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Biomarkers for immune checkpoint inhibitors (ICIs) response and resistance include PD‐L1 expression and other environmental factors, among which the gut microbiome (GM) is gaining increasing interest especially in lymphomas. To explore the potential role of GM in this clinical issue, feces of 30 relapsed/refractory lymphoma (Hodgkin and primary mediastinal B‐cell lymphoma) patients undergoing ICIs were collected from start to end of treatment (EoT). GM was profiled through Illumina, that is, 16S rRNA sequencing, and subsequently processed through a bioinformatics pipeline. The overall response rate to ICIs was 30.5%, with no association between patients clinical characteristics and response/survival outcomes. Regarding GM, responder patients showed a peculiar significant enrichment of Lachnospira, while non‐responder ones showed higher presence of Enterobacteriaceae (at baseline and maintained till EoT). Recognizing patient‐related factors that may influence response to ICIs is becoming critical to optimize the treatment pathway of heavily pretreated, young patients with a potentially long‐life expectancy. These preliminary results indicate potential early GM signatures of ICIs response in lymphoma, which could pave the way for future research to improve patients prognosis with new adjuvant strategies. [ABSTRACT FROM AUTHOR]

The International Conference on Malignant Lymphoma (ICML) is a prominent global event where experts in lymphoma research gather to share new findings and advancements in the field. The 17th ICML meeting focused on various topics, including the role of superenhancers and enhancer RNAs in different types of lymphomas, epigenetic mechanisms in B- and T-cell lymphomas, and the impact of epigenetic alterations and the tumor microenvironment in follicular helper T-cell lymphoma. The conference also explored the effectiveness of epigenetic agents in modulating the tumor microenvironment and response to CAR T-cell therapy. Other areas of discussion included genetic subtypes of diffuse large B-cell lymphoma, the use of human brain organoids to study central nervous system lymphomas, and the cellular origin of Hodgkin Reed Sternberg cells in Hodgkin lymphoma. The conference highlighted the importance of understanding the biology of lymphomas to improve treatment strategies. [Extracted from the article]

Lymphomas are a heterogeneous group of diseases that originate from T, B or natural killer cells. Lymphoma treatment is based on chemotherapy, radiotherapy, and monoclonal antibody (mAb) or other immunotherapies. The P‐selectin glycoprotein ligand 1 (PSGL‐1) is expressed at the surface of hematological malignant cells and has been shown to have a pro‐oncogenic role in multiple myeloma and lymphoma. Here, we investigated the expression and therapeutic potential of PSGL‐1 in T and B cell lymphomas. By flow cytometry analysis, we found that PSGL‐1 was expressed in both T and B cell‐derived lymphoma cell lines but generally at higher levels in T cell lymphoma cell lines. For most T and B cell‐derived lymphoma cell lines, in vitro targeting with the PL1 mAb, which recognizes the PSGL‐1 N‐terminal extracellular region and blocks functional interactions with selectins, resulted in reduced cell viability. The PL1 mAb pro‐apoptotic activity was shown to be dose‐dependent, to be linked to increased ERK kinase phosphorylation, and to be dependent on the MAP kinase signaling pathway. Importantly, anti‐PSGL‐1 treatment of mice xenografted with the HUT‐78 cutaneous T‐cell lymphoma cell line resulted in decreased tumor growth, had no effect on in vivo proliferation, but increased the levels of apoptosis in tumors. Anti‐PSGL‐1 treatment of mice xenografted with a Burkitt lymphoma cell line that was resistant to anti‐PSGL‐1 treatment in vitro, had no impact on tumorigenesis. These findings show that PSGL‐1 antibody targeting triggers lymphoma cell apoptosis and substantiates PSGL‐1 as a potential target for lymphoma therapy. [ABSTRACT FROM AUTHOR]

Primary cutaneous B‐cell lymphomas (PCBCLs) are lymphoproliferative disorders that appear on the skin without evidence of extracutaneous manifestations at the time of diagnosis. There is a lack of evidence‐based guidelines for their clinical management due to the availability of very few large scale studies and controlled clinical trials. Here we present and discuss a series of major unmet clinical needs (UCNs) in the management of PCBCLs by a panel of 16 experts involved in research and clinical practice of PCBCL. The Panel produced recommendations on the appropriateness of the clinical decisions concerning the identified clinical needs and proposed research for improving the knowledge needed to solve them. Recommendations and proposals were achieved by multiple‐step formalized procedures to reach a consensus after a comprehensive analysis of the scientific literature. Recommendations and proposals lay in the domain of classification uncertainties of PCBCL, optimization of diagnosis, optimization of prognosis, optimization of staging and critical issues on therapeutic strategies with particular focus on new treatments. These recommendations are intended for use not only by experts but above all by dermatologists and hematologists with limited experience in the field of PCBCLs as well as general practitioners. [ABSTRACT FROM AUTHOR]

The reliability and safety of front‐line ultrasonography guided core needle biopsy (UG‐CNB) performed with specific uniform approach have never been evaluated in a large series of patients with lymphadenopathies suspected of lymphoma. The aim of this study was to assess the overall accuracy of UG‐CNB in the lymph node histological diagnosis, using a standard reference based on pathologist consensus, molecular biology, and/or surgery. We retrospectively checked the findings concerning the application of lymph node UG‐CNB from four Italian clinical units that routinely utilized 16‐gauge diameter modified Menghini needle under power‐Doppler ultrasonographic guidance. A data schedule was sent to all centers to investigate the information regarding techniques, results, and complications of lymph node UG‐CNB in untreated patients over a 12‐year period. Overall, 1000 (superficial target, n = 750; deep‐seated target, n = 250) biopsies have been evaluated in 1000 patients; other 48 biopsies (4.5%), screened in the same period, were excluded because inadequate for a confident histological diagnosis. Most patients were suffering from lymphomas (aggressive B‐cell non‐Hodgkin lymphoma [aBc‐NHL], 309 cases; indolent B‐cell [iBc]‐NHL, 279 cases; Hodgkin lymphoma [HL], 212 cases; and nodal peripheral T‐cell [NPTC]‐NHL, 30 cases) and 100 cases from metastatic carcinoma; 70 patients had non‐malignant disorders. The majority of CNB results met at least one criterion of the composite reference standard. The overall accuracy of the micro‐histological sampling was 97% (95% confidence interval: 95%–98%) for the series. The sensitivity of UG‐CNB for the detection of aBc‐NHL was 100%, for iBc‐NHL 95%, for HL 93%, and for NPTC‐NHL 90%, with an overall false negative rate of 3.3%. The complication rate was low (6% for all complications); no patient suffered from biopsy‐related complications of grade >2 according to the Common Terminology Criteria for Adverse Events. Lymph node UG‐CNB as mini‐invasive diagnostic procedure is effective with minimal risk for the patient. [ABSTRACT FROM AUTHOR]

Diffuse large B‐cell lymphoma (DLBCL) shows a high degree of clinical and biological heterogeneity. Primary testicular lymphoma (PTL) is an extranodal variant of DLBCL associated with a higher risk of recurrence, including contralateral testicles and central nervous system sanctuary sites. Several molecular aberrations, including somatic mutation of MYD88, CD79B, and upregulation of NF‐kB, PDL‐1, and PDL‐2, are thought to contribute to the pathogenesis and poor prognosis of PTL. However, additional biomarkers are needed that may improve the prognosis and help understand the PTL biology and lead to new therapeutic targets. RNA from diagnostic tissue biopsies of the PTL‐ABC subtype and matched nodal DLBCL‐ABC subtype patients was evaluated by mRNA and miRNA expression. Screening of 730 essential oncogenic genes was performed, and their epigenetic connections were examined using the nCounter PAN‐cancer pathway, and Human miRNA assays with the nCounter System (NanoString Technologies). PTL and nodal DLBCL patients were comparable in age, gender, and putative cell of origin (p > 0.05). Wilms tumor 1 (WT1) expression in PTL exceeded that in nodal DLBCL (>6‐fold; p = 0.01, FDR <0.01) and WT1 associated pathway genes THBS4, PTPN5, PLA2G2A, and IFNA17 were upregulated in PTL (>2.0‐fold, p < 0.01, FDR <0.01). Additionally, miRNAs targeting WT1 (hsa15a‐5p, hsa‐miR‐16‐5p, has‐miR‐361‐5p, has‐miR‐27b‐3p, has‐miR‐199a‐5p, has‐miR‐199b‐5p, has‐miR‐132‐3p, and hsa‐miR‐128‐3p) showed higher expression in PTL compared to nodal DLBCL (≥2.0‐fold; FDR 0.01). Lower expression of BMP7, LAMB3, GAS1, MMP7, and LAMC2 (>2.0‐fold, p < 0.01) was observed in PTL compared to nodal DLBCL. This research revealed higher WT1 expression in PTL relative to nodal DLBCL, suggesting that a specific miRNA subset may target WT1 expression and impact the PI3k/Akt pathway in PTL. Further investigation is needed to explore WT1's biological role in PTL and its potential as a therapeutic target. [ABSTRACT FROM AUTHOR]

Zanubrutinib has been approved for the treatment of patients with different lymphoproliferative disorders, and now represents a major breakthrough in the treatment of patients resistant or relapsing after the recommended therapies. Because few systematic studies or comparative randomized clinical trials have been conducted, optimal use of the drug in approved indications is challenging, and questions are emerging on its use in earlier stages of the disorders. This article presents the results of group discussion among an ad hoc constituted panel of experts aimed at identifying and addressing unmet clinical needs (UCNs) in the use of zanubrutinib in the lymphomas which have received the approval of use, specifically Waldenström macroglubulinemia, marginal zone lymphoma and mantle cell lymphoma. Key UCNs were selected according to the criterion of clinical relevance using the Delphi process. The panel produced recommendations and proposals for new studies for the management of the identified UCNs. These recommendations are intended for use not only by expert centers but above all by not experienced hematologists as well as general practitioners. [ABSTRACT FROM AUTHOR]

With improvement in survival after chronic lymphocytic leukemia (CLL) diagnosis, the real‐world burden of second hematological malignancies (SHM) has not been comprehensively assessed in recent era. We analyzed risk, incidence, and outcomes of SHM in CLL patients between 2000 and 2019 using SEER database. CLL patients had greater risk for hematological malignancies than general population [SIR, standardized incidence ratio (95% CI):2.58 (2.46–2.70); p < 0.05]. The risk for subsequent lymphoma increased by 1.75 folds in 2015–2019 compared to 2000–2004. The duration, after CLL diagnosis, of maximum risk for SHM decreased as 60–119 months for time‐period 2000–2004, 6–11 months for 2005–2009 to 2–5 months for 2010–2014 and 2015–2019. Incidence of SHM was 2.5% in CLL survivors (1736/70,346) with lymphoid SHM being more common than myeloid SHM, and DLBCL being the most common pathology (n = 610, 35% of all SHM). Male sex, age ≤65 years at CLL diagnosis, and chemotherapy treatment were associated with higher risk for SHM. The median gap between CLL and SHM diagnoses was 46 months. The median survival for de‐novo‐AML, t‐MN, CML, and aggressive NHL was 63, 86, 95, and 96 months respectively. Although SHM remains rare, there is increased risk in recent era, likely due to improved survival in CLL patients, necessitating active surveillance strategies. [ABSTRACT FROM AUTHOR]

Non‐follicular low‐grade B‐cell lymphomas (LGBCL) are biologically diverse entities that share clinical and histologic features that make definitive pathologic categorization challenging. While most patients with LGBCL have an indolent course, some experience aggressive disease, highlighting additional heterogeneity across these subtypes. To investigate the potential for shared biology across subtypes, we performed RNA sequencing and applied machine learning approaches that identified five clusters of patients that grouped independently of subtype. One cluster was characterized by inferior outcome, upregulation of cell cycle genes, and increased tumor immune cell content. Integration of whole exome sequencing identified novel LGBCL mutations and enrichment of TNFAIP3 and BCL2 alterations in the poor survival cluster. Building on this, we further refined a transcriptomic signature associated with early clinical failure in two independent cohorts. Taken together, this study identifies unique clusters of LGBCL defined by novel gene expression signatures and immune profiles associated with outcome across diagnostic subtypes. [ABSTRACT FROM AUTHOR]

Diffuse large B-cell lymphoma with MYC gene rearrangements: current perspective on treatment of diffuse large B-cell lymphoma with MYC gene rearrangements; case series and review of the literature. Treatment intensification might not improve survival in high-grade B-cell lymphoma with a concurrent MYC and BCL2 and/or BCL6 rearrangement: A retrospective, multicenter, pooled analysis Keywords: double-hit; induction treatment; lymphoma; overall survival; triple-hit EN double-hit induction treatment lymphoma overall survival triple-hit 776 780 5 10/10/23 20231001 NES 231001 PEER REVIEW The peer review history for this article is available at https://www.webofscience.com/api/gateway/wos/peer-review/10.1002/hon.3130. (B) Progression-free survival according to induction treatment. gl In summary, we described a cohort of 259 newly diagnosed HGBCL-DH/TH patients, thereby representing one of the largest retrospective analyses in this high-risk patients' population. [Extracted from the article]

Prognostic nutritional index (PNI), comprised of serum albumin level and lymphocyte count, is associated with the prognosis of several malignant diseases, while the prognostic value of PNI in extranodal natural killer/T cell lymphoma, nasal type (ENKTL) remains unclear. This retrospective multicenter study aimed to investigate the value of PNI in predicting the prognosis of newly diagnosed ENKTL patients by using propensity score matched analysis (PSM). A total of 1022 newly diagnosed ENKTL patients were retrieved from Huaihai Lymphoma Working Group and clinicopathological variables were collected. MaxStat analysis was used to calculate the optimal cut‐off points of PNI and other continuous variables. The median age at diagnosis was 47 years and 69.4% were males, with the 5‐year OS of 71.7%. According to the MaxStat analysis, 41 was the optimal cut‐off point for PNI. The Pseudo R2 before matching was 0.250, and it decreased to less than 0.019 after matching. Confounding factors of the two groups were well balanced after PSM. Multivariable analysis revealed that PNI, Korean Prognostic Index (KPI), eastern cooperative oncology group performance status (ECOG PS), the prognostic index of natural killer lymphoma (PINK) and hemoglobin were independent prognostic factors for ENKTL. The results of subgroup analysis demonstrated that patients with low PNI could predict worse prognosis and re‐stratify patients in ECOG PS ≥ 2, EBER‐positive, the International Prognostic Index (IPI) (HIR + HR), and PINK (HR) groups. PNI combined with IPI, PINK and KPI could improve the prediction efficiency. In conclusion, PNI could accurately stratify the prognosis of ENKTL by PSM analysis and patients with low PNI had poorer prognosis. [ABSTRACT FROM AUTHOR]

Although chemotherapy (CHT) exposure is an established cause of telomere attrition, determinants of telomere length (TL) dynamics after chemotherapy are poorly defined. In this study, we analyzed granulocyte telomere dynamics in 34 adult lymphoma patients undergoing first‐line CHT. TL was measured by southern blot at each CHT cycle and after 1 year from CHT completion. Median age was 59 yrs (range 22–77). Median number of CHT cycles was 6 (range 3–6). The majority of patients (79%, n = 27) experienced TL shortening following CHT exposure. Mean telomere loss was 673 base pairs (bp) by cycle 6. Telomere shortening was an early event as 87% of the total telomere loss (mean 586 bp) occurred by the end of cycle 3, with no significant recovery after 1 year. A significant correlation was observed between baseline TL and total or fractional telomere loss (p < 0.001), with telomere shortening by cycle 3 observed predominantly in male patients with long telomeres at pre‐treatment evaluation. Stratifying the analysis by gender and age only young women (<51 years of age) did not show significant telomere shortening following chemotherapy exposure. These findings indicate that gender and baseline TL are major determinants of TL dynamics following chemotherapy exposure in lymphoma patients. [ABSTRACT FROM AUTHOR]

Patients with recurrent adult T‐cell leukemia/lymphoma (ATL) after allogeneic hematopoietic cell transplantation (allo‐HCT) have a dismal prognosis. We retrospectively evaluated the safety and efficacy of lenalidomide (LEN) in 11 consecutive patients with recurrent ATL after allo‐HCT. The median time from allo‐HCT to ATL recurrence was 111 days (range, 20–1476), and that from allo‐HCT to the initiation of LEN was 162 days (range, 43–1560). The median initial daily dose of LEN was 10 mg (range, 5–25), and the median duration of LEN treatment was 37 days (range, 3–1078). Three patients (27%) achieved complete response and two (18%) achieved partial response (PR). The rates of complete or PR according to the involved site were 57% for skin and 50% for nodal or extranodal lesions. With a median follow‐up of 1033 days (range, 601–1465) among survivors, the 1‐year probability of overall survival (OS) after ATL recurrence was 55%. Grade ≥3 toxicities included cytopenia (n = 4), superficial vein thrombosis (n = 1), and deep vein thrombosis (n = 1). Graft‐versus‐host disease (GVHD) newly developed in five patients (45%) and worsened in four patients (36%). The median duration from the initiation of LEN to GVHD onset or worsening was 5 days (range, 1–9). GVHD was manageable in all patients. Seven patients received mogamulizumab (MOG) for recurrent ATL before LEN treatment. The overall response rates to LEN were 57% in patients who had previously received MOG and 25% in those who had not. The 1‐year probabilities of OS after recurrent ATL were 71% in patients who had previously received MOG and 25% in those who had not. Although cytopenia and GVHD are common among patients with recurrent ATL after allo‐HCT, LEN may improve survival. Administering MOG before LEN may augment treatment efficacy in the allo‐HCT population. [ABSTRACT FROM AUTHOR]

COVID19 in patients affected by lymphoma represents an important challenge because of the higher mortality rate. Anti‐SARS‐CoV‐2 monoclonal antibodies (anti‐S MoAbs) appear promising in this setting. We report a monocentric retrospective study including 176 patients affected by lymphoma which developed SARS‐CoV‐2 infection since the start of COVID19 pandemic. Overall, mortality was 13.1%, with a decreasing trend between first waves to the last wave of pandemic (18.5% vs. 9.4%, p 0.076). Patients receiving anti‐S MoAbs (41.3%) showed inferior mortality rate (overall survival, OS 93.2% vs. 82.7%, p 0.025) with no serious toxicity, reduced documented pneumonia (26% vs. 33%, p 0.005), and reduced need of oxygen support (14.5% vs. 35.7%, p 0.003). Among patients who received 3 doses of vaccine, the employment of anti‐COVID MoAbs showed a trend of superior survival versus those who did not receive Anti‐S MoAbs (OS rates 97.3% vs. 84.2%, p 0.064). On multivariate analysis, active haematological disease (OS 72% (HR 2.49 CI 1.00–6.41), bendamustine exposure (OS 60% HR 4.2 CI 1.69–10.45) and at least one comorbidity (HR 6.53 CI 1.88–22.60) were independent prognostic factors for death. Our study confirms the adverse prognostic role of COVID‐19 in lymphoma patients in presence of active disease, comorbidities and previous exposure to bendamustine. In our experience, anti‐S MoAbs represented a therapeutic option in vaccinated patients. [ABSTRACT FROM AUTHOR]

Extranodal natural killer (NK)/T‐cell lymphoma (ENKTL) is strongly associated with Epstein–Barr virus (EBV) and has a high prevalence in Asian and in Central and South America. About 85% of ENKTLs derive from NK cells and 15% from T‐cells. Various factors have been implicated in the development of ENKTL. Molecular pathogenesis of NK/T‐cell lymphomas include mutations of genes, involving in the Janus Kinase/signal transducer and activator of transcription pathway, RNA helicase family, epigenetic regulation, and tumor suppression. The relationship between ENKTL and human leukocyte antigen has been demonstrated. Radiotherapy plays a key role in the first‐line treatment of early‐stage. In stage III/IV diseases, non‐anthracycline‐regimens‐containing L‐asparaginase are recommended. Although clinical remission after L‐asparaginase‐based combination therapy has been achieved in the majority of patients with advanced‐stage or relapsed/refractory extranodal NK/T‐cell lymphoma‐nasal type, the long‐term overall survival is still poor. Recently, immunotherapy and new therapeutic targets have gained much attention. In this article, we discuss the pathogenesis, diagnosis, prognostic models and management options of ENKTL. [ABSTRACT FROM AUTHOR]

Secondary central nervous system (SCNS) involvement is an infrequent but universally fatal event in diffused large B‐cell lymphoma. The occurrence rate of SCNS involvement is approximately 5% but comes with a poor prognosis ever after. However, existing risk models to predict the incidence and prognosis of these patients with SCNS involvement lack both efficiency and accuracy. Controversy has also been reported regarding which risk factor may best identify the population with a high CNS relapse rate. In this study, we retrospectively analyzed 831 patients with diffused large B‐cell lymphoma, diagnosed between March 2008 and June 2018 in Tianjin Medical University Cancer Institute and Hospital, Beijing Cancer Hospital, and Cancer Hospital of The University of Chinese Academy of Science. Risk factors and nomogram were identified and established based on Fine and Gray's competing risk analysis. Among these patients, 55 (6.6%) of them eventually developed SCNS involvement. The 1‐ and 2‐year incidence for SCNS involvement were 3.9% and 4.7%, respectively. The median time from de novo diagnosis to CNS relapse was 8 months, and the median overall survival of these patients was 28 months. Considering the competing mortality before SCNS involvement, Fine and Gray's competing risk model was performed to analyze the characteristics related to SCNS involvement, and identified risk factors as the multiple extranodal involvements, elevated LDH and AMC level, and the involvement of breast, adrenal gland/kidney, pulmonary and bone. Corresponding factors were integrated into the competing nomogram for SCNS involvement (c‐index = 0.778). In conclusion, we present the first predictive nomogram to evaluate the risk to develop SCNS involvement in de novo DLBCL patients, which may help in both prognostic evaluation and clinical decision for this subgroup. [ABSTRACT FROM AUTHOR]

Natural killer/T cell lymphoma (NKTCL) is a highly aggressive hematological malignancy. However, there is currently no consensus on therapies for refractory/relapsed patients. In this study, we investigated the synergistic anticancer effect and potential mechanism of combining chidamide, a histone deacetylases (HDACs) inhibitor, and etoposide, a DNA‐damaging agent, in NKTCL. We demonstrated that chidamide or etoposide alone dose‐ and time‐dependently inhibited the cell viability of NKTCL cell lines, YT, NKYS and KHYG‐1. Functional experiments suggested that combined chidamide and etoposide treatment exerted synergistic antiproliferation effect and enhanced cell apoptotic death in vitro and in vivo. Furthermore, the expression of DNA damage related proteins was detected and we also examined the alternations in histone acetylation, cell cycle progression, and mitochondrial membrane potential (MMP). The results suggested that increased histone acetylation, cell cycle arrest at the G2/M phase and loss of MMP, converging to greater DNA damage, might account for the synergism of the combination of chidamide and etoposide in NKTCL. Taken together, our study provides an evident for possible application on combining HDACs inhibitors and DNA‐damaging agents for the treatment of NKTCL. [ABSTRACT FROM AUTHOR]

Extranodal natural killer (NK)/T‐cell lymphoma (NKTL) is a rare non‐Hodgkin lymphoma that rarely arise exclusively in or metastasizes to the central nervous system (CNS). Globally, CNS involvement of NKTL heralds a serious prognosis and there is no standard treatment. 19 of 414 patients (4.59%) with ENKL followed were diagnosed with CNS involvement between 2006 and 2020. Two patients had primary CNS (PCNS) NKTL, and 17 patients had secondary CNS (SCNS) invasion. A total of 9 patients survived and 10 patients died. The median overall survival time was 55 months, and the median survival time after CNS invasion was 17 months. The 5‐year cumulative survival probability was 45.7%. In conclusion, CNS risk evaluation and prophylaxis treatment can be carried out for patients with NK/T‐cell lymphoma prognostic index risk group III/IV. In terms of treatment, systemic therapy based on methotrexate combined with radiotherapy and intrathecal chemotherapy can be selected. [ABSTRACT FROM AUTHOR]

Central nervous system (CNS) involvement is rare in primary mediastinal large B‐cell lymphoma (PMLBCL). We aimed to evaluate the incidence of CNS relapse as first treatment failure event and the effect of the induction chemotherapy regimen, central nervous system ‐ international prognostic index (CNS‐IPI) and other clinical and laboratory variables on the risk of CNS relapse in 564 PMLBCL patients treated with immunochemotherapy. Only 17 patients (3.0%) received CNS prophylaxis. During a 55‐month median follow‐up only 8 patients experienced CNS relapse as first event, always isolated. The 2‐year cumulative incidence of CNS relapse (CI‐CNSR) was 1.47% and remained unchanged thereafter. The CI‐CNSR was not affected by the chemotherapy regimen (R‐CHOP or R‐da‐EPOCH). None of the established International Prognostic Index factors for aggressive lymphomas predicted CNS relapse in PMLBCL. The 2‐year CI‐CNSR in patients with versus without kidney involvement was 13.3% versus 0.96% (p < 0.001); 14.3% versus 1.13% with versus without adrenal involvement (p < 0.001); and 10.2% versus 0.97% with versus without either kidney or adrenal involvement. CNS‐IPI was also predictive (2‐year CI‐CNSR in high‐risk vs. intermediate/low‐risk: 10.37% vs. 0.84%, p < 0.001). However, this association may be driven mainly by kidney and/or adrenal involvement. In conclusion, in PMLBCL, CNS relapse is rare and appears to be strongly associated with kidney and/or adrenal involvement. [ABSTRACT FROM AUTHOR]

Patients with relapsed or refractory lymphoma have limited treatment options, requiring newer regimens. In this Phase 1/2 study (NCT03769181), we assessed the safety, efficacy, and pharmacokinetics of isatuximab (Isa, anti‐CD38 antibody) in combination with cemiplimab (Cemi, anti‐programmed death‐1 [PD‐1] receptor antibody; Isa + Cemi) in patients with classic Hodgkin lymphoma (cHL), diffuse large B‐cell lymphoma (DLBCL), and peripheral T‐cell lymphoma (PTCL). In Phase 1, we characterized the safety and tolerability of Isa + Cemi with planned dose de‐escalation to determine the recommended Phase 2 dose (RP2D). Six patients in each cohort were treated with a starting dose of Isa + Cemi to determine the RP2D. In Phase 2, the primary endpoints were complete response in Cohort A1 (cHL anti‐PD‐1/programmed death‐ligand 1 [PD‐L1] naïve), and objective response rate in Cohorts A2 (cHL anti‐PD‐1/PD‐L1 progressors), B (DLBCL), and C (PTCL). An interim analysis was performed when the first 18 (Cohort A1), 12 (Cohort A2), 17 (Cohort B), and 11 (Cohort C) patients in Phase 2 had been treated and followed up for 24 weeks. Isa + Cemi demonstrated a manageable safety profile with no new safety signals. No dose‐limiting toxicities were observed at the starting dose; thus, the starting dose of each drug was confirmed as the RP2D. Based on the Lugano 2014 criteria, 55.6% (Cohort A1), 33.3% (Cohort A2), 5.9% (Cohort B), and 9.1% (Cohort C) of patients achieved a complete or partial response. Pharmacokinetic analyses suggested no effect of Cemi on Isa exposure. Modest clinical efficacy was observed in patients with cHL regardless of prior anti‐PD‐1/PD‐L1 exposure. In DLBCL or PTCL cohorts, interim efficacy analysis results did not meet prespecified criteria to continue enrollment in Phase 2 Stage 2. Isa + Cemi did not have a synergistic effect in these patient populations. [ABSTRACT FROM AUTHOR]

The management of newly diagnosed primary central nervous system lymphoma (PCNSL) includes administration of high‐dose methotrexate based regimens followed by consolidation therapy to minimize the risk of relapse. However, the best consolidation strategy (autologous hematopoietic cell transplant [auto‐HCT] vs. whole‐brain radiotherapy [WBRT]) is controversial. Hence, we performed a systematic review and meta‐analysis of all randomized controlled trials that compared auto‐HCT versus WBRT consolidation for patients with PCNSL after first‐line treatment.The primary outcome was overall survival (OS), while the secondary outcomes included progression‐free survival (PFS), response rates (overall response rate [ORR] and complete remission [CR]), relapse rate, treatment‐related mortality (TRM), and neuropsychological adverse events. We performed a pooled analysis of the single‐arm studies that incorporated auto‐HCT or WBRT consolidation and evaluated neurocognitive outcomes. Only two studies met the inclusion criteria (n = 240). There was no significant difference in OS (HR = 1.50; 95% CI = 0.95–2.36), PFS (HR = 0.99; 95% CI = 0.44–2.22), ORR (RR = 1.48; 95% CI = 0.90–2.44), CR rate (RR = 1.21; 95% CI = 0.90–1.63), relapse rate (RR = 0.46; 95% CI = 0.05–4.28), and TRM (RR = 5.67; 95% CI = 1.01–31.91). The neuropsychological tests to assess neurocognitive domains were different and inconsistently reported in the two studies and therefore we were unable to perform a meta‐analysis but provide a descriptive assessment. Both the studies showed a significant decline in the attention/executive function (based on the trail making test A and trail making test B) in those receiving WBRT compared to auto‐HCT. We found 9 single‐arm phase II studies that reported data on outcomes associated with either auto‐HCT (5 studies) or WBRT (4 studies) consolidation. Of these, two studies (n = 43) reported data on neurocognitive decline following auto‐HCT consolidation. Pooled proportion of patients with neurocognitive decline in these studies was 6% (95% CI, 0%–17%) for those receiving auto‐HCT and there was no heterogeneity between studies (I2 = 0%). Three studies (n = 122) reported data on neurocognitive decline following WBRT consolidation. Pooled proportion of patients with neurocognitive decline in these studies was 43% (95% CI, 11%–78%) for those receiving WBRT and there was high heterogeneity between studies (I2 = 94%). There was significant heterogeneity between subgroups (p = 0.035). The outcomes were not significantly different in patients with PCNSL receiving auto‐HCT or WBRT consolidation therapies, however, there is a higher degree of neurocognitive decline associated with WBRT compared to auto‐HCT consolidation. The decision to choose a consolidation strategy needs to be individualized based on age, frailty, and co‐morbidities. [ABSTRACT FROM AUTHOR]

A prospective multicentre experience of early administration of anti‐SARS‐CoV‐2 spike protein neutralizing monoclonal antibodies (MA) with efficacy among patients with hematological malignancies and early‐stage COVID‐ 19 was reported by Weinbergerová et al. The study validated the safety and efficacy of MA early use among hematological patients with newly diagnosed early‐stage COVID‐19 in terms of alleviating infection course and decreasing mortality. However no reference to new variant (Delta and Omicron) or other MA (e.g., Sotrovimab) has been reported. We reported our monocentric experience of 8 aggressive lymphoma patients with Omicron infection, 7 of whom treated with this MA in our Institution between December 2021 and February 2022. Among the patients treated with Sotrovimab nobody experienced neither SARS‐CoV2 reactivation, nor other infectious events. One patients on active lymphoma treatment was hospitalized for pneumonia and treated with remdesivir. In 4/8 patients negativization of molecular swab occurred concomitantly to symptoms resolution with a median of 5.25 days, while the other 4 patients remained persistently positive with a median of 26.3 days. In this group, in order to maintain the chemo/chemoimmunotherapy (CT/CIT) dose‐density, lymphoma treatment was reassumed independently on molecular swab analysis. SARS‐CoV‐2 negativization occurred with a median of 7.7 days after the resumption of CT/CIT. The one patient treated with remdesivir, although still positive to molecular swab, restarted R‐COMP regimen at symptoms resolution too, but experienced an Omicron pneumonia exacerbation. This is the first case series reported in literature of patients affected by Omicron variant in which Sotrovimab seems to provide a resolution of COVID‐19 disease, even in patient with molecular swab positive persistence too. Patients with aggressive lymphoma histologies should not be deprived of the best available treatment of their disease after sotrovimab administration, even in the presence of a still positive Omicron swab. [ABSTRACT FROM AUTHOR]

The Ukrainian Lymphoma Registry (ULR) was established in 2019 with the aim of monitoring the quality of diagnosis, staging, and treatment of lymphoma in Ukraine. Between September 2019 and October 2021, 546 patients with newly diagnosed lymphoma were prospectively registered. All cases were diagnosed according to the 2016 updated WHO lymphoma classification. The male‐to‐female ratio (M/F) for the whole population was 0.7, with a median age of 46 years (range 18–95). The adoption of the 2016 WHO classification resulted in the identification of 36 different lymphoma subtypes, with 132 cases (24.2%) classified differently compared to the 2008 WHO classification. Only 12 cases (2.8%) were true new entities, including seven cases of high‐grade B‐cell lymphoma NOS, three of anaplastic large B‐cell lymphoma, ALK‐negative, 1 case of HHV8+ DLBCL NOS, and 1 of high‐grade B‐cell lymphoma with C‐MYC and BCL2/BCL6 rearrangement. Moreover, 55 (61.1%) entities, including 37 defined by WHO 2008 and 18 defined by WHO 2016, were not represented at all. The analysis of cases registered in the ULR provides a comprehensive breakdown of the subtypes, stage distribution, and treatment of malignant lymphomas (ML) in Ukraine, supporting the usefulness of prospective data collection and timely reporting. We believe that this study is the first step toward a better understanding of the real‐life outcomes of patients with ML. [ABSTRACT FROM AUTHOR]

Aberrant activity of histone deacetylases (HDACs) is frequently detected in B‐cell lymphomas, which indicated the therapeutic implications of HDAC inhibitors for B‐cell malignancies. We have discovered that lymphoma cells treated with HDAC inhibitor presented with activation of Bruton tyrosine kinase (BTK) which played an important role in the development of B‐cell malignancies. Therefore, our study intended to explore whether the addition of ibrutinib (BTK inhibitor) to chidamide (HDAC inhibitor) could generate combined anti‐tumor effects in B‐cell lymphomas. Using cell viability assay, cell cycle and apoptosis kit, we demonstrated an evident synergistic action of ibrutinib and chidamide in inhibiting tumor cell proliferation and motility. Consistent with in vitro data, the synergistic anti‐tumor effects were also observed in multiple tumor‐bearing mice models. By performing RNA‐seq and flow cytometry of tumor tissue, the enhancement of anti‐tumor immunity was observed with the co‐treatment of chidamide and ibrutinib. Together, these mechanistic insights indicated that simultaneously targeting BTK and HDAC could be a promising clinical therapy for B‐cell lymphomas. [ABSTRACT FROM AUTHOR]

Natural killer (NK)/T cell lymphoma is a highly aggressive subtype of non‐Hodgkin lymphoma. The prognosis of patients with natural killer T cell lymphoma (NKTCL) remains poor. More potent treatment strategies are urgently needed to improve the survival of these patients with R/R NKTCL. CD30 expression has been reported to occur in about 40% of NK/T cell lymphoma. Brentuximab vedotin (BV), a monomethyl auristatin E conjugated CD30 antibody, targets CD30 to kill cancer cells. Therapeutic combination of BV and bendamustine has been shown to be highly effective in Hodgkin lymphoma. We investigated efficacy of BV in treating NKTCL as a single therapy, and in combination with bendamustine in vitro and in vivo. We determined CD30 expression levels in 6 NKTCL cell lines. The efficiency of lymphoma cell inhibition by BV correlates with CD30 expression. We also determined the efficacy of BV in combination with bendamustine and found synergistic effects with bendamustine in NKTCL. Combined BV and bendamustine treatment exerted synergistic antiproliferation effect and enhanced cell apoptotic in vitro and in vivo. Brentuximab vedotin and bendamustine synergistically arrested cell cycle at the G2/M phase in NKTCL cell lines. The combination of BV and bendamustine was demonstrated to synergistically damage DNA in NKTCL. This study provides a reference for possible application on using BV for the treatment of NKTCL, either as a single agent or in combination with bendamustine. [ABSTRACT FROM AUTHOR]

Takezaki et al. analyzed the outcome of 57 patients with indolent lymphomas treated with Bendamustine plus Rituximab (BR) according to the number of cycles received, showing that patients who discontinued BR after four cycles had similar outcomes compared to patients who received five or six cycles. Considering the similarities but also the differences between indolent lymphomas and chronic lymphocytic leukemia (CLL), we enriched the results obtained with a cohort of CLL patients treated with BR starting from the experience of the Lazio region group on CLL. Out of 115 patients, 97 (84%) received 4–6 cycles of BR, while 18 (16%) received 1–3 cycles. The outcome of the group of patients who received at least 4 cycles was superior in terms of response rate (ORR 96% vs. ORR 83%, p = 0.041; CR 58% vs. CR 28%, p = 0.052 respectively) and PFS [median PFS 52.6 (40.3–64.9) versus 26.2 (19.3–33.0) months, p < 0.001]. The number of patients undergoing 4 cycles of BR (4‐cycles group) and 5–6 cycles (over‐4‐cycles group) was 9 and 88, respectively. Compared to analysis conducted by the Japanese group in indolent lymphomas, in CLL we did not observe any difference between the outcome of the 4‐cycles group and the over‐4‐cycles group in terms of ORR (89% vs. 97%, p = 0.268) and in survival [median PFS 40.8 (13.7–67.8) versus 52.6 (38.7–66.5) months, p = 0.117]. Moreover, we observed that patients who achieved a clinical CR showed overlapping outcomes with patients who received more than 4 cycles [CR vs. non‐CR median PFS not reached vs. 11.0 months; over‐4‐cycles group median PFS 52.6 months (40.3–64.9); p < 0.001]. Nowadays chemoimmunotherapy with BR is reserved to fit elderly CLL patients, and there are many chemo‐free treatment options available; therefore, discontinuation after 4 cycles may be permissible in patients who obtained a CR in order to limit toxicity as much as possible. [ABSTRACT FROM AUTHOR]

B Introduction: b Outcomes are poor for patients with relapsed/refractory ( I R i / I R i ) large B-cell lymphoma (LBCL). SUBCUTANEOUS EPCORITAMAB INDUCES DEEP, DURABLE COMPLETE REMISSIONS IN RELAPSED/REFRACTORY LARGE B-CELL LYMPHOMA: LONGER FOLLOW-UP FROM THE PIVOTAL EPCORE NHL-1 TRIAL. [Extracted from the article]

A PHASE I STUDY OF SPLIT-COURSE BRIDGING RADIOTHERAPY (SC-BRT) PRIOR TO COMMERCIAL CD19 CAR T-CELL THERAPIES FOR PATIENTS WITH RELAPSED OR REFRACTORY B-CELL LYMPHOMAS B Introduction: b Despite remarkable responses after chimeric antigen receptor T-cells (CART), most relapse within 6 mos and only 35%-50% achieve sustained remission. B Methods: b This is a Phase I trial in which adult B-cell lymphoma patients planned for commercial anti-CD19 CART undergo bridging RT (BRT). [Extracted from the article]

B Methods: b The Phase 3 trial design will enroll 300 adult patients with high-risk, histologically confirmed LBCL based on the 2016 WHO classification, including diffuse large B-cell lymphoma, HGBL, and transformed follicular or marginal zone lymphoma (Swerdlow SH, et al. I Blood i . 2016). B Introduction: b The nearly 40% of patients with large B-cell lymphoma (LBCL) who are refractory to or relapse after current first-line standard-of-care (SOC) regimens, such as R-CHOP (rituximab [R] + cyclophosphamide [C], doxorubicin [H], vincristine [O], and prednisone [P]) and DA-EPOCH-R (dose-adjusted etoposide [DA-E]), have poor prognoses. ZUMA-23: A GLOBAL, PHASE 3, RANDOMIZED CONTROLLED STUDY OF AXICABTAGENE CILOLEUCEL VERSUS STANDARD OF CARE AS FIRST-LINE THERAPY IN PATIENTS WITH HIGH-RISK LARGE B-CELL LYMPHOMA. [Extracted from the article]

B Introduction: b Glofitamab is a CD20xCD3 bispecific antibody delivered in a fixed course of 12 three-weekly cycles. GLOFITAMAB MONOTHERAPY IN PATIENTS WITH RELAPSED/REFRACTORY (R/R) LARGE B-CELL LYMPHOMA (LBCL): EXTENDED FOLLOW-UP AND LANDMARK ANALYSES FROM A PIVOTAL PHASE II STUDY. [Extracted from the article]

Survival analysis is shown in the figure f. A total of 11/70 patients received second-line chemotherapy, and only 1 patient survived to receive treatment. The prognosis of patients with a large tumor focus, serous cavity effusion and delayed chemotherapy during treatment is poor. CART treatment can significantly prolong the survival rate and total survival period of r/r patients, but it cannot improve the prognosis of r/r patients with I ARID1A i . [Extracted from the article]

Among them, 11 patients with R/R DLBCL achieved objective responses rate(ORR) of 63.6% and the disease control rate (DCR) was 72.7% (4 complete remissions [CR], and 3 partial remissions [PR]), and 1 stable disease [SD]). Notably, one patient with double-expression DLBCL who was refractory to two lines of therapy, including chidamide combined with R-CHOP and R-ICE regimen, obtained PR in cycle 3 and CR in cycle 5. B Introduction: b Purinostat Mesylate (PM) is a uniquely potent and selective HDAC I/IIb inhibitor. [Extracted from the article]

B Conclusions: b Through CRISPR/Cas9 genome-wide knockout screening and long-time low-dose asparaginase treatment and then sequencing comparing with parental cell lines, we found that SOS1 gene can significantly affect asparaginase sensitivity in NKTCL. B Introduction: b Extranodal nature killer/T cell lymphoma (NKTCL) accounts for about 6% of all kinds of lymphoma. [Extracted from the article]

B Introduction: b Although in a phase III trial of extranodal MZL (EMZL) patients (pts) the combination of rituximab and chlorambucil had superior progression-free and event-free survival (PFS, EFS) compared to either drug given alone (Zucca et al. JCO 2016), there is no standard front-line therapy for MZL pts requiring systemic treatment, and no randomized trial specifically addressed initial treatment for the splenic (SMZL) and nodal (NMZL) MZL subtypes. [Extracted from the article]

FOURTH GENERATION HUCART19-IL18 PRODUCES DURABLE RESPONSES IN LYMPHOMA PATIENTS PREVIOUSLY RELAPSED/REFRACTORY TO ANTI-CD19 CAR T-CELL THERAPY B Introduction: b Lymphoma (NHL) patients (pts) relapsing/refractory (R/R) to anti-CD19 chimeric antigen receptor T-cells (CART) represent a challenging group in need of effective therapies. B Conclusions: b HuCART19-IL18 therapy results in durable responses in pts with CD19+ NHL who are R/R to prior 2 SP nd sp generation anti-CD19 CART. [Extracted from the article]

CC-99282 plus R-CHOP in patients (pts) with previously untreated aggressive B-cell lymphoma (a-BCL): early safety and efficacy results from a phase 1b study CC-220-DLBCL-001 (NCT04884035) is an open-label, multicenter, dose-escalation and expansion trial to assess safety and preliminary efficacy of CC-99282 or CC-220 plus R-CHOP for untreated a-BCL. B Introduction: b Up to 30-40% of pts with diffuse large BCL relapse/become refractory after first-line chemo-immunotherapy with R-CHOP. [Extracted from the article]

B Conclusions: b With approximately 9 mo of follow-up, pembro 400 mg Q6W had robust antitumor activity in pts with R/R cHL and R/R PMBCL, with ORR similar to that with pembro 200 mg Q3W. B Introduction: b Pembrolizumab (pembro) was originally approved by the FDA for the treatment of R/R cHL and R/R PMBCL at 200 mg every 3 weeks (Q3W). Treatment-related AEs occurred in 24 pts (40%) with R/R cHL and 2 (33.3%) with R/R PMBCL; grade >=3 treatment-related AEs occurred in 3 pts (5%) and 1 pt (16.7%), respectively. [Extracted from the article]

Transfusion needs may impact patients' quality of life and CAR T-cells efficacy through transfusion-related immunomodulation. Transfusion needs after CD19 CAR T-cells for large B-cell lymphoma: predictive factors and impact on outcome. B Introduction: b Patients undergoing CAR T-cell therapy may experience severe cytopenias due to lymphodepleting chemotherapy and/or CAR T-cells. [Extracted from the article]

Although the advent of non-anthracycline-based and L-asparaginase containing chemotherapy has contributed to enhancing the prognosis of ENKL patients, recent clinical results of ENKL patients have not been well assessed. The proportion of patients who underwent subsequent hematopoietic stem cell transplantation (HSCT) was also significantly higher in patients treated with SMILE than the other regimens (65% vs. 18%, I P i < 0.001). B Background: b Extranodal NK/T-cell lymphoma (ENKL) is a particular subtype of lymphoma that is characterized by the expression of multi-drug resistance-associated P-glycoprotein. [Extracted from the article]

B Conclusion: b With a 51% OS-rate at 12 months CART seem to be a very effective therapeutic option in heavily pre-treated r/r PCNSL or SCNSL, particularly for pts being refractory to prior therapy. Pts with involvement of the CNS were excluded from most CART trials; however, anecdotal reports suggest that CART might be an effective treatment option for such pts. B Introduction: b The prognosis of patients (pts) with diffuse large B-cell lymphoma (DLBCL) and involvement of the central nervous system (CNS) remains dismal. [Extracted from the article]

B Introduction: b Several new therapeutic agents have been introduced in recent years for the treatment of relapsed/refractory (r/r) aggressive B cell lymphoma (ABCL) (diffuse large B cell lymphoma [DLBCL] and high-grade B cell lymphomas [HGBCL]), such as new monoclonal antibodies (MA), bispecific antibodies (BA) and CAR-T cell therapy. From 354 patients that received >2 lines of treatment, 130 (37%) received CAR-T cell therapy, 69 (19%) pola-based, 5 (1%) TL, 55 (15%) BA, and 299 (84 %) did not receive NTs. Novel therapies for the treatment of relapsed-refractory aggressive B-cell lymphoma increase survival. [Extracted from the article]

Pts presenting with synchronous systemic/CNS LBCL can have durable remission and survival when treated with frontline systemic and CNS-directed chemoimmunotherapy. The most common CNS site was brain parenchyma (60%), followed by leptomeninges (58%), intraocular (7%), and spinal cord (2%); 23% of pts had >1 CNS site at diagnosis. B Introduction: b Large B-cell lymphoma with synchronous systemic and central nervous system (CNS) involvement at diagnosis is a rare entity with a poor prognosis. [Extracted from the article]

All adult patients were eligible, provided they had a clinical picture coherent with that of the PMBCL, were registered in the local databases from 1/1/2007 to 31/12/2019 with a histological diagnosis of PMBCL, and were treated with an RCHT. B Introduction: b PMBCL is an uncommon neoplasia showing unique clinicopathologic and demographic features. [Extracted from the article]

B Introduction: b There are several suitable consolidation strategies for primary central nervous system lymphoma (PCNSL) after induction therapy including whole brain radiotherapy [<=24 Gy reduced-dose, RD-WBRT or >24 Gy standard-dose, SD-WBRT], non-myeloablative chemotherapy (e.g., cytarabine, cyt) or autologous hematopoietic cell transplant (AHCT). Longitudinal consolidation patterns were analyzed by Fisher exact test. Consolidation strategies and outcomes were stratified by decade and MSKCC recursive partitioning analysis (RPA) class 1 (age <50), 2 (age >=50, KPS >= 70) or 3 (age >=50, KPS < 70). [Extracted from the article]

LISOCABTAGENE MARALEUCEL (LISO-CEL) IN R/R CHRONIC LYMPHOCYTIC LEUKEMIA (CLL)/SMALL LYMPHOCYTIC LYMPHOMA (SLL): PRIMARY ANALYSIS OF TRANSCEND CLL 004 B Introduction: b Achieving durable CR with current treatment is uncommon in patients (pts) with R/R CLL/SLL that progressed on BTKi and failed venetoclax (ven)-based treatment. Keyword: cellular therapies B Conflicts of interests pertinent to the abstract b B T. Siddiqi b Consultant or advisory role: Astra Zeneca, BMS, Celgene, Kite pharma, Beigene, Abbvie Research funding: Astra Zeneca, BMS, Celgene, Oncternal, Ascentage pharma, Kite pharma, TG therapeutics, Pharmacyclics, Juno therapeutics Other remuneration: Speaker's Bureau: Astra Zeneca, BMS, Beigene B D. G. Maloney b Consultant or advisory role: A2 Biotherapeutics, Member of the Scientific Advisory Board GRAPH Navan Technologies, Member of the Scientific Advisory Board GRAPH Chimeric Therapeutics, Member of the Scientific Advisory Board GRAPH Genentech, Member and Chair of the Lymphoma Steering Committee GRAPH BMS, Member of the JCAR017 EAP-001 Safety Review Committee GRAPH BMS, Member, CLL Strategic Council GRAPH ImmPACT Bio, Member, Clinical Advisory Board, CD19/CD20 bi-specific CAR-T Cell Therapy Program GRAPH Gilead Sciences, Member, Scientific Review Committee, Research Scholars Program in Hematologic Malignancies GRAPH Interius. [Extracted from the article]

In patients who responded to epcoritamab, ctDNA levels decreased rapidly, with the majority of patients achieving CR having a deep ctDNA response by C3D1. B Results: b ctDNA quantification was concordant between the assays when within the dynamic range of the clonoSEQ assay (>80% in paired samples tested); however, a greater sensitivity of the AVENIO assay was observed, allowing further exploratory analyses of ctDNA using this platform. B Introduction: b The emergence of novel, more potent therapeutics in the treatment of patients with large B-cell lymphoma (LBCL) has resulted in higher rates of responses and highlighted a need for additional methods, such as minimal residual disease (MRD), to determine the depth and quality of response and potentially guide duration of treatment. [Extracted from the article]

B Introduction: b T-cell immunostimulatory antibodies invoke potent anti-tumour responses in murine models but their ability to induce T-cell immunostimulation in the immunosuppressive tumour microenvironment (TME) of patients, or induce clinical responses, is lacking. Determinants of response to T-cell stimulation by CD27 antibody therapy in lymphoma: The RiVa trial Agonistic CD27 antibody stimulation of T cells enhanced tumour killing by anti-CD20 in murine models led to the RiVa trial (NCT3307746): a phase IIa study of rituximab (ritux) and varlilumab (varli, anti-CD27) in relapsed/refractory B-cell lymphoma. [Extracted from the article]

The IELSG37 (NCT01599559) randomized trial was planned with a non-inferiority design to test whether RT can be omitted in PMBCL patients who achieve a complete metabolic response (CMR) after immunochemotherapy. Mediastinal radiotherapy (RT) may consolidate responses to dose-intensive immunochemotherapy; however, it increases the risk of second malignancies and coronary or valvular heart disease. B Introduction: b Primary mediastinal B-cell lymphoma (PMBCL) has a poor prognosis if remission is not rapidly achieved, or the disease recurs. [Extracted from the article]

Pts with >=20% reduction after ibrutinib received TEDDi-R; those with <20% reduction received TEDD-R. Therapy was 4 cycles × 21d with IT therapy (no maintenance) and mostly outpatient. The 1-year PFS and OS for pts with CD10 neg tumors was 48.0% and 64.7% B Conclusions: b Ibrutinib-responsive SCNSL achieves high rates of CR to TEDDi-R that can be durable. Ibrutinib-responsive tumors are mostly CD10 negative and TEDDi-R may improve the outcomes of this subgroup. [Extracted from the article]