Introduction AlloNK is a highly scaled, non-genetically modified, allogeneic, off-the-shelf, cryopreserved NK cell therapy in development for the treatment of cancer and autoimmune diseases. AlloNK has been optimized for combination with monoclonal antibodies to enhance antibody-dependent cellular cytotoxicity and anti-tumor responses through selection of cord blood units for the CD16 high-affinity variant (158V/V) and KIR-B haplotype. Methods The objectives of this clinical trial (NCT04673617) were to assess safety and anti-tumor activity of AlloNK alone (monotherapy) and with rituximab in patients with CD20+ relapsed or refractory (R/R) non-Hodgkin Lymphoma (NHL). Patients received standard lymphodepletion (LD) and up to 4 cycles (4 weekly doses/cycle) of AlloNK at 1 × 109 or 4 × 109 cells/dose in an outpatient setting. Efficacy was evaluated using Lugano 2014 response criteria. Results As of September 4, 2025, 45 patients received AlloNK (16 across 3 monotherapy cohorts and 29 with rituximab across 4 combination cohorts). Most patients were White (82%), male (62%), with median age of 68 years, had aggressive NHL subtypes (84%), and had received a median of 4 prior lines of systemic therapy. The most common treatment-emergent adverse events (TEAEs) were hematologic in nature, as expected with the LD regimen. Infusion related-reactions (IRRs) and febrile neutropenia (7% each) were the only treatment related SAEs reported in more than 1 patient. CRS events were reported in 4 patients (9%; 3 Grade 1 cases, 1 Grade 2 case) and were attributed to IRRs (as they occurred within 24 hours of cell infusion, resolved without specialized treatment, and no cytokine elevations were noted). T cell therapy-associated toxicities such as ICANS and GvHD were not observed. There were no deaths related to AlloNK, and no patients discontinued the study from TEAEs related to AlloNK. Peripheral B-cell depletion was observed by day 15 and remained depleted over the first treatment cycle in all combination patients with detectable B cells at baseline. AlloNK was detectable in blood up to a week post-first dose but did not persist long-term. No new AlloNK-specific, anti-HLA antibodies were observed. The objective response rate was 37.5% and 55.2% in the monotherapy and combination treatment groups, respectively. In the 14 patients who were naïve to prior CAR-T therapies, 64.3% had complete responses and the Kaplan-Meier estimate of median duration of response was not reached but was at least 22.7 months. Conclusions The combination of AlloNK and rituximab was well-tolerated with promising efficacy seen in a heavily pretreated R/R NHL patient population, including older patients. No toxicities associated with T cell therapies (e.g., high rates of CRS and ICANS) were observed. These findings support the safe administration of AlloNK with rituximab in outpatient settings for oncology and autoimmune indications.
Cryptococcus neoformans is a yeast-like fungus found in soil contaminated with avian droppings. It most often produces disseminated disease in immunocompromised hosts, particularly individuals with impaired T-cell mediated immunity such as those with HIV infection, patients receiving corticosteroids or other immunosuppressive therapy, and solid organ transplant recipients. The usual clinical manifestations are meningoencephalitis and pulmonary involvement, and it remains the most common systemic mycosis in patients with acquired immunodeficiency syndrome. Although the organism can involve nearly any organ, gastrointestinal cryptococcosis is exceedingly rare and has been described only in isolated case reports. Gastric and intestinal disease may present with acute abdominal symptoms or with more indolent features such as dyspepsia, nausea, vomiting, diarrhea, or melena. Diagnosis depends on endoscopic evaluation with histopathological confirmation, yet the condition is frequently unrecognized during life and is often identified primarily at postmortem examination. Reported endoscopic findings include ulcers, nodular lesions, and whitish petechiae. Prognosis is often poor, which highlights the need for early consideration of this entity in immunocompromised patients and prompt diagnostic evaluation given the absence of specific presenting features. This review summarizes susceptible host categories, the clinical spectrum of gastrointestinal cryptococcosis, diagnostic approaches, treatment considerations, and reported outcomes.
PURPOSE:Current predictive biomarkers for immune checkpoint inhibitor (ICI)-based therapy in patients with lung adenocarcinoma (LUAD) or lung squamous cell carcinoma (LUSC), such as PD-L1 protein expression or tumor mutation burden, are still suboptimal. We aim to explore immunophenotypic factors as potential biomarkers in this patient population. METHODS:Clinical, genomic, and transcriptomic data from five patient cohorts, consisting of three publicly available data and two retrospective cohorts, were included. Immune tumor microenvironment (TME) subtype and tertiary lymphoid structure (TLS) signature were evaluated using RNA expression data, and deconvolutional cellular decomposition of tumor samples was performed using the Kassandra algorithm. Survival analysis was performed using a log-rank test and multivariate Cox regression. All statistical analyses were performed using Python version 3.10. RESULTS:In total, 514 patients were included in this analysis. A minority of LUAD (40.8%) had an immune-hot phenotype, which corresponded to better overall survival (OS) and progression-free survival (PFS) than the immune-cold phenotype. TLS-high signature was also associated with a superior ICI response rate and improved PFS, even with multivariate adjustments. Increased T-cell and macrophage infiltration and trafficking were predictive of ICI response. PD-L1 status and KEAP1 or STK11 mutations did not affect the response rates but were associated with poorer OS and PFS. CONCLUSION:Dynamic and active immune recruitment, indicated by immune-hot TME and high TLS score, was predictive of ICI benefit in patients with LUAD. Further prospective studies are warranted to expand to other treatment combinations with PD-(L)1 inhibitors.
Solitary extramedullary plasmacytoma of the kidney is an exceptionally rare plasma cell neoplasm and may closely mimic renal cell carcinoma on imaging. A woman in her late 50s was incidentally found to have a left renal mass during evaluation for non-specific abdominal discomfort. Cross-sectional imaging revealed a multiloculated cystic renal lesion with enhancing walls, raising concern for primary renal malignancy. CT-guided biopsy demonstrated sheets of plasma cells with kappa light-chain restriction. Comprehensive evaluation, including serum studies, positron emission tomography-CT and bone marrow biopsy, showed no evidence of systemic multiple myeloma, confirming the diagnosis of solitary renal plasmacytoma. The patient was treated with definitive external beam radiotherapy and achieved complete radiological resolution, with no evidence of progression on follow-up. This case highlights an important diagnostic pitfall and emphasises the value of early tissue diagnosis to avoid unnecessary nephrectomy and allow curative local therapy.
Male breast cancer (MBC) accounts for 1% of all breast cancer patients. In the US, 2800 MBC new cases are diagnosed yearly. MBC patients have high mortality due to late and advanced stages at diagnosis. Understanding demographics and racial disparities in MBC is crucial, and may significantly impact morbidity and mortality. We analyzed data from the National Inpatient Sample and identified patients admitted to the hospital with MBC diagnosis in 2021 using STATA BE 18.0 software. To accurately identify metastatic disease to the bone, lung, and meninges, we excluded patients with any of these concurrent diagnoses: melanoma, primary central nervous system (CNS) tumors, and prostate and lung cancer. We investigated baseline patient characteristics and stratified the results based on race. The primary endpoint was in-hospital mortality (IHM). Length of stay (LOS) and total charge (TOTCH) were secondary endpoints. Results were adjusted for age, race, insurance type, smoking, alcohol, liver disease (LD), diabetes (DM), chronic kidney disease (CKD), and congestive heart failure (CHF). Other factors including metastases to the bone, lung, meninges, history of chest radiation, protein energy malnutrition (PEM), and palliative care utilization were also assessed and adjusted for. A total of 1,915 patients met criteria for inclusion. Of those, 75% were Caucasians,16% African Americans (AA), and 9.2% of other races. AA patients were significantly younger (mean age 64 vs. 69 years in non-AA, p<0.05), and more commonly in the lowest income quartile (49% vs. 22% for non-AA; p<0.05). Clinically, 24% had estrogen receptor-positive status, 10% had prior chest radiation, and 32% had metastatic disease (24% to the bones, 16% to lung, 11% to liver, and 5.4% to CNS). Comorbidities included smoking (40%), obesity (20%), type 2 DM (35%), coronary artery disease (27%), CHF (26%), and PEM (12%), Overall IHM was 5% with a mean 6-day LOS. Compared to non-AA, AA patients had significantly higher mortality rates (11% vs. 4 %, p<0.05) and longer LOS (9 vs 5.4 days; p< 0.05). TOTCH was higher in AA ($87,937 vs. $68,852) but did not reach significance (p=0.48). LD, CKD, and liver metastases were independent predictors of inpatient mortality. Palliative care utilization was 10% overall, and similar in both races (AA-16% vs non-AA 10%, p=0.15). Significant socio-economic and racial disparities impact MBC outcomes, with AA patients presenting at younger ages, experiencing longer LOS, and higher mortality rates. The high prevalence of comorbidities and metastatic disease at presentation highlights the need for earlier detection through screening and education programs, and for interventions to address racial disparities, namely in AA patients. Future research should focus on understanding potential barriers underlying these disparities, to develop strategies to mitigate them. Raj Shah, Anas Alqam, Elie Chalhoub, Khalil Choucair. Inpatient outcomes and racial differences in male breast cancer: insights from the 2021 National Inpatient Sample [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4970.
