Immune checkpoint inhibitors targeting PD-1/PD-L1 in the treatment of human lymphomas.

Non-Hodgkin lymphomas (NHLs) encompass a diverse group of malignancies arising from B cells, T cells, and natural killer (NK) cells at various stages of differentiation. Conversely, classical Hodgkin lymphomas (cHLs) primarily feature Reed-Sternberg cells (RSCs) amid a background of reactive immune cells. Immunomodulatory pathways, notably the PD-1/PD-L1 axis, play pivotal roles in tumor immune evasion across both NHLs and cHLs. Elevated expression of PD-1 and PD-L1 is observed in a spectrum of lymphomas, influencing prognosis and treatment response. Therapeutically, immune checkpoint inhibitors (ICIs) targeting PD-1/PD-L1 have revolutionized lymphoma management, particularly in relapsed/refractory cases. Nivolumab and pembrolizumab, among others, have demonstrated efficacy in various B-cell lymphomas, with promising outcomes in cHL. Combination strategies incorporating ICIs with conventional chemotherapy or targeted agents show enhanced efficacy and are being explored extensively. In this review we discuss the most important features of the tumor microenvironment of NHLs and cHLs, address the therapeutic approaches with ICIs and try to outline future perspectives.

Remission With Radiation Therapy in Primary Tongue Mucosa-Associated Lymphoid Tissue Lymphoma: A Case Report.

Mucosa-associated lymphoid tissue (MALT) lymphoma arising from the tongue is a rare pathologic condition for which a standard treatment mode has not been established. This disease represents a low-grade lymphoma frequently found in the stomach but rarely in the lymphoid tissue of the tongue. Only six cases that have been reported could be retrieved. We present the case of a 79-year-old woman who manifested with a mass on her tongue. A biopsy of the mass confirmed a diagnosis of MALT lymphoma. Radiation therapy of 30.6 Gy in 17 fractions was performed, and a complete metabolic response was achieved.

Sex-based Differences in Risk for Therapy-related Myeloid Neoplasms.

BACKGROUND: Therapy-related myeloid neoplasm (t-MN) is a life-threatening complication of autologous peripheral blood stem cell (PBSC) transplantation for non-Hodgkin lymphoma (NHL). Prior studies report an association between clonal hematopoiesis (CH) in PBSC and risk of t-MN, but small samples precluded examination of risk within specific sub-populations. METHODS: Targeted DNA sequencing was performed to identify CH mutations in PBSC from a retrospective cohort of 984 NHL patients (median age at transplant 57y; range: 18-78). Fine-Gray proportional subdistribution hazard regression models estimated association between number of CH mutations and t-MN, adjusting for demographic, clinical, and therapeutic variables. Secondary analyses evaluated association between CH and t-MN among males and females. RESULTS: CH was identified in PBSC from 366 patients (37.2%). t-MN developed in 60 patients after median follow-up of 5y. Presence of ≥2 mutations conferred increased t-MN risk (adjusted hazard ratio [aHR]=2.10, 95% confidence interval [CI]=1.08-4.11, p=0.029). CH was associated with increased t-MN risk among males (aHR=1.83, 95%CI=1.01-3.31) but not females (aHR=0.56, 95%CI=0.15-2.09). Although prevalence and type of CH mutations in PBSC was comparable, the 8y cumulative incidence of t-MN was higher among males vs. females with CH (12.4% vs. 3.6%) but was similar between males and females without CH (4.9% vs. 3.9%). Expansion of CH clones from PBSC to t-MN was seen only among males. CONCLUSIONS: Presence of CH mutations in PBSC confers increased risk of t-MN after autologous transplantation in male but not female patients with NHL. Factors underlying sex-based differences in risk of CH progression to t-MN merit further investigation.

Secular trends in incidence and mortality of non-Hodgkin's lymphoma in China, 1990-2019, and predictions to 2030: Outlook for the future burden of disease.

BACKGROUND: The aim of this study was to analyze the trend of non-Hodgkin's lymphoma incidence and mortality in China from 1990 to 2019, along with assessing the effects of age, period, and cohort, as well as to predict future trends. MATERIAL AND METHODS: Using data from the Global Burden of Disease Study 2019 we calculated the estimated annual percentage changes in the incidence and mortality of non-Hodgkin's lymphoma. Age-period-cohort analysis was used to assess the independent effects of these elements. Incidence and mortality until 2030 were predicted using a Bayesian age-period-cohort approach. RESULTS: During 1990-2019, there was a significant increase in the age-standardized incidence and mortality rate in non-Hodgkin's lymphoma. Strong effects of birth cohort and period on non-Hodgkin's lymphoma incidence and mortality were observed. In terms of prediction, future non-Hodgkin's lymphoma incidence and mortality in China will continue to increase, while the mortality rate will decrease; for women, both the rates are projected to rise, but they will remain lower than men. CONCLUSIONS: Currently, the non-Hodgkin's lymphoma burden is high in China, and it is expected to continue increasing in the future. Policymakers need to prioritize addressing the factors contributing to sex differences in disease burden, including variations in environmental exposures and lifestyles among men and women.

Reduced-intensity conditioning with fludarabine/busulfan versus fludarabine/low-dose melphalan in patients with non-Hodgkin lymphoma undergoing allogeneic haematopoietic stem cell transplantation.

Reduced-intensity conditioning regimens are commonly used in allogeneic haematopoietic cell transplantation for non-Hodgkin lymphoma (NHL); however, the optimal regimen remains unknown. In this study, the outcomes of adult patients with NHL who received fludarabine plus reduced-dose busulfan (6.4 mg/kg; Flu/Bu2) (n = 286) and fludarabine plus low-dose melphalan (80 or 100 mg/m2; Flu/Mel80-100) (n = 283) between January 2009 and December 2020 were compared using Japanese registry data. The primary end-point was the 5-year overall survival (OS). The 5-year OS was 53.8% (95% CI, 47.6-59.6) and 42.4% (95% CI, 35.6-49.0) in the Flu/Bu2 and Flu/Mel80-100 groups respectively (p = 0.030). After inverse probability of treatment weighting adjustment, the adjusted HR of Flu/Bu2 compared with Flu/Mel80-100 group for 5-year OS was 0.77 (95% CI, 0.60-0.99, p = 0.046), 0.97 (95% CI, 0.78-1.21, p = 0.798) for 5-year progression-free survival, 0.65 (95% CI, 0.45-0.94, p = 0.022) for 5-year cumulative risk of non-relapse mortality and 1.25 (95% CI, 0.95-1.64, p = 0.115) for 5-year cumulative risk of relapse. In this study, patients with NHL who received Flu/Bu2 were associated with better OS and lower non-relapse mortality than those who received Flu/Mel80-100.

Clinical study of chemotherapy-related cognitive impairment in patients with non-Hodgkin lymphoma.

BACKGROUND: Chemotherapy for malignant tumors can cause brain changes and cognitive impairment, leading to chemotherapy-induced cognitive impairment (CICI). Current research on CICI has focused on breast cancer and Hodgkin's lymphoma. Whether patients with non-Hodgkin's lymphoma (NHL) undergoing chemotherapy have cognitive impairment has not been fully investigated. AIM: To investigate whether NHL patients undergoing chemotherapy had cognitive impairments. METHODS: The study included 100 NHL patients who were required to complete a comprehensive psychological scale including the Brief Psychiatric Examination Scale (MMSE) at two time points: before chemotherapy and within 2 wk of two chemotherapy courses. A language proficiency test (VFT), Symbol Number Pattern Test (SDMT), Clock Drawing Test (CDT), Abbreviated Daily Cognition Scale (ECog-12), Prospective and Retrospective Memory Questionnaire, and Karnofsky Performance Status were used to assess cognitive changes before and after chemotherapy. RESULTS: The VFT scores for before treatment (BT) and after treatment (AT) groups were 45.20 ± 15.62, and 42.30 ± 17.53, respectively (t -2.16, P < 0.05). The CDT scores were 8 (3.5-9.25) for BT and 7 (2.5-9) for AT groups (Z -2.1, P < 0.05). Retrospective memory scores were 13.5 (9-17) for BT and 15 (13-18) for AT (Z -3.7, P < 0.01). The prospective memory scores were 12.63 ± 3.61 for BT and 14.43 ± 4.32 for AT groups (t -4.97, P < 0.01). The ECog-12 scores were 1.71 (1.25-2.08) for BT and 1.79 (1.42-2.08) for AT groups (Z -2.84, P < 0.01). The SDMT and MMSE values did not show a significant difference between BT and AT groups. CONCLUSION: Compared to the AT group, the BT group showed impaired language, memory, and subjective cognition, but objective cognition and execution were not significantly affected.

Non-Hodgkin's Anaplastic Large T-Cell Lymphoma: A Case Report.

Anaplastic large T/null cell lymphoma (ALCL) is an aggressive non-Hodgkin's lymphoma (NHL) that most commonly affects young men. Herein, we present a case of a 32-year-old male patient in severe condition with ulcerated right axillary adenopathy, diffuse subcutaneous nodules, and sepsis. He was admitted to the ED, where a bone marrow aspirate and biopsy confirmed the diagnosis of ALCL. The immunohistochemical examination demonstrated neoplastic cells with immunopositivity with antibodies CD3 (focal), CD30 (diffuse), protein ALK-1 (diffuse), and epithelial membrane antigen (EMA) (multifocal). Appropriate chemotherapy treatment was done, and the patient showed a complete response. This article aims to report a rare subtype of NHL to increase awareness and bring up a discussion about the clinical presentation and diagnostic features of ALCL. Moreover, we discuss treatment regimens that are currently used and have shown reasonable disease remission rates.

Exploring the Health Benefits of Boletus aereus Polysaccharides: Extraction, Structural Characterization, and Antiproliferative Properties against Non-Hodgkin's Lymphomas (NHLs).

Boletus aereus Fr. ex Bull. stands out as a delectable edible mushroom with high nutritional and medicinal values, featuring polysaccharides as its primary nutrient composition. In our continuous exploration of its beneficial substances, a novel polysaccharide (BAPN-1) with a molecular weight of 2279 kDa was prepared. It was identified as a glucan with a backbone composed of the residues →4)-α-Glcp-(1→ and →4,6)-α-Glcp-(1→ connected in a proportion of 5:1 and a ß-Glcp-(1→ side residue attached at C6 of the →4,6)-α-Glcp-(1→ residue. Biologically, BAPN-1 exhibited broad-spectrum antiproliferative activities against various NHL cells, including HuT-78, OCI-LY1, OCI-LY18, Jurkat, RL, and Karpas-299, with IC50 values of 0.73, 1.21, 3.18, 1.52, 3.34, and 4.25 mg/mL, respectively. Additionally, BAPN-1 significantly induced cell cycle arrest in the G2/M phase and caused apoptosis of NHL cells. Mechanistically, bulk RNA sequencing and Western blot analysis revealed that BAPN-1 could upregulate cyclin B1 and enhance cleaved caspase-9 expression through the inhibition of FGFR3 and RAF-MEK-ERK signaling pathways. This work supports the improved utilization of B. aereus in high-value health products.

Understanding the interplay between chronic lymphocytic leukemia and type 2 diabetes.

INTRODUCTION: Comorbidities play an important role in the management of chronic lymphocytic leukemia (CLL) and may influence survival and treatment outcomes. Considering the aging general population and increasing incidence of type 2 diabetes (T2D), a comprehensive understanding of the interplay between CLL and T2D is essential for optimizing care and outcomes. AREAS COVERED: We present current knowledge on co-existing CLL and T2D including prevalence, shared etiology and risk factors and how the conditions and treatment hereof may influence the outcome of one another. A literature search was performed using PubMed with the cutoff date on 1 February 2024. EXPERT OPINION: The increased mortality observed in persons with CLL who have co-existing T2D is partially ascribed to infections, prompting physicians managing individuals with both conditions to consider closer monitoring during instances of infection and individualized prophylaxis. People with CLL and T2D should be managed for CLL in accordance with the international working group on CLL criteria, and we recommend that physicians exercise particular care not to delay treatment for these individuals. Multidisciplinary approaches with involvement of several specialties may be required for optimal supportive care of co-occurring T2D and CLL.

Effective geriatric management strategies for fatal non-Hodgkin lymphoma: Insights from a case report. / Estrategias geriátricas efectivas para el tratamiento del linfoma no Hodgkin mortal: conclusiones de un estudio de caso.

This case report delves into the intricate medical history of an 85-year-old male who experienced a myriad of health challenges throughout his years. With a medical history full of conditions, such as stroke, sinus bradycardia, chronic obstructive pulmonary disease, severe pulmonary hypertension, and chronic gastritis, the patient´s health profile is further complicated by prostatic hypertrophy, persistent dorsalgia and lumbalgia, the presence of a thyroid nodule, and a recent onset of hypothyroidism. Among the diverse medical conditions of this patient, our narrative is primarily centered on his latest diagnosis: non-Hodgkin´s lymphoma. Non-Hodgkin´s lymphoma is not just a mere addition to his already complex medical history; it is a malignant neoplasm that shapes worldwide patterns of cancer mortality. The first indicators that led to this discovery were the patient´s complaints of persistent pain in the left lateral neck region associated with dysphagia. This was not an isolated symptom; the patient also reported a month-long history of asthenia, myalgias, weakness around the pelvic girdle, fatigue, and hyporexia, depicting a concerning clinical picture. Advanced diagnostic tools, namely ultrasound and computed tomography, shed light on submaxillary and cervical adenopathies. To corroborate such findings and get a definitive diagnosis of malignancy, a fine-needle aspiration was advised. Through this case, we aim not only to describe a clinical scenario but to highlight the challenges involved in the diagnosing and treatment of non-Hodgkin ´s lymphoma, especially in elderly patients. The overlap of multiple comorbidities adds further complexity to the scene, demanding meticulous care and expertise. This report serves as an educational tool for oncology experts, as well as testimony to the complexities of patient care in the oncology diagnostic and treatment setting.

Este reporte de caso se centra en el intricado historial médico de un varon de 85 años que experimenta una miriada de problemas de salud a lo largo de sus años. Con un historial médico lleno de afecciones, como accidente cerebrovascular, bradicardia sinusal, enfermedad pulmonar obstructiva crónica, hipertensión pulmonar grave y gastritis crónica, el perfil de salud del paciente se complica aún más por la presencia de hipertrofia prostática, dorsalgia y lumbalgia persistentes, la presencia de un nódulo tiroideo y el reciente diagnóstico de hipotiroidismo. Entre las diversas afecciones de este paciente, nuestra narración se centra principalmente en su último diagnóstico: linfoma no Hodgkin. El linfoma no hodgkiniano no es un mero añadido a su ya complejo historial médico; es una neoplasia maligna que configura las tendencias de mortalidad por cáncer a nivel mundial. Los primeros indicadores que llevaron a este descubrimiento fueron las quejas del paciente por dolor persistente en la región lateral izquierda del cuello, asociado a disfagia. No se trataba de un síntoma aislado, ya que el paciente también refería desde hacía un mes astenia, mialgias, debilidad alrededor de la cintura pélvica, fatiga e hiporexia, lo que describía un cuadro clínico preocupante. Las herramientas diagnósticas avanzadas, a saber, la ecografía y la tomografía computarizada, arrojaron luz sobre las adenopatías submaxilares y cervicales. revelaron sobre las adenopatías submaxilares y cervicales.

Current landscape of CD3 bispecific antibodies in hematologic malignancies.

Over the past 30 years the incorporation of monoclonal antibody (mAb) treatments into the management of hematologic malignancies has led to significant improvements in patient outcomes. The key limitation of mAb treatments is the necessity for target antigen presentation on major histocompatibility complex (MHC) and costimulatory molecules to elicit a cytotoxic immune response. With the advent of bispecific antibodies (BsAbs), these limitations can be overcome through direct stimulation of cytotoxic T cells, thus limiting tumor cell evasion. BsAbs are rapidly being incorporated into treatment regimens for hematologic malignancies, and there are now seven FDA-approved treatments in this class, six of which have been approved in the past year. In this review we describe the function, complications, and clinical trial data available for CD3 BsAbs in the treatment of lymphoma, myeloma, and leukemia.

Intratumoral T-cell composition predicts epcoritamab-based treatment efficacy in B-cell non-Hodgkin lymphomas.

Leveraging endogenous tumor-resident T-cells for immunotherapy using bispecific antibodies (BsAb) targeting CD20 and CD3 has emerged as a promising therapeutic strategy for patients with B-cell non-Hodgkin lymphomas. However, features associated with treatment response or resistance are unknown. To this end, we analyzed data from patients treated with epcoritamab-containing regimens in the EPCORE NHL-2 trial (NCT04663347). We observed downregulation of CD20 expression on B-cells following treatment initiation both in progressing patients and in patients achieving durable complete responses (CR), suggesting that CD20 downregulation does not universally predict resistance to BsAb-based therapy. Single-cell immune profiling of tumor biopsies obtained following one cycle of therapy revealed substantial clonal expansion of cytotoxic CD4+ and CD8+ T-cells in patients achieving CR, and an expansion of follicular helper and regulatory CD4+ T-cells in patients whose disease progressed. These results identify distinct tumor-resident T-cell profiles associated with response or resistance to BsAb therapy.

Diagnosis and treatment of secondary nephrotic syndrome with rash as the first symptom: a case report.

BACKGROUND: Membranous nephropathy (MN) is a common type of nephrotic syndrome (NS) in adults, accounting for about 20-30% of cases. Although secondary to specific factors, the coexistence of MN and mantle cell lymphoma (MCL) has been scarcely reported in clinical literature. CASE PRESENTATION: A 59-year-old Chinese male was admitted to the hospital with a generalized pruritic rash with bilateral lower extremity edema, which did not improve significantly after symptomatic treatment. He had undergone renal biopsy, and the diagnosis was thought to be secondary MN (SMN), therefore, we did a lymph node biopsy on the patient and found that MN was complicated with MCL. Soon after, the patient was admitted to the hematology department for a BR chemotherapy regimen (composed of bendamustine 90 mg/m2 BSA (body surface area), rituximab 375 mg/m2 BSA and dexamethasone 5 mg), and during the post-treatment follow-up, both his symptoms and renal function improved. CONCLUSIONS: The mechanism underlying the combination of SMN and MCL remains elusive and exceedingly rare, consequently often overlooked in clinical practice. This case serves to offer valuable clinical insights for diagnosis and treatment, while emphasizing the pivotal role of renal pathology in clinical assessment.

Diffuse large B-cell lymphoma in the uterus with unexpected manifestations: a case report.

BACKGROUND: Lymphoid neoplasm is a common disease, arising from lymphoid cells. It is divided into Hodgkin lymphoma and non-Hodgkin lymphoma. Non-Hodgkin lymphoma can be intranodular or extranodular, which happens in 25% of primary cases. The most common locations of extranodular non-Hodgkin lymphoma are the skin and gastrointestinal tract. The genital tract is a rare location; most lymphomas arise from the cervix and vagina, while the uterine corpus is an extremely rare location. In our case, the patient was diagnosed with primary extranodular non-Hodgkin lymphoma in different locations of her genital tract. CASE PRESENTATION: A 48-year-old nonparous Syrian woman complained of diffuse abdominal pain, fatigue, debility, high fever, vomiting, and urinary retention for a week. The last menstrual period of the patient was 5 years previously. The physical examination showed periodic abdominal pain with severe fatigue and increased abdominal size. The laboratory investigations were within normal limits except for a low level of hemoglobin and a high level of cancer antigen 125. The radiological investigations showed a uterine sizable lobulated mass with irregular borders and high and heterogeneous density, extending to the right and left ovaries, enlargement lymph nodes around the abdominal aortic and right iliac vessels, and severe right pleural effusion with right inferior lobe atelectasis. A total hysterectomy and oophorectomy were done. The histopathological examination showed that the patient had non-Hodgkin lymphoma (primary tumor). CONCLUSION: Primary non-Hodgkin lymphoma in the female genital tract is an extremely rare disease. Fast diagnosis and treatment can improve the outcomes, so this differential diagnosis should be in our minds even in the absence of systematic manifestations of lymphoma. More studies are needed to explain the pathology of this disease and to put guidelines that determine the perfect methods for diagnosis and treatment.

Insight into Mantle Cell Lymphoma Pathobiology, Diagnosis, and Treatment Using Network-Based and Drug-Repurposing Approaches.

Mantle cell lymphoma (MCL) is a rare, incurable, and aggressive B-cell non-Hodgkin lymphoma (NHL). Early MCL diagnosis and treatment is critical and puzzling due to inter/intra-tumoral heterogeneity and limited understanding of the underlying molecular mechanisms. We developed and applied a multifaceted analysis of selected publicly available transcriptomic data of well-defined MCL stages, integrating network-based methods for pathway enrichment analysis, co-expression module alignment, drug repurposing, and prediction of effective drug combinations. We demonstrate the "butterfly effect" emerging from a small set of initially differentially expressed genes, rapidly expanding into numerous deregulated cellular processes, signaling pathways, and core machineries as MCL becomes aggressive. We explore pathogenicity-related signaling circuits by detecting common co-expression modules in MCL stages, pointing out, among others, the role of VEGFA and SPARC proteins in MCL progression and recommend further study of precise drug combinations. Our findings highlight the benefit that can be leveraged by such an approach for better understanding pathobiology and identifying high-priority novel diagnostic and prognostic biomarkers, drug targets, and efficacious combination therapies against MCL that should be further validated for their clinical impact.

Pattern of Clinical Presentation in Patients With Lymphoma.

Introduction Lymphomas take place when cells of the lymphatic system divide and re-divide in an uncontrolled fashion, and lymphomas have been termed as a "diverse group" of cancer, playing a major role in the area of oncology. The clinical behavior and manifestations of lymphomas in the head and neck region usually lack specific characteristics that would enable attribution to a specific lymphoma entity without biopsy and histological evidence. This study aimed to determine the frequency of common clinical features among patients with lymphoma. Methods This descriptive cross-sectional study was conducted at the Department of General Medicine, Lady Reading Hospital, Peshawar, from October 28, 2021 to April 28, 2022. The inclusion criteria consisted of individuals who were recently diagnosed with lymphoma and were between the ages of 10 and 50, regardless of their gender. This study enrolled a total of 186 patients diagnosed with lymphoma and assessed for common signs and symptoms. The data-gathering process included in-depth interviews, evaluations of medical history, physical exams, and initial investigations. The data analysis was done using IBM SPSS Statistics for Windows, Version 20.0 (Released 2011; IBM Corp., Armonk, New York, United States). Results The mean age of the patients was 34.5±9.6 years. Out of the total, 115 (61.8%) were men and 71 (38.2%) were women. With regard to symptoms, 134 (72%) had a fever, 80 (43%) had abdominal pain, 102 (54.8%) had vomiting, 49 (26.3%) had a headache, 111 (59.7%) had weight loss, and 17 (9.1%) had a cough. With regard to signs, 33 (17.7%) had painless lymphadenopathy, 58 (31.2%) had jaundice, 157 (84.4%) had anemia, 147 (79%) had hepatomegaly, 160 (86%) had splenomegaly, 24 (12.9%) had ascites, and 16 (8.6%) had abdominal tenderness. Conclusion The varied clinical appearance of lymphoma makes treatment difficult. In severe cases of lymphoma, early and timely diagnosis is crucial for proper and prompt treatment. The signs and symptoms, along with demographic information of patients, thorough medical history, imaging testing, and clinical examination, may indicate lymphoma.

Real-world outcomes with novel therapies in relapsed/refractory diffuse large B-cell lymphoma.

This study used COTA de-identified data (2010-2021) of patients in the US to explore outcomes of novel therapies in relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) in real-world settings. Demographics, clinical characteristics, and clinical outcomes of patients with R/R DLBCL who received novel treatments including chimeric antigen receptor T-cell (CAR T) therapy and tafasitamab- or polatuzumab-based therapies were evaluated. Overall, 175 patients with R/R DLBCL were analyzed; 73, 69, and 27 received CAR T therapy, polatuzumab-based regimens, and tafasitamab-based regimens, respectively. In patients who had ≥1 prior lines of therapy (i.e. starting second-line or later therapy; 2 L+), CAR T, polatuzumab-based regimens, and tafasitamab-based regimens achieved a median overall survival of 26.5, 7.8, and 6.3 months, respectively. Outcomes were particularly poor for patients with relapse following CAR T, indicating that polatuzumab- and tafasitamab-based regimens in 2 L + R/R DLBCL have suboptimal outcomes in the real world. Additional treatment options are needed.

Mitigating infection risks: The promise and challenge of bispecific antibodies in haematological malignancies.

Bispecific antibodies have shown significant clinical efficacy in patients with relapsed/refractory B-cell non-Hodgkin lymphomas and multiple myeloma, expanding treatment options for these patients. While these advancements are promising, it is important to be aware of associated side effects, such as cytokine release syndrome, neutropenia and infections. Gonugunta et al. provide valuable insights into the infection risks linked to the use of bispecific antibodies in haematological malignancies, drawing on both clinical trial data and real-world experiences. Commentary on: Gonugunta et al. Risk of infections with bispecific antibodies in B-cell non-Hodgkin lymphomas and multiple myeloma-The current state. Br J Haematol 2024 (Online ahead of print). doi: 10.1111/bjh.19633.

Optimization and characterization of Rituximab targeted multidrug loaded cyclodextrin nanoparticles against Non-Hodgkin Lymphoma.

Currently, Non-Hodgkin Lymphoma (NHL) constitutes 85-90 % of all lymphomas. Clinical treatment of NHL is based on the "4-drug regimen" known as CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone). Rituximab (RTX) is added to increase the effectiveness and selectivity of the treatment and is the first-line standard treatment for NHL patients. However, success is often prevented by the development of drug resistance. In this study, it was aimed to overcome drug resistance by using two novel tumor-targeted derivatives: guanidine-amphiphilic cyclodextrin (ACD) and guanidine-cyclodextrin polymer (PCD) nanoparticles (NP). These constructs display promise in overcoming drug resistance and enhancing the effectiveness of R-CHOP treatment while potentially eliminating the need for corticosteroid. NP were found to be smaller than 200 nm by dynamic light scattering (DLS). Hemolytic activity and cytotoxicity data on L929 cells demonstrated the safety of the newly synthesized CD derivatives. Additional in vitro characterization studies, including surface charge, physical stability, drug loading capacity, drug release profile, and imaging, as well as conventional and 3D cell culture studies were carried out. Compared to drug solutions, the viability of Daudi human lymphoma cells was statistically significantly decreased in both drug-loaded ACD and PCD NP formulations (p < 0.05). Additionally, RTX-conjugated and drug-loaded ACD NPs exhibited the lowest cell viability due to RTX dependent cytotoxicity.

Subsequent Malignancies After CD19-Targeted Chimeric Antigen Receptor T Cells in Patients With Lymphoma.

Chimeric antigen receptor (CAR) T cells are an established treatment for B cell non-Hodgkin lymphomas (B-NHL). With the remarkable success in improving survival, understanding the late effects of CAR T cell therapy is becoming more relevant. The aim of this study is to determine the incidence of subsequent malignancies in adult patients with B-NHL. We retrospectively studied 355 patients from 2 different medical centers treated with four different CAR T cell products from 2016 to 2022. The overall cumulative incidence for subsequent malignancies at 36 months was 14% (95% CI: 9.2%, 19%). Subsequent malignancies were grouped into 3 primary categories: solid tumor, hematologic malignancy, and dermatologic malignancy with cumulative incidences at 36 months of 6.1% (95% CI: 3.1%-10%), 4.5% (95% CI: 2.1%-8.1%) and 4.2% (95% CI: 2.1%-7.5%) respectively. Notably, no cases of T cell malignancies were observed. In univariable analysis, increasing age was associated with higher risk for subsequent malignancy. While the overall benefits of CAR T products continue to outweigh their potential risks, more studies and longer follow ups are needed to further demonstrate the risks, patterns, and molecular pathways that lead to the development of subsequent malignancies.