) between January 2020 and July 2023. The index date was the first date with a claim for 1L systemic therapy after a la/mUC diagnosis. Patients with continuous health plan enrollment for ≥6 months before and ≥1 month after the index date were identified from Carelon Research’s Healthcare Integrated Research Database. Of 2820 patients receiving 1L treatment, 37.0% received platinum-based chemotherapy (PBC); 39.0%, immuno-oncology (IO) monotherapy; and 24.0%, other therapies. Renal disease and other comorbidities influenced 1L regimen choice. Healthcare resource utilization (HCRU) and costs were reported for patients receiving second-line (2L) treatment. HCRU was high in 32.8% of patients (926 of 2820) who received 2L treatment. Median all-cause direct medical costs per patient per month were USD 15,859, USD 19,781, USD 11,346, and USD 9516 for 1L PBC, 1L PBC + avelumab 1LM, 1L IO monotherapy, and 1L other therapies, respectively. Most direct healthcare costs were attributed to all-cause outpatient visits. Full article

Background/Objectives: Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare and aggressive cutaneous lymphoma, often misdiagnosed due to nonspecific clinical features. Early diagnosis and treatment remain challenging. Methods: We report the case of a 31-year-old female with a chronic non-healing gluteal wound initially treated as an abscess. The lack of improvement prompted repeated investigations, culminating in the diagnosis of SPTCL with an alpha–beta T-cell phenotype. Results: Management involved combined chemotherapy and surgical wound reconstruction. Six cycles of CHOEP-21 chemotherapy led to complete clinical remission. A soft tissue defect superinfected with multidrug-resistant organisms was successfully reconstructed using Integra Dermal Regeneration Template followed by split-thickness skin grafting. Conclusions: This case highlights the diagnostic complexity of SPTCL and the therapeutic potential of dermal matrix application in complex wound management, especially in immuno-compromised patients. Full article

Machine learning (ML) algorithms hold the potential to outperform the selection of patients for immunotherapy (ICIs) compared to previous biomarker studies. We analyzed the predictive performance of ML models and compared them to traditional clinical biomarkers (TCBs) in the field of gastrointestinal (GI) cancers. The study has been registered in PROSPERO (number: CRD42023465917). A systematic search of PubMed was conducted to identify studies applying different ML algorithms to GI cancer patients treated with ICIs using tumor RNA gene expression profiles. The outcomes included were response to immunotherapy (ITR) or survival. Additionally, we compared the ML methodology details and predictive power inherent in the published gene sets using 5-fold cross-validation and logistic regression (LR), on an available well-defined ICI-treated metastatic gastric cancer (GC) cohort (n = 45). A set of standard clinical ICI biomarkers (MLH, MSH, and CD8 genes, plus PMS2 and PD-L1)) and de-novo calculated principal components (PCs) of the original datasets were also included as additional points of comparison. Nine articles were identified as eligible to meet the inclusion criteria. Three were pan-cancer studies, five assessed GC, and one studied colorectal cancer (CRC). Classification and regression models were used to predict ICI efficacy. Next, using LR, we validated the predictive power of applied ML algorithms on RNA signatures, using their reported receiver operating characteristics (ROC) analysis area under the curve (AUC) values on a well-defined ICI-treated gastric cancer (GC) dataset (n = 45). In two cases our method has outperformed the published results (reported/LR comparison: 0.74/0.831, 0.67/0.735). Besides the published studies, we have included two benchmarks: a set of TCBs and using principal components based on the whole dataset (PCA, 99% explained variance, 40 components). Interestingly, a study using a selected gene set (immuno-oncology panel) with AUC = 0.83 was the only one that outperformed the TCB (AUC = 0.8) and the PCA (AUC =0.81) results. Cross-validation of the predictive performance of these genes on the same GC dataset and an investigation of their prognostic role on a collated multi-cohort GC dataset of n = 375 resected, or chemotherapy-treated patients revealed that genes mannose-6-phosphate receptor (M6PR), Indoleamine 2,3-Dioxygenase 1 (IDO1), Neuropilin-1 (NRP1), and MAGEA3 performed similarly, or better than established biomarkers like PD-L1 and MSI. We found an immuno-oncology panel with an AUC = 0.83 that outperformed the clinical benchmark or the PC results. We recommend further investigation and experimental validation in the case of M6PR, IDO1, NRP1, and MAGEA3 expressions based on their strong predictive power in GC ITR. Well-designed studies with larger sample sizes and nonlinear ML models might help improve biomarker selections. Full article

Quantitative ¹⁸F-FDG PET/CT-derived metabolic metrics are strongly associated with patient outcomes in diffuse large B-cell lymphoma (DLBCL), but the lack of consensus on optimal segmentation thresholds limits standardization. This study evaluated the prognostic value of various metabolic tumor volume (MTV) segmentation approaches in 140 stage II–IV DLBCL patients treated with standard immunochemotherapy. MTV was derived using fixed SUV (≥2.5, ≥4.0), relative (>41% SUVmax), and adaptive (liver-to-background) thresholds. Baseline MTV metrics significantly correlated with 3-year overall survival (OS3) in univariate analysis in overall cohort, with MTV41 showing the strongest association (HR: 1.27; p = 0.003). MTV25 and MTV41 remained significant in the stage 4 patient subgroup. However, in multivariate analysis, no MTV metric independently predicted OS3 when adjusted for the International Prognostic Index (IPI), which remained the dominant predictor (HR: 1.95; p < 0.0001). ROC analysis confirmed superior AUC for IPI (0.76) over PET-based metrics (0.64–0.69). Predictive models integrating IPI with PET metrics were robust but failed to improve prognostic accuracy beyond IPI alone. Although PET-derived MTV metrics provide prognostic value in univariate analysis, threshold selection has minimal impact, and their added value is limited when combined with IPI, reinforcing its role as the most reliable survival predictor in DLBCL. Full article

Background: Pseudomonas aeruginosa (PSA) infections are associated with a high recurrence rate and high mortality in immuno-compromised patients. There are limited studies regarding pediatric hematopoietic cell transplantation recipients. Aim: The nationwide multicenter study was conducted to analyze the epidemiology of PSA infections in children treated with chemotherapy (PHO, pediatric hematology and oncology) or undergoing hematopoietic allogeneic or autologous cell transplantation (HCT) in the period 2014–2023. Methods: We retrospectively analyzed the clinical and microbiological data of children who underwent anticancer therapy or hematopoietic cell transplantation in 17 Polish PHO centers and six pediatric HCT centers. The data were collected in two-year intervals. Results: During the 10-year study period, a total of 1629 HCTs (both autologous and allogeneic) and 9614 children newly diagnosed with neoplasms were analyzed. The cumulative incidence of PSA infection was similar in both groups (6.71% in PHO vs. 6.32% in HCT, p = 0.624). The total number of PSA bloodstream infections was comparable in the PHO and HCT groups (31.9% vs. 26.2%; p = 0.223). In both analyzed groups, the antipseudomonal drugs of choice were as follows: meropenem, ceftazidime, and tazobactam/piperaciline in combination with other antibiotics. In the HCT group, high rates of meropenem (20.4%) and tazobactam/piperaciline (18.4%) non-susceptibility were observed. This led to colistin therapy in 5.3% of patients. There was no difference in the median antibiotic therapy time in both groups; however, the survival rates from PSA infection were significantly lower in the HCT group (89.3% vs. 96.0%, p = 0.004). Conclusions: Although the risk of infection and the occurrence of resistant bacterial strains in HCT patients were comparable with those in PHO patients, the outcome of PSA infections was better in the PHO setting. Full article

Monoclonal antibodies (mAbs) have become a cornerstone in the treatment of follicular lymphoma (FL), offering highly specific therapeutic targeting that enhances efficacy while minimizing systemic toxicity. Their mechanisms of action include antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), and direct apoptotic signaling, effectively mediating malignant B-cell depletion. Anti-CD20 mAbs, such as rituximab and obinutuzumab, have significantly improved progression-free survival (PFS) and overall survival (OS), establishing immunochemotherapy as the standard of care for FL. However, the emergence of treatment resistance, often characterized by CD20 antigen downregulation or immune escape, has prompted the development of next-generation mAbs with enhanced effector functions. Bispecific antibodies (BsAbs), which simultaneously engage CD20-expressing tumor cells and CD3-positive cytotoxic T cells, have emerged as a novel immunotherapeutic strategy, redirecting T-cell activity to eliminate malignant B cells independently of major histocompatibility complex (MHC) antigen presentation. Additionally, antibody–drug conjugates (ADCs) offer a targeted cytotoxic approach by delivering potent chemotherapeutic payloads directly to tumor cells while limiting off-target effects. The integration of mAbs with immune checkpoint inhibitors and immunomodulatory agents is further enhancing treatment outcomes by overcoming immunosuppressive mechanisms within the tumor microenvironment. Despite these advancements, challenges remain, including optimizing the treatment sequence, mitigating immune-related toxicities—particularly cytokine release syndrome (CRS)—and identifying predictive biomarkers to guide patient selection. As the role of monoclonal antibodies continues to expand, their integration into therapeutic regimens is transforming the management of FL, paving the way for chemotherapy-free treatment approaches and long-term disease control. This review provides an updated overview of mAbs therapies for FL, emphasizing the advances brought by BsAbs and ADCs toward more tailored and effective treatments. Full article

Background: In recent years, there has been an exponential growth in global anti-cancer drug research, prompting the necessity for comprehensive analyses of publication output and thematic shifts. Methods: This study utilized a comprehensive set of PubMed records from 1962 to 2024 and examined growth patterns, content classification, and co-occurrence of key pharmacological and molecular terms. Results: Our results highlight an exponential rise in publications, with an annual compound growth rate of over 14%, influenced by advancements in digital knowledge sharing and novel therapeutic breakthroughs. A pronounced surge occurred during the COVID-19 pandemic, suggesting a sustained shift in research dynamics. The content analyses revealed a strong emphasis on classical chemotherapeutic agents—often studied in combination with targeted therapies or immunotherapies—and a growing focus on immune checkpoint inhibitors and vaccine platforms. Furthermore, co-occurrence networks indicated robust links between chemotherapy and supportive care, as well as emerging synergies between immuno-oncology, precision medicine approaches. Conclusions: Our study suggests that while novel modalities are reshaping treatment paradigms, chemotherapy remains central, underscoring the value of integrative regimens. This trend toward personalized, combination-based strategies indicates a transformative era in oncology research, where multidimensional data assessment is instrumental in guiding future therapeutic innovations. Full article

Metastatic prostate cancer (mPCa) remains a significant cause of cancer-related mortality in men. Advances in molecular profiling have demonstrated that the androgen receptor (AR) axis, DNA damage repair pathways, and the PI3K/AKT/mTOR pathway are critical drivers of disease progression and therapeutic resistance. Despite the established benefits of hormone therapy, chemotherapy, and bone-targeting agents, mPCa commonly becomes treatment-resistant. Recent breakthroughs have highlighted the importance of identifying actionable genetic alterations, such as BRCA2 or ATM defects, that render tumors sensitive to poly-ADP ribose polymerase (PARP) inhibitors. Parallel efforts have refined imaging—particularly prostate-specific membrane antigen (PSMA) positron emission tomography-computed tomography—to detect and localize metastatic lesions with high sensitivity, thereby guiding patient selection for PSMA-targeted radioligand therapies. Multi-omics innovations, including liquid biopsy technologies, enable the real-time tracking of emergent AR splice variants or reversion mutations, supporting adaptive therapy paradigms. Nonetheless, the complexity of mPCa necessitates combination strategies, such as pairing AR inhibition with PI3K/AKT blockade or PARP inhibitors, to inhibit tumor plasticity. Immuno-oncological approaches remain challenging for unselected patients; however, subsets with mismatch repair deficiency or neuroendocrine phenotypes may benefit from immune checkpoint blockade or targeted epigenetic interventions. We present these pivotal advances, and discuss how biomarker-guided integrative treatments can improve mPCa management. Full article

In the recent 2024 ESMO guidelines, the combination of venetoclax and ibrutinib was listed as one of the first-line treatment options for CLL patients. These drugs were first-in-class medicines that revolutionized CLL management, extending patients’ overall survival even in cases refractory to immunochemotherapy. However, since the approval of both compounds, more and more Bruton Tyrosine Kinase inhibitors (BTKis) and B-cell lymphoma 2 inhibitors (BCL2is) have been discovered. Their efficacy and safety are the reasons for their use in monotherapy among both treatment-naïve and relapsed patients with CLL. Currently, several ongoing clinical trials are investigating the rationale for the combination of BCL2is and BTKis. In this review, we discuss the recent advancements in the field of co-therapy with BTKis and BCL2is. Full article

Avelumab first-line maintenance (1LM) is approved for patients with locally advanced or metastatic urothelial carcinoma (la/mUC) who do not have disease progression after platinum-based chemotherapy (PBC). This retrospective study describes real-world treatment patterns and clinical outcomes in patients with la/mUC who initiated first-line (1L) systemic treatments, including avelumab 1LM, within iKnowMed, the US community oncology electronic health records database, between 1 December 2019 and 30 November 2023 and followed through 28 February 2024. In total, 1658 patients with la/mUC initiated 1L treatment: immuno-oncology (IO) monotherapy (41.2%), PBC only (32.4%), PBC followed by avelumab 1LM (11.2%), and other treatments (15.1%). The median OS (95% CI) from the start of 1L treatment was 20.4 (13.8, 30.0), 11.0 (8.5, 14.5), and 14.6 (12.6, 17.3) months for cisplatin-based only, carboplatin-based only, and IO monotherapy, respectively. Among the overall population, 36.1% and 11.8% of patients received second-line (2L) and third-line treatment, respectively. The median (95% CI) OS from the start of avelumab 1LM was 18.5 (13.8, 23.8) months. After discontinuation of avelumab 1LM, 43.5% received 2L treatment, and 59.3% of those received enfortumab vedotin (EV); the median (95% CI) OS from start of 2L EV was 12.7 (7.2, 16.5) months. Survival outcomes among patients treated with avelumab 1LM and 2L EV are consistent with respective clinical trials and other real-world studies. Full article

Follicular lymphoma (FL) is an indolent, rarely curable B-cell malignancy with a heterogeneous clinical course. While generally treatable, FL is characterized by remissions and relapses, and its clinical presentation varies widely. Rituximab has revolutionized FL treatment, significantly improving overall survival over the past two decades. Risk assessment typically relies on histological grade, tumor burden, and the Follicular Lymphoma International Prognostic Index, which incorporates factors like age, hemoglobin level, and Ann Arbor stage. However, these indices have limitations in fully capturing the clinical variability of FL. Some patients experience indolent disease for extended periods without requiring treatment, while others present with aggressive forms resistant to standard therapies. This review examines various prognostic factors in FL, including the FLIPI, FLIPI2, PRIMA-PI, and m7-FLIPI. The FLIPI, based on five risk factors, stratifies patients into low-, intermediate-, and high-risk groups. The FLIPI2 incorporates beta2-microglobulin and the longest diameter of the largest involved node, offering improved prognostication. The PRIMA-PI, designed for patients receiving rituximab-containing regimens, uses beta2-microglobulin, bone marrow involvement, and the longest diameter of the largest involved node. The m7-FLIPI integrates mutational status with FLIPI2 parameters, further refining risk stratification. The review also discusses clinical parameters like maximum standardized uptake value on PET/CT and lymphocyte/monocyte ratio as prognostic factors. A high SUVmax and low lymphocyte/monocyte ratio identify high-risk patients. While FL remains incurable, advances in immunochemotherapy and targeted therapies have improved outcomes. This review provides a comprehensive overview of prognostic tools in FL, emphasizing the importance of risk stratification for personalized treatment strategies. Full article

Primary mediastinal large B-cell lymphoma (PMLBCL) is a rare, aggressive B-cell lymphoma, sharing common features with diffuse large B-cell lymphoma (DLBCL) and Hodgkin lymphoma (HL). PMLBCL is usually cured with single-hit immunochemotherapy in the first-line setting. Relapses tend to be aggressive and may be unresponsive to conventional chemotherapy. Autologous stem cell transplant (ASCT) remains a viable option for chemosensitive patients; nevertheless, targeted therapies appear to be highly promising. Checkpoint inhibitors (CPIs) have already transformed the course of relapse/refractory disease, while CD-19-directed Chimeric Antigen Receptor (CAR) T-cell therapy may produce remarkably favorable outcomes. The exact position of CAR T-cells and CPIs in the treatment algorithm, along with the role of radiotherapy and ASCT, remains to be precisely determined. In the current review, we aim to present the recent research on targeted agents in PMLBCL and define their sequencing within the treatment algorithm, mainly in the relapse/refractory setting. Full article

Understanding the relationship between the Objective Response Rate (ORR) and survival outcomes, notably Progression-Free Survival (PFS) and Overall Survival (OS), is relevant for assessing the efficacy of regimens in oncology. We evaluate the relationship between ORR, PFS and OS in immuno-oncology (IO) trials. Data from 68 clinical trials submitted to the FDA were evaluated, examining immunotherapy regimens, notably immune checkpoint inhibitors such as anti-programmed death (ligand)-1 [anti-PD-(L)1], cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) inhibitors and combination therapies [e.g., IO + IO, anti-PD-L1 + chemotherapy, anti-PD-L1 + CTLA-4, anti-PD-L1 + TKI (tyrosine kinase inhibitors)]. Studies were included based on their reporting of ORR, PFS, and OS. Of the 68 clinical trials reviewed, 55 were included in the analysis. The correlation between ORR and PFS was moderate across most immunotherapy regimens, indicating that ORR can serve as a useful predictor of short-term disease control. However, the correlation between ORR and OS was weaker, especially in trials including combination therapies, indicating that ORR alone may not reliably predict long-term survival outcomes. ORR predicts PFS better in first-line treatment but declines in later lines and remains a weak OS predictor overall. Differing degrees of correlation between ORR and survival metrics, particularly across treatment lines and combinations, are observed. While ORR can serve as a surrogate marker for PFS in IO trials, its utility in predicting OS is restricted and the interpretation of the relationship between ORR and PFS or OS is a key limitation. Rather, a decline in PFS with increasing ORR may reflect trial differences rather than a direct relationship. Future analyses should adopt better methodologies to capture these dynamics and focus on improving surrogate endpoints for immunotherapy to improve clinical trial design and patient outcomes. Full article