Metabolic tumor volume and the survival of patients with Non-Hodgkin lymphoma treated with chimeric antigen receptor T cell therapy: a meta-analysis.

Background: Chimeric antigen receptor T cell (CAR-T) is a promising treatment for aggressive Non-Hodgkin lymphoma (NHL). The aim of the meta-analysis was to determine the association between metabolic tumor volumes (MTV) derived on positron emission tomography before CAR-T infusion and the survival of patients with NHL. Methods: Relevant observational studies pertaining to the purpose of the meta-analysis were obtained through a search of PubMed, Web of Science, and Embase from inception of the databases to April 1, 2024. The data was combined using a random-effects model that accounted for the potential influence of between-study heterogeneity. Results: Fifteen observational studies were included. Pooled results showed that compared to those with a lower MTV, the NHL patients with a higher MTV before CAR-T infusion were associated with a poor progression-free survival (hazard ratio [HR]: 1.73, 95% confidence interval [CI]: 1.48 to 2.02, p < 0.001; I2 = 20%) and overall survival (HR: 2.11, 95% CI: 1.54 to 2.89, p < 0.001; I2 = 58%). Subgroup analysis showed that the association between MTV and survival of NHL patients after CAR-T was not significantly impacted by study design, methods for determination of MTV cutoff, or analytic models (univariate or multivariate, p for each subgroup all < 0.05). Subgroup analysis suggested a stronger association between MTV and poor survival outcomes in patients with median of lines of previous treatment of 2 or 3 as compared to those of 4 (p for subgroup difference < 0.05). Further meta-regression analyses suggested that the association between MTV and survival was not significantly affected by sample size, age, proportion of men, cutoff value of MTV, follow-up duration, or study quality scores (p all > 0.05). Conclusion: A high MTV at baseline is associated with a poor survival of NHL patients after CAR-T. Systematic Review Registration: https://inplasy.com/, identifier INPLASY (INPLASY202450069).

Toward Inclusive Oncology: Challenges in the Therapy of Pediatric Non-B Non-Hodgkin Lymphomas.

BACKGROUND/AIM: Non-B non-Hodgkin lymphomas (NHL) represent over 30 T/NK lymphoma types. The majority of them are T-cell lymphoblastic lymphomas (TLL) and anaplastic large cell lymphomas (ALCL). Other rare non-B NHLs represent a diverse group of neoplasms, usually excluded from clinical trials. This study analyzed outcomes in pediatric patients with non-B NHL in a single oncology center with particular emphasis on patients with rare NHLs. PATIENTS AND METHODS: We retrospectively analyzed data from patients <18 years with newly diagnosed non-B NHL treated at the Department of Pediatric Hematology and Oncology in Bydgoszcz between 2002 and 2022. The probability of 5-year overall survival (pOS) and event-free survival (pEFS) were calculated for the entire cohort and patients with TLL and ALCL. The clinical course for patients with rare non-B NHL was described in detail. RESULTS: Twenty-six children were eligible for analysis. Fourteen patients were diagnosed with ALCL, nine with TLL, and three with rare NHL types (subcutaneous panniculitis-like T-cell lymphoma, extranodal NK/T-cell lymphoma and hydroa vacciniforme-like lymphoproliferative disease associated lymphoma). For the entire group, the 5-year pOS was 83.7% and the 5-year pEFS was 72.4%. For TLL and ALCL, the outcomes were comparable with those achieved in clinical trials. Patients with rare NHL were treated according to individualized therapy recommendations based on physicians' expertise and available case report descriptions. CONCLUSION: There is a lack of knowledge on optimal therapeutic strategies for rare NHLs. It is crucial to create trials dedicated to uncommon NHLs and establish therapy guidelines for these patients.

An update on the minimally invasive diagnosis of lymphoma for the chest physicians.

Mediastinal lymphadenopathy has a broad differential diagnosis which includes lymphoma. The current preferred biopsy technique for mediastinal lymph nodes is transbronchial needle aspiration which has mixed results in terms of sensitivity, specificity and diagnostic yields; there are also limitations with subtyping lymphomas with needle aspiration alone which can be a barrier to determine management strategies. Invasive mediastinal lymph node sampling such was with mediastinoscopy provides higher yields and preserved lymph node architecture for both diagnosis and subtyping of lymphoma but carries a higher risk of morbidity and complications. Novel techniques that may increase the diagnostic yield of bronchoscopy in the diagnosis of lymphoma are core biopsy needles, intranodal forcep biopsy, and intranodal cryobiopsy. The evidence is limited due to a relatively small number of cases, so further research is needed to standardize best practices for the bronchoscopic diagnosis of lymphoma. Pleural effusions in lymphoma can be present in up to 30 % of cases with the majority being non-Hodgkins's lymphoma. The presence of exudative effusion in the setting of an existing or prior diagnosis of lymphoma should raise clinical suspicions. Other less common subtypes of lymphoma presenting as primary pleural effusions are explored as well.

Non-Hodgkin lymphoma presenting with spinal cord compression: A population-based analysis of the NHL-BFM study group.

BACKGROUND: Spinal cord compression is a rare presentation of non-Hodgkin lymphoma (NHL) in children. We aimed to describe the prevalence, histological subtypes, clinical presentation, therapy, and outcome of those children in a population-based cohort. The chemotherapy regimen remained comparable over time. METHODS: We retrospectively identified all children and adolescents with paresis as initial manifestations of the NHL between January 1990 and December 2020 from the NHL-BFM database. Characteristics, therapy, and outcome data were gathered from the database and patient files. RESULTS: Fifty-seven of 4779 children (1.2%) presented with initial paresis due to spinal cord compression. The median age was 10.3 years (range, 3.1-18.0 years), and 33% were female. Initial symptoms were paresis/weakness (n = 50, 88%), back pain (n = 33, 58%), paresthesia (n = 23, 40%), and bladder dysfunction and/or constipation (n = 22, 39%), persisting for a median of 14 days before diagnosis. Subtype distribution was mature B-NHL (n = 41, 72%), precursor B-lymphoblastic lymphoma (LBL) (n = 12, 21%), anaplastic large cell lymphoma (ALCL) (n = 3, 5%), and T-LBL (n = 1, 2%). Initial emergency therapy included surgery (70%) and/or chemotherapy/steroids (63%). Five-year event-free survival and overall survival (80% ± 5% and 82% ± 5%, respectively) were comparable with all other NHL patients. Neurological symptoms persisted in approximately one-third of surviving patients at the last follow-up. CONCLUSION: 1.2% of pediatric NHL patients presented with paresis from spinal cord compression mainly due to B-cell lymphomas. Neurological sequelae were observed in one-third of surviving patients.

Survival trend and outcome prediction for pediatric Hodgkin and non-Hodgkin lymphomas based on machine learning.

Pediatric Hodgkin and non-Hodgkin lymphomas differ from adult cases in biology and management, yet there is a lack of survival analysis tailored to pediatric lymphoma. We analyzed lymphoma data from 1975 to 2018, comparing survival trends between 7,871 pediatric and 226,211 adult patients, identified key risk factors for pediatric lymphoma survival, developed a predictive nomogram, and utilized machine learning to predict long-term lymphoma-specific mortality risk. Between 1975 and 2018, we observed substantial increases in 1-year (19.3%), 5-year (41.9%), and 10-year (48.8%) overall survival rates in pediatric patients with lymphoma. Prognostic factors such as age, sex, race, Ann Arbor stage, lymphoma subtypes, and radiotherapy were incorporated into the nomogram. The nomogram exhibited excellent predictive performance with area under the curve (AUC) values of 0.766, 0.724, and 0.703 for one-year, five-year, and ten-year survival, respectively, in the training cohort, and AUC values of 0.776, 0.712, and 0.696 in the validation cohort. Importantly, the nomogram outperformed the Ann Arbor staging system in survival prediction. Machine learning models achieved AUC values of approximately 0.75, surpassing the conventional method (AUC = ~ 0.70) in predicting the risk of lymphoma-specific death. We also observed that pediatric lymphoma survivors had a substantially reduced risk of lymphoma after ten years b,ut faced an increasing risk of non-lymphoma diseases. The study highlights substantial improvements in pediatric lymphoma survival, offers reliable predictive tools, and underscores the importance of long-term monitoring for non-lymphoma health issues in pediatric patients.

Cinematic rendering of primary adrenal lymphoma.

Primary adrenal lymphoma (PAL) is a particularly rare subset of malignant adrenal neoplasms, accounting for ∼1% of all non-Hodgkin's lymphomas. Reported outcomes of PAL, though limited, are dismal, with a 12-month survival rate of ∼20%. PAL is treated with polychemotherapy and early tissue diagnosis to allow initiation of chemotherapy is associated with improved outcomes. Early and accurate radiological diagnosis of PAL is therefore essential in improving outcomes through informing decisions to biopsy and thereby facilitating timely initiation of chemotherapy. To date, however, imaging features of PAL have not been conclusively defined, and a range of divergent imaging appearances have been reported. Cinematic rendering (CR) is a 3D post-processing technique that simulates the propagation and interaction of photons as they pass through the imaged volume. This results in the generation of more photorealistic images that may allow for more comprehensive visualization, description and interpretation of anatomical structures. This manuscript presents the first characterization of the various CR appearances of PAL in the reported literature and provides commentary on the clinical opportunities afforded by CR in the workup of these heterogenous tumors.

A20 promoted the phagocytosis of lymphoma cells by dendritic cells from activated B-cell-like non-Hodgkin lymphoma.

Non-Hodgkin lymphoma (NHL) is a lymphoproliferative disorder derived from either B or T lymphocytes. Among NHL, activated B-cell-like (ABC) diffuse large B-cell lymphoma (DLBCL) and T cell non-Hodgkin lymphomas (T-NHL) are poor prognosis and aggressive subtypes. Macrophages are professional phagocytic cells and dendritic cells (DCs) are professional antigen-presenting cells in immune system. Doxorubicin (Dox) and Etoposide (ET) are the most effective anti-cancer drugs. A20 and CYLD are negative regulators of NF-κB-dependent functions in many cell types. Little is known about the roles of A20 and CYLD in regulating functions of DCs and macrophages from NHL. The present study, therefore, explored whether A20/CYLD expression contributes to functions of DCs and macrophages from NHL. To this end, blood samples of seventy-nine patients with ABC DLBCL and T-NHL were examined. Gene expression profile was determined by quantitative RT-PCR and immunophenotype, cell apoptosis and phagocytosis by flow cytometry. As a result, immunophenotypic analysis showed that the numbers of CD13+CD117-, CD56+CD40+ and CD23+CD40+ expressing cells were significantly elevated in ABC DLBCL cases compared to healthy individuals and T-NHL patients. Interestingly, upon treatment of Dox and ET, the phagocytosis of lymphoma cells was significantly reduced by CD11c+CD123- DCs and the percentage of CD56+ mature DCs was significantly enhanced in ABC DLBCL patients only in the presence of A20 siRNA, but not CYLD siRNA. In conclusion, ABC DLBCL patients with low A20 expression were defective in elimination of lymphoma cells by DCs and linked to killer DC expansion in circulation.

Cutaneous Perivascular Hemophagocytosis: A Report of 2 Cases With Emphasis on Clinical and Histological Features.

ABSTRACT: Cutaneous perivascular hemophagocytosis (CH) is a histological manifestation that manifests as systemic hemophagocytic syndrome, also known as hemophagocytic lymphohistiocytosis, when accompanied by fever, hepatosplenomegaly, liver dysfunction, and cytopenia, and may rarely manifest independently of hemophagocytic lymphohistiocytosis. CH typically presents as purpuric or brownish macules and patches on the extremities, abdomen, and trunks. Histopathologically, the hallmark of CH includes extravasated erythrocytes and karyorrhectic debris phagocytized by histiocytes, associated with dermal capillary ectasia, perivascular infiltration of neutrophils, nuclear dust, and histiocytes without atypia. In this study, we report 2 cases of CH encountered in routine diagnostic practice and elucidate their significant clinical and histologic features. Our first patient had leukocytoclastic vasculitis with CH in the setting of Yersinia enterocolitis, and the second case represents CH in association with non-Hodgkin lymphoma. This study highlights the importance of considering CH as a potential indicator of underlying systemic pathology, including infectious and hematological disorders, in clinical practice.

Clinical characteristics and prognostic analysis of primary extranodal non-Hodgkin lymphoma of the head and neck.

OBJECTIVE: Primary extranodal non-Hodgkin's lymphoma (PE-NHL) of the head and neck is the second common site of extranodal lymphoma, accounting for approximately one-third of all extranodal non-Hodgkin's lymphoma (E-NHL). However, in recent years, large-scale PE-NHL case studies in China and worldwide are rare and not comprehensive enough. This work analyzed the clinical manifestations, pathological features, immunophenotypes and diagnosis of PE-NHL, as well as the factors affecting the treatment and prognosis. METHODS: A retrospective study was performed on 74 patients who were diagnosed with head and neck PE-NHL and treated for the first time. The clinical manifestations, pathological features, and immunophenotypes were summarized, and the factors related to the treatment and prognosis were analyzed. RESULTS: The most common site of this disease was the Waldeyer's ring, followed by the nasal cavity. Diffuse large B-cell lymphoma was the most common type, followed by extranodal NK T-cell lymphoma nasal type. The 1-year, 2-year, and 5-year progression-free survival (PFS) rates were 76.4%, 67.9%, and 59.3%. The 1-year, 2-year, and 5-year overall survival (OS) rates were 89.4%, 85.6%, and 63.2%. ECOG score ≥ 2, Ann Arbor stage III or IV and IPI risk stratification identifying patients as the high-risk group were independent risk factors affecting the OS of patients with PE-NHL of the head and neck. CONCLUSIONS: The most common site of PE-NHL in these Chinese patients was the Waldeyer's ring, but the incidence in the nasal cavity was higher than that reported in Western countries. Radiotherapy combined with chemotherapy had better efficacy than chemotherapy alone, and the prognosis depended on the ECOG score and clinical stage. IPI had a better prognostic value in patients in the high-risk group of head and neck PE-NHL.

Targeting the tumor microenvironment in primary central nervous system lymphoma: Implications for prognosis.

Primary central nervous system lymphoma (PCNSL) is a rare extranodal non-Hodgkin lymphoma, and there is limited research on its tumor microenvironment (TME). Nevertheless, more and more studies have evidence that TME has essential effects on tumor cell proliferation, immune escape, and drug resistance. Thus, it is critical to elucidate the role of TME in PCNSL. The understanding of the PCNSL TME is gradually unfolding, including factors that distinguish it from systemic diffuse large B-cell lymphoma (DLBCL). The TME in PCNSL exhibits both transcriptional and spatial intratumor heterogeneity. Cellular interactions between tumor cells and stroma cells reveal immune evasion signaling. The comparative analysis between PCNSL and DLBCL suggests that PCNSL is more likely to be an immunologically deficient tumor. In PCNSL, T cell exhaustion and downregulation of macrophage immune function are accompanied by suppressive microenvironmental factors such as M2 polarized macrophages, endothelin B receptor, HLA depletion, PD-L1, and TIM-3. MMP-9, Integrin-ß1, and ICAM-1/LFA-1 play crucial roles in transendothelial migration towards the CNS, while CXCL13/CXCR5, CD44, MAG, and IL-8 are essential for brain parenchymal invasion. Further, macrophages, YKL-40, CD31, CD105, PD-1/PD-L1 axis, osteopontin, galectin-3, aggregative perivascular tumor cells, and HLA deletion may contribute to poor outcomes in patients with PCNSL. This article reviews the effect of various components of TME on the progression and prognosis of PCNSL patients to identify novel therapeutic targets.

[Effect of L-Type Amino Acid Transporter 1 Expression on Clinicopathological Features and Prognosis of Non-Hodgkin's Lymphoma].

OBJECTIVE: To detect the expression of L-type amino acid transporter 1 (LAT1) in non-Hodgkin's lymphoma (NHL) tissues, and analyze its effect on clinicopathological characteristics and prognosis of patients. METHODS: A total of 92 NHL patients who were treated in our hospital from January 2017 to April 2019 were collected. The expression of LAT1 in NHL tissue was detected by immunohistochemistry and compared between patients with different pathological features (including sex, Ann Arbor stage, extranodal infiltration, Ki-67). The risk factors affecting mortality were analyzed using univariate and multivariate Cox proportional hazards regression. Receiver operating characteristic (ROC) curve was used to detect the predictive value of percentage of LAT1-positive cells in NHL tissue for patient mortality, and analyzing the effect of percentage of LAT1-positive cells on survival rate. RESULTS: LAT1 was positively expressed in NHL tissue. The high expression rate of LAT1 in Ann Arbor stage III and IV groups were higher than that in Ann Arbor stage I group, that in extranodal infiltration group was higher than non-extranodal infiltration group, and that in Ki-67 positive expression group was higher than Ki-67 negative expression group (all P < 0.05). The remission rate after 3 courses of treatment in high-LAT1 expression group was 70.7%, which was lower than 91.2% in low-LAT1 expression group (P < 0.05). Ann Arbor stage III and IV, extranodal invasion, Ki-67 positive expression and increased expression of LAT1 (LAT1-positive cell percentage score ≥2) were risk factors for mortality. The cut-off value of percentage of LAT1-positive cells for predicting NHL death was 45.6%, and the area under the ROC curve was 0.905 (95%CI: 0.897-0.924). The 3-year survival rate of high-LAT1 level group (the percentage of LAT1-positive cells≥45.6%) was 50.00%, which was lower than 78.26% of low-LAT1 level group (P < 0.05). CONCLUSION: The expression level of LAT1 in NHL tissue increases, which affects Ann Arbor stage and extranodal infiltration of patients. LAT1 is a risk factor for death.

Update on FDG-PET in pediatric lymphoma.

Lymphoma represent the third most common malignant disease in childhood and adolescence. They are divided into pediatric Hodgkin lymphoma (P-HL) and pediatric non-Hodgkin lymphoma (P-NHL). In P-HL, excellent cure rates are achieved through combined modality treatment using chemotherapy and radiotherapy. For more than 20 years, FDG-PET has been an integral part of the treatment and guides its intensity through improved staging and precise assessment of chemotherapy response. In P-NHL, good cure rates are achieved with chemotherapy alone. At present FDG-PET plays only a subordinate role in the treatment setting. Its potential to contribute to treatment management is far from being fully utilised. In this article, the current status of FDG-PET in pediatric lymphoma is presented in detail. The core elements are the sections on staging and response assessment. In addition, challenges and pitfalls are discussed and future developments are outlined.

Effects of Cannabidiol, ∆9-Tetrahydrocannabinol, and WIN 55-212-22 on the Viability of Canine and Human Non-Hodgkin Lymphoma Cell Lines.

In our previous study, we demonstrated the impact of overexpression of CB1 and CB2 cannabinoid receptors and the inhibitory effect of endocannabinoids (2-arachidonoylglycerol (2-AG) and Anandamide (AEA)) on canine (Canis lupus familiaris) and human (Homo sapiens) non-Hodgkin lymphoma (NHL) cell lines' viability compared to cells treated with a vehicle. The purpose of this study was to demonstrate the anti-cancer effects of the phytocannabinoids, cannabidiol (CBD) and ∆9-tetrahydrocannabinol (THC), and the synthetic cannabinoid WIN 55-212-22 (WIN) in canine and human lymphoma cell lines and to compare their inhibitory effect to that of endocannabinoids. We used malignant canine B-cell lymphoma (BCL) (1771 and CLB-L1) and T-cell lymphoma (TCL) (CL-1) cell lines, and human BCL cell line (RAMOS). Our cell viability assay results demonstrated, compared to the controls, a biphasic effect (concentration range from 0.5 µM to 50 µM) with a significant reduction in cancer viability for both phytocannabinoids and the synthetic cannabinoid. However, the decrease in cell viability in the TCL CL-1 line was limited to CBD. The results of the biochemical analysis using the 1771 BCL cell line revealed a significant increase in markers of oxidative stress, inflammation, and apoptosis, and a decrease in markers of mitochondrial function in cells treated with the exogenous cannabinoids compared to the control. Based on the IC50 values, CBD was the most potent phytocannabinoid in reducing lymphoma cell viability in 1771, Ramos, and CL-1. Previously, we demonstrated the endocannabinoid AEA to be more potent than 2-AG. Our study suggests that future studies should use CBD and AEA for further cannabinoid testing as they might reduce tumor burden in malignant NHL of canines and humans.

Lenalidomide, rituximab (R2), and ixazomib for frontline treatment of high risk follicular and indolent non-Hodgkin lymphoma.

Lenalidomide and rituximab (R2) is an effective frontline treatment for patients with indolent B-cell non-Hodgkin lymphoma (iNHL). We investigated the safety and efficacy of addition of the proteasome inhibitor ixazomib to R2 for treatment of iNHL through a phase I/II clinical trial for high-risk patients. Twenty patients were enrolled, 18 were treated. The target dose of ixazomib 4 mg weekly was achieved during dose escalation. The most common treatment-related adverse events (AEs) were low grade gastrointestinal, rash, neuropathy, and myalgia/arthralgia. There were 33% grade 2 and 17% grade 3 infections. With median follow-up of 5.2 years, four patients discontinued treatment due to lymphoma progression. Best overall response rate (ORR) was 61.2% [55.6% CR, 5.6% PR): 22.2% had stable disease and 16.7% had disease progression. Kaplan-Meier estimates of progression free and overall survival (OS) were 73% and 87% at 36 months, respectively. R2 can safely be combined with ixazomib for treatment-naïve iNHL patients.

B-Lymphoblastic Lymphoma in Children: A Case Series From a Single Institution.

BACKGROUND: Pediatric B-lymphoblastic lymphoma is an uncommon subtype of non-Hodgkin lymphoma. Studies regarding the biology, clinical course, and approach to relapse are limited. OBSERVATIONS: We present a series of children with B-lymphoblastic lymphoma to describe the clinical course at diagnosis and relapse as well as the role of tumor cytogenetics, immunotherapy, and hematopoietic stem cell transplant. CONCLUSIONS: The prognostic significance of cytogenetic changes in B-lymphoblastic lymphoma is not well described but may offer improved risk stratification. Immunotherapy may offer salvage options for relapsed disease and can serve as a bridge to transplant.

Tertiary care center experience: An overview of primary mediastinal lymphomas.

BACKGROUND: Mediastinal lymphoma is uncommon, and only 10% of lymphomas occur primarily in the mediastinum. Very few Indian studies have discussed the frequency, presentation, and diagnostic approach of primary mediastinal lymphomas. AIMS: This study aims to detail the frequency and histological features of mediastinal lymphomas diagnosed in our Institute, discuss the close differentials, and compare the morphological and immunohistochemistry (IHC) features of primary mediastinal lymphomas. SETTINGS AND DESIGN: A retrospective observational study. MATERIALS AND METHODS: Fifty-nine cases of primary mediastinal lymphomas diagnosed over 5 years using hematoxylin and eosin (H and E)-stained and IHC slides. STATISTICAL ANALYSIS USED: Descriptive statistics. RESULTS AND CONCLUSIONS: Forty-five (76%) cases had predominant involvement of the anterior mediastinum; Hodgkin lymphoma, and non-Hodgkin lymphoma constituted 12 and 47 cases, respectively. T lymphoblastic lymphoma comprises the most common primary mediastinal lymphoma. There is a marked difference between the demographic profiles of cases with primary mediastinal lymphomas in India and worldwide. A meticulous histological examination to direct a limited panel of IHC markers can help arrive at the final diagnosis in settings where molecular and cytogenetic studies are not performed.

Epidemiologic and Clinical Patterns of Malignant Lymphoma in Qatar 2013-2017: A Population-Based Cohort Study.

INTRODUCTION: Lymphoma, encompassing common non-Hodgkin lymphoma (NHL) and less common Hodgkin lymphoma (HL), represents significant hematological malignancies. Advancements in treatment modalities have reshaped survival rates, particularly in NHL. This complexity results in varying outcomes, some requiring extended observation periods and multiple chemotherapy treatments. The primary objective was to explore and compare the overall survival (OS) of HL and NHL at 1, 3, and 5-year follow-ups among adult lymphoma patients in Qatar during January 2013-December 2017. Further objectives encompass comparing the most prevalent histological types, clinical and epidemiological traits of HL and NHL, as well as secondary aims of assessing clinical features, treatment, response, disease-free survival, and OS. METHODS: A retrospective, descriptive study of consecutive cases was conducted at Qatar's NCCCR between 2013 and 2017. Inclusion criteria involved patients ≥18 years old, of any gender and clinical stage at diagnosis, who received chemotherapy and had known outcomes. Descriptive statistics were applied, and survival analysis utilized Kaplan-Meier curves. STATA version 13.0 facilitated data analysis. RESULTS: Between 2013 and 2017, 414 individuals in Qatar were diagnosed with lymphoma. The median age at diagnosis was 49 years (IQR 36-95 years; p < 0.001) across all patients. Males exhibited a higher likelihood of developing HL and NHL, comprising 74% and 70% of cases, respectively, though this difference was statistically insignificant (p = 0.45). Among NHL-B subtypes, mature B-cell neoplasms (60%) predominated, while lymphocyte-rich subtype (49%) was prominent in HL cases. With a median follow-up of 17.3 months, OS rates at 1, 3, and 5 years were 99%, 82%, and 64%, respectively for all lymphoma patients. Subtype stratification revealed trends in 3-year follow-up OS (94 vs. 82%) for HL and NHL, with 5-year OS of 67% and 60%, respectively. HL demonstrated higher OS throughout the study period compared to NHL (p < 0.001), though median OS remained unreached. CONCLUSIONS: Diffuse large B-cell lymphoma emerged as the most prevalent subtype among lymphomas in Qatar. Generally, HL exhibited superior survival rates, at 67% compared to 60% for NHL. Minor deflation in survival rates, particularly for HL, might be attributed to Qatar's immigration patterns.

Zanubrutinib plus Cytarabine in Patients with Refractory/Relapsed Primary Central Nervous System Lymphoma.

INTRODUCTION: Primary central nervous system lymphoma (PCNSL) is a rare subtype of aggressive extranodal non-Hodgkin lymphoma. Currently, there is no standard of care for the treatment of refractory or relapsed PCNSL (r/r PCNSL). We conducted a prospective single-arm phase II study to evaluate zanubrutinib plus cytarabine for r/r PCNSL. METHODS: Using Simon's two-stage design, we analyzed 34 patients who received high-dose cytarabine (3.0 g/m2 once daily) for 2 days and zanubrutinib (160 mg twice daily) for 21 days each cycle for up to 6 cycles. The study was registered at www.chictr.org.cn as #ChiCTR2000039229. RESULTS: The median follow-up was 19 months. The overall response rate was 64.7% (95% confidence interval [CI], 47.9-78.5%) with a complete remission or unconfirmed complete remission rate of 47.1% (16/34) and a partial remission rate of 17.6% (6/34). The median progression-free survival was 4.5 months (95% CI, 1.5-9.4), and the median OS was 18 months (95% CI, 9.5 to not estimable). The median duration of the response was 9 months (95% CI, 3.2 to not estimable). The most common treatment-emergent adverse events were thrombocytopenia (55.9%). No treatment-related death occurred. CONCLUSION: Zanubrutinib and cytarabine showed efficacy in r/r PCNSL with an acceptable safety profile.

Clinical pharmacology strategies to accelerate the development of polatuzumab vedotin and summary of key findings.

The favorable benefit-risk profile of polatuzumab vedotin, as demonstrated in a pivotal Phase Ib/II randomized study (GO29365; NCT02257567), coupled with the need for effective therapies in relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL), prompted the need to accelerate polatuzumab vedotin development. An integrated, fit-for-purpose clinical pharmacology package was designed to support regulatory approval. To address key clinical pharmacology questions without dedicated clinical pharmacology studies, we leveraged non-clinical and clinical data for polatuzumab vedotin, published clinical data for brentuximab vedotin, a similar antibody-drug conjugate, and physiologically based pharmacokinetic and population pharmacokinetic modeling approaches. We review strategies and model-informed outcomes that contributed to regulatory approval of polatuzumab vedotin plus bendamustine and rituximab in R/R DLBCL. These strategies made polatuzumab vedotin available to patients earlier than previously possible; depending on the strength of available data and the regulatory/competitive environment, they may also prove useful in accelerating the development of other agents.