Search Results (857)

Objective: To compare real-world PFS between BEV and OLA as maintenance therapy for PSROC, with an exploratory evaluation of clinical outcomes after OLA dose reduction. Methods: This retrospective multicenter study included 101 patients with first platinum-sensitive recurrent ovarian, fallopian tube, or primary peritoneal cancer who achieved a response to platinum-based chemotherapy and then received maintenance therapy. Patients were classified into three groups: BEV (n = 34), standard-dose OLA (n = 31), and dose-reduced OLA (n = 36). The primary endpoint was PFS; secondary endpoints were OS and adverse events. Survival outcomes were evaluated using Kaplan–Meier methods and Cox proportional hazards models. Results: In the primary comparison of all OLA-treated patients versus BEV, OLA was associated with longer PFS (HR 0.48, 95% CI 0.29–0.77), with median PFS of 19 months versus 16 months, respectively. OS did not differ significantly between groups (HR 0.60, 95% CI 0.34–1.05). In exploratory subgroup analyses, patients who underwent OLA dose reduction had numerically longer PFS than those who remained on the full dose; however, this comparison is vulnerable to time-dependent and selection biases and should be interpreted cautiously. Grade ≥ 3 hematologic toxicities were more frequent in the OLA groups but were clinically manageable. Conclusions: In real-world practice, OLA was associated with longer PFS than BEV in PSROC. Clinically necessary dose reduction appeared feasible without an obvious loss of benefit, although this finding requires cautious interpretation. Full article

Background/Objectives: TCIRG1-associated infantile osteopetrosis is a severe hereditary disorder caused by impaired osteoclast function, leading to osteosclerosis, hematological abnormalities, neurological complications, and early mortality. Early diagnosis and intervention are critical. Methods: A literature-based analysis was performed on clinical manifestations, outcomes of allogeneic hematopoietic stem cell transplantation (HSCT), immunomodulatory therapy, and experimental gene therapy and cell-based approaches, including lentiviral vectors and patient-derived induced pluripotent stem cells (iPSCs). Results: Allogeneic HSCT is the only established curative therapy, restoring osteoclast function and preventing severe complications. Early transplantation with HLA-matched donors and myeloablative conditioning provides optimal outcomes. Interferon γ1b can transiently enhance osteoclast activity but is not curative and shows variable efficacy. Preclinical studies demonstrate that lentiviral TCIRG1 delivery and transgenic correction in patient-derived iPSCs restore osteoclast function and bone resorption, with stable gene expression and minimal toxicity. Base and prime editing approaches offer potential for precise correction of single-nucleotide TCIRG1 variants, minimizing risks associated with double-strand DNA breaks. Conclusions: Allogeneic HSCT remains the standard therapy for TCIRG1-associated infantile osteopetrosis. Gene therapy and cell-based strategies represent promising adjuncts or alternatives, potentially avoiding immune-related complications and expanding therapeutic options. Further studies are needed to ensure safety, stable engraftment, and long-term efficacy, supporting translation of gene therapy into clinical practice. Full article

Introduction: Chimeric antigen receptor (CAR) T-cell therapies have revolutionized treatment for relapsed/refractory hematologic malignancies, targeting CD19 in B-cell neoplasms and BCMA in multiple myeloma, with response rates exceeding 80%. However, long-term risks, including therapy-related myeloid neoplasms, such as myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), are emerging 6–24 months post infusion, potentially linked to lymphodepleting chemotherapy, clonal hematopoiesis expansion, and inflammatory milieus. This FAERS pharmacovigilance analysis quantified MDS/AML reporting across seven FDA-approved CAR-T products to detect antigen-specific signals unattainable in pivotal trials with limited follow-up. Methods: Adverse event reports from FAERS (1 January 2013–10 February 2025) were queried for tisagenlecleucel, axicabtagene ciloleucel, brexucabtagene autoleucel, lisocabtagene maraleucel, obecabtagene autoleucel, idecabtagene vicleucel, and ciltacabtagene autoleucel, focusing on MedDRA terms for MDS/AML. Duplicates and ambiguous cases were excluded. Disproportionality was assessed using reporting odds ratios (RORs; lower 95% CI >1 signaling significance), comparing CAR-T-event pairs to database background, with subgroup analyses by antigen target. Results: Among 14,093,557 reports, CAR-T products linked to 303 MDS (brexucabtagene autoleucel ROR 97.93 [72.18–132.87], n = 44; axicabtagene ciloleucel ROR 58.70 [50.34–68.44], n = 172) and 129 AML cases (axicabtagene ciloleucel ROR 22.89 [18.23–28.73], n = 76). Signals were consistent across CD19- and BCMA-directed agents, absent only for recently approved obecabtagene autoleucel. Conclusions: CAR-T therapies exhibit disproportionate MDS/AML reporting in FAERS, supporting class-wide late hematologic toxicity in pretreated patients with clonal hematopoiesis. Enhanced surveillance, baseline profiling, and marrow evaluation for cytopenias are warranted, balancing curative benefits. Full article

Acute myeloid leukemia (AML) remains a highly morbid malignancy in which outcomes are constrained not only by disease refractoriness and relapse, but also by therapy-related toxicity—particularly infections, mucosal injury, and delayed hematopoietic reconstitution. The gut microbiota has emerged as a potentially modifiable layer of host vulnerability and resilience during AML treatment. Microbiome disruption is detectable already at diagnosis, even in antibiotic-naïve patients, and is often characterized by reduced community diversity, depletion of anaerobic taxa linked to short-chain fatty acids (SCFAs) production, and enrichment of pathobiont-associated profiles. During induction, cytotoxic therapy and antimicrobials precipitates diversity loss, domination events, and persistent shifts beyond discharge. Clinically, the most consistent translational signal is the association between baseline or early-treatment microbiome features and infectious outcomes, while emerging data suggest that diagnosis-time microbiome structure may also relate to hematologic recovery kinetics. Mechanistic models converge on pathways linking barrier integrity, microbial metabolites (notably butyrate and other SCFAs), immune calibration, and inflammatory translocation of microbial products. These insights support hypotheses: antimicrobial stewardship may preserve microbiome function; ecosystem repair strategies such as autologous fecal microbiota transfer (A-FMT) are feasible and can restore community structure; and metabolite or nutritional interventions merit evaluation in immunocompromised hosts. Regimen-specific microbiome effects and microbiome–drug interactions suggest that treatment choice could have downstream microbiome-mediated consequences. We synthesize evidence, outline interventional concepts, and define methodological priorities for next-generation trials assessing causality and clinical benefit. Progress will require longitudinal sampling, multi-omic integration (metabolomics, resistomics, and barrier/inflammatory biomarkers), and interventional designs linking microbiome dynamics to clinically meaningful outcomes. Full article

Background: Hormone receptor-positive (HR+), Human Epidermal growth factor Receptor 2 (HER2-negative) metastatic breast cancer (MBC) represents a substantial proportion of breast cancer cases in Saudi Arabia. Despite the established efficacy of cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors, particularly Palbociclib, in randomized control trials, real-world data from local institutions in Saudi Arabia remain limited. Objectives: This study aimed to evaluate progression-free survival (PFS), overall survival (OS), and toxicity profile among HR+, HER2-negative MBC female patients treated with Palbociclib at King Fahad Medical City (KFMC). Methods: A retrospective study was conducted on female patients with HR+/HER2-negative MBC treated with oral palbociclib combined with endocrine therapy (ET) at KFMC between January 2021 and September 2024. Data were collected from electronic health records. Descriptive statistics were conducted using mean for continuous variables and frequency for categorical variables. Survival analyses were conducted using Cox regression, log-rank tests and Kaplan–Meier analysis. Results: A total of 169 female patients with HR+/HER2− MBC were included. In the first-line setting, the median PFS was 20.14 months (95% CI: 14.65–30.49), compared with 11.3 months (95% CI: 7.98–not estimable) in the second-line setting. For OS, the median OS values were 53.1 months (95% CI: 41.2–not estimable) in the first-line group and 23.7 months (95% CI: 18.5–not estimable) in the second-line group. Significant predictors of shorter PFS included age, Body Mass Index (BMI), type of ET, cancer type, line of therapy, family history of cancer, and history of VTE. Visceral metastasis (HR = 3.087; p = 0.0229) and ECOG performance status of 4 (HR = 13.86; p = 0.0156) were associated with significantly shorter OS. The most common hematological adverse events (AEs) were neutropenia (45.6%), followed by anemia (5.9%), leukopenia (5.3%), and back pain (5.3%). Most toxicities were managed with dose reduction, holding treatment, or supportive care. Conclusions: Palbociclib demonstrated favorable survival outcomes and a manageable safety profile, with neutropenia being the most common AE. This study provides region-specific real-world evidence supporting the use of Palbociclib in HR+/HER2− MBC. These findings align with global trial data and highlight the importance of individualized treatment in clinical practice. Full article

Chimeric antigen receptor–natural killer (CAR-NK) cell therapy is a promising immunotherapy for hematological malignancies. While engineered interleukin15 (IL15) variants like membrane-bound IL15 (mbIL15) and the IL15/IL15Rα heterodimer (RLI) can enhance NK cell activity, their relative efficacy and safety as armor for CAR-NK cells remain unclear. This study systematically evaluated primary human CAR-NK cells co-expressing an anti-CD19 CAR (19ζ) with soluble IL15, mbIL15, or RLI. We found that 19ζ-RLI CAR-NK cells exhibited superior IL15 secretion, proliferation, cytotoxicity, and migration in vitro, and effectively controlled tumors in vivo. However, all IL15-armored constructs, particularly 19ζ-RLI, induced lethal toxicity in mice, characterized by CAR-NK hyperproliferation and elevated systemic IL15. Transcriptomic analysis revealed that this toxicity correlated with a hyperactive molecular state driven by persistent IL15 signaling. In conclusion, this study suggests that constitutive IL15 armoring can be a potent but risky strategy for enhancing CAR-NK cells, with RLI being the most potent yet toxic exemplar of this general principle. Our findings highlight the necessity of incorporating safety-optimized strategies, such as inducible cytokine expression, into the design of cytokine-armored CAR-NK therapies for clinical translation. Full article

The treatment paradigm for HER2-positive metastatic breast cancer has evolved from continuous chemotherapy-based regimens to a model of finite chemotherapy induction followed by sustained antibody-driven disease control. The CLEOPATRA trial established dual HER2 blockade with trastuzumab and pertuzumab plus a taxane as the biological and clinical anchor of this approach, demonstrating that chemotherapy is administered for a defined induction period, after which antibody maintains disease suppression. An increasing body of clinical evidence indicates that antibody-based regimens can be combined with targeted agents, including CDK4/6 inhibitors or HER2 tyrosine kinase inhibitors, to achieve durable disease control without the need for continuous chemotherapy. In the PATINA trial, the addition of palbociclib to trastuzumab, pertuzumab, and endocrine therapy was associated with a clinically meaningful improvement in progression-free survival in hormone receptor-positive, HER2-positive metastatic breast cancer. At the same time, quality of life was maintained despite higher rates of hematologic toxicity. More recently, HER2-CLIMB-05 demonstrated that the addition of tucatinib to dual HER2 antibody therapy significantly prolonged progression-free survival, supporting a model of sustained, multi-agent HER2 pathway suppression. The monarcHER trial provided biological proof of concept that antibody plus CDK4/6 inhibition can achieve disease control without chemotherapy in hormone receptor-positive, HER2-positive disease. Collectively, these advances support a translational framework in which antibody therapy serves as a central component of treatment strategies, with targeted partners selected according to tumor biology and prior therapy. This review summarizes the biological basis, clinical evidence, and future perspectives of antibody-driven maintenance in HER2-positive metastatic breast cancer. Full article

Clonal hematopoiesis of indeterminate potential (CHIP) is the clonal expansion of somatically mutated hematopoietic stem cells (HSCs) in the bone marrow. CHIP mutations are relatively common in multiple myeloma (MM) and have been identified as potential biomarkers for poorer survival outcomes. MM is a hematological malignancy that, despite treatment advances, remains aggressive and incurable for many patients. The potential impact of CHIP mutations on the outcomes of MM treatments has been the topic of several recent studies, yet both the magnitude and the modality by which CHIP exerts its negative effects on treatment and disease progression remain to be fully elucidated. Evidence suggests that CHIP mutations may contribute to inferior survival and treatment tolerances, as well as contribute to greater treatment toxicity and related frailty. In this review, we synthesize and discuss the available literature to provide an updated understanding of the complex role that CHIP plays in altering the MM microenvironment, and the resulting impact on standard MM treatments, autologous stem cell transplant (ASCT) and B-cell maturation antigen (BCMA)-targeted therapy/CAR-T, and the important role of immunomodulatory drug (IMiD) maintenance therapy in clinical outcomes. Full article

Background/Objectives: Cancer is the second leading cause of death globally, and resistance to immunotherapy requires new strategies. One promising approach is cross-line immunotherapy, defined as retreatment with the same or different immune checkpoint inhibitors after progression on prior immunotherapy. Understanding the efficacy and safety of this innovative treatment modality is critical for advancing cancer care. Methods: In this study, we evaluated outcomes of cross-line immunotherapy in a cohort of 105 patients with various malignant tumors at Beijing Friendship Hospital. The primary endpoints of the study included progression-free survival (PFS2) and overall survival (OS), measured from the initiation of cross-line immunotherapy. All patients received treatment regimens determined by their physicians. The study aimed to evaluate the efficacy of cross-line immunotherapy, with or without other therapies. Results: The study reported a median PFS2 of 6.9 months (95% CI: 4.7–8.1) and a median OS of 12.9 months (95% CI: 11.7–NA). The objective response rate (ORR) was 11%, while the disease control rate (DCR) was 77%. Although 35.2% of patients experienced grade 3 or higher immune-related adverse events, primarily hematological toxicities, no specific immune treatment-related hematological events were noted. Additionally, elevated D-dimer levels and hyponatremia emerged as prognostic factors associated with poorer outcomes, whereas hypertriglyceridemia correlated with enhanced survival. A nomogram developed for predicting PFS2 and OS demonstrated high discriminative capacity. Conclusions: These findings show that cross-line immunotherapy is safe and effective for patients with malignant tumors. It offers a viable option for patients who are progressing after initial treatments, which highlights the need for personalized strategies. Full article

Background: Although multiple pomalidomide-based combinations are active in relapsed and/or refractory multiple myeloma (RRMM), comparative data to guide regimen selection remain limited. Methods: A total of 230 patients with RRMM from 12 centers in China who received pomalidomide-based regimens were included in this retrospective analysis. Overall response rate (ORR) and progression-free survival (PFS) were compared across regimens incorporating bortezomib or ixazomib (V/IPD), carfilzomib (KPD), or daratumumab (DPD), and multivariable analyses were performed to identify prognostic factors. Results: The overall ORR was 73.9%, with rates of 63%, 79%, and 85% in the V/IPD (n = 66), KPD (n = 69), and DPD (n = 95) cohorts, respectively. ORR differed significantly between V/IPD and DPD (p = 0.0165), driven by a higher proportion of ≥VGPR in the DPD group. The median PFS for the entire cohort was 17.4 months (95% CI: 13.7–20.1), compared with 15.4 months (95% CI: 12.8–20.5), 14.2 months (95% CI: 6.9–not estimable), and 19.2 months (95% CI: 15.1–24.9) for V/IPD, KPD, and DPD, respectively, without significant differences. In multivariable analysis, DPD was associated with improved ORR (HR 4.83, p < 0.001) but not with PFS. R-ISS stage III predicted inferior response (HR 0.35, p = 0.04), whereas ≥3 prior lines of therapy correlated with shorter PFS (HR 1.77, p = 0.012). Adverse events were predominantly hematologic, with limited grade 3–4 toxicity and no treatment-related mortality. Conclusions: This multicenter real-world analysis clarifies the relative positioning of commonly used pomalidomide-based regimens in RRMM and underscores the importance of treatment timing and disease stage in optimizing outcomes. Full article

Background: Cancer during pregnancy is a rare but increasingly encountered condition due to delayed childbearing and improved survival of women with cancer. The coexistence of malignancy and pregnancy poses complex diagnostic and therapeutic challenges, requiring careful balance between maternal prognosis and fetal safety. Objective: This review aims to summarize current evidence on the diagnosis and multidisciplinary management of cancer during pregnancy, focusing on the safe use of oncologic therapies, obstetric decision-making, and maternal and fetal outcomes. Methods: A narrative review was conducted based on literature identified in PubMed/MEDLINE, Scopus, and Web of Science from January 2000 to September 2025. Search terms included pregnancy-associated cancer, oncologic treatment during pregnancy, obstetric management, and fetal outcomes. Relevant clinical guidelines, registry data, and reference lists were also reviewed. Results: Breast cancer, cervical cancer, melanoma, hematologic malignancies, and gestational trophoblastic neoplasia represent the most frequently reported cancers during pregnancy. Evidence indicates that selected cancer treatments can be administered safely without compromising maternal prognosis. Chemotherapy after the first trimester is generally associated with acceptable fetal outcomes. Physiological changes in pregnancy may delay diagnosis and influence drug pharmacokinetics. Radiotherapy, targeted therapies, and immunotherapies remain limited because of potential fetal toxicity. Avoiding iatrogenic prematurity is a central principle of obstetric management. Conclusions: Cancer during pregnancy should no longer be considered an absolute therapeutic dilemma. With individualized multidisciplinary care, effective maternal treatment and favorable fetal outcomes are increasingly achievable. Full article

Purpose: Bortezomib (BTZ) is widely used in multiple myeloma (MM), but its toxicity shows marked interindividual variability. This study aimed to identify pharmacogenetic and clinical factors associated with BTZ-related adverse drug reactions (ADRs). Methods: A retrospective and prospective observational study was conducted in 127 MM patients treated with BTZ-based regimens. Polymorphisms in CYP enzymes and ABCB1 were genotyped using qPCR. Associations between genetic variants, treatment response, and ADRs were assessed using univariate and multivariate analyses with Benjamini–Hochberg correction. Results: ADRs occurred in 98.4% of patients, most commonly gastrointestinal toxicity (49%), general toxicity (46%), and peripheral neuropathy (39%). Women showed higher rates of gastrointestinal toxicity and non-peripheral neurotoxicity. Multivariate analysis identified the ABCB1 C1236T A/G genotype as protective against gastrointestinal toxicity, while the CYP3A4 intermediate metabolizer phenotype was associated with increased psychiatric toxicity. TP53 mutations were independently associated with hematologic and renal toxicity. Kaplan–Meier analysis showed earlier onset of peripheral neuropathy and respiratory toxicity in CYP3A4 intermediate and poor metabolizers. Conclusions: Genetic variation in ABCB1 and CYP3A4, together with clinical factors such as TP53 mutation and sex, may contribute to interindividual variability in BTZ safety in MM. These findings should be considered exploratory given the sample size and require confirmation in larger cohorts. Nonetheless, they suggest a potential role for pharmacogenomics in supporting future approaches to treatment personalization. Full article

Antibody–drug conjugates (ADCs) are reshaping the therapeutic approach to advanced gastrointestinal cancers by integrating tumor-specific monoclonal antibodies with potent cytotoxic payloads to improve targeted tumor cell destruction while minimizing systemic exposure. Compared to traditional chemotherapy, trastuzumab deruxtecan has significantly improved objective response rates and overall survival in HER2-positive gastric and gastroesophageal junction tumors after trastuzumab-based therapy. This supports its role as an important second-line or later treatment option. The ongoing advancement of ADCs targeting CLDN18.2, TROP2, and CEACAM5 indicates that this therapeutic category will continue to expand across gastrointestinal neoplasms. Nonetheless, these advancements are accompanied by a specific and clinically significant toxicity profile. Hematologic suppression, gastrointestinal side effects, hepatotoxicity, and notably interstitial lung disease (ILD) are essential consequences that may need inpatient assessment and care. Interstitial lung disease (ILD), although uncommon, may be severe or lethal if not identified immediately and treated swiftly with medication cessation and corticosteroids. In hospitalized patients, distinguishing ADC-related toxicity from infection or disease progression is often difficult owing to overlapping clinical manifestations, requiring meticulous evaluation and interdisciplinary cooperation. As ADCs are integrated into earlier treatment lines and across a broader patient population, hospital systems must evolve to ensure prompt identification, consistent management protocols, and efficient collaboration between oncology and inpatient teams. This study analyzes the mechanisms, clinical effectiveness, and safety profile of ADCs in gastrointestinal oncology, pointing out the importance of institutional preparedness to safely incorporate these medicines into standard clinical practice. These features also align ADC therapy with personalized medicine by emphasizing biomarker-guided patient selection and individualized toxicity monitoring. Full article

Background: An increasing number of reports showed patients with bulky tumors after lattice radiation therapy (LRT) treatment achieved good local control. However, in these reports, LRT was previously used primarily for palliation. We reported a case that LRT plays a synergistic role in the radical treatment of locally advanced bulky cervical cancer (LABCC) combined with INTERLACE study protocol. Methods: The patient was a 54-year-old female with LABCC and treated with LRT combined with the INTERLACE study protocol. She received three fractions of 3 Gy each to the gross tumor volume (GTV) and three fractions of 9 Gy each to the lattice therapy volume (LTV), on an emergent basis, using volumetric modulated arc therapy (VMAT). Subsequently, according to the INTERLACE study protocol, chemotherapy and radiotherapy were carried out and the standard follow-up examinations were conducted. Adverse events (AEs) were assessed according to the Common Terminology Criteria for AEs (CTCAE) version 5.0. Results: The patient initially received LRT, which reduced the tumor burden and controlled bleeding. After this was combined with the INTERLACE study protocol, the complete clinical response (cCR) was achieved and they maintained this status for 13 months after the completion of concurrent chemoradiotherapy (CCRT), with only manageable grade IV hematological toxicity observed after the completion of CCRT. During this period, only manageable grade IV hematological toxicity (platelet count 16 × 10⁹/L, white blood cell count 0.33 × 10⁹/L) was observed. Conclusions: In this case, LRT combined with INTERLACE study protocol appears to be a safe and effective for the treatment of LABCC which improved the patient’s quality of life without uncontrolled treatment-related toxicity. Full article

Chimeric antigen receptor T (CAR-T) cell therapy has become a standard of care for many hematological malignancies, and has significantly transformed treatment outcomes. However, CAR-T therapy is associated with specific toxicities, including infections. Although the anti-CD19 CAR-T risks are well-characterized, infectious complications following B-cell maturation antigen (BCMA)-directed CAR-T in multiple myeloma (MM) remain under-researched. In this study, we evaluated the incidence and clinical impact of cytomegalovirus (CMV), Epstein–Barr virus (EBV), and adenovirus (ADV) reactivations in 75 patients receiving anti-BCMA CAR-T for MM, and compared them to 60 patients receiving commercial anti-CD19 CAR-T for B-cell lymphoma (BCL). The viral reactivation rates were 20% for CMV and 8% for EBV in the MM group, vs. 31.7% and 3%, respectively, in the BCL group. No ADV reactivations were seen in either cohort. Most of the CMV reactivations (87% in the MM cohort and 68.5% in the BCL cohort) were asymptomatic and clinically insignificant, and had no impact on progression-free survival (PFS) or overall mortality. Overall, these findings suggest that although CMV and EBV reactivations are relatively common after anti-BCMA CAR-T, they are rarely associated with meaningful disease, and the risks do not exceed those of CD19-directed therapy. Thus, routine pre-emptive screening for these viruses may be unwarranted in asymptomatic patients. Full article