Loncastuximab tesirine in Chinese patients with relapsed or refractory diffuse large B-cell lymphoma: a multicenter, open-label, single-arm, phase II trial.

Patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) have a poor prognosis. Loncastuximab tesirine (Lonca), an antibody conjugate targeting CD19, has demonstrated significant clinical benefit in R/R DLBCL in a global phase 2 LOTIS-2 study. In the China bridging pivotal phase 2 OL-ADCT-402-001 study, eligible patients aged ≥18 years with R/R DLBCL who had failed ≥ 2 lines of systemic therapies were enrolled and treated with Lonca every 3 week with 150 µg/kg for 2 cycles; then 75 µg/kg for subsequent cycles (up to 1 year). The primary endpoint was overall response rate (ORR) assessed by independent review committee. Primary analyses for efficacy and safety were performed on the patients who received at least one treatment and had at least 6 months of follow-up following an initial documented response. As of data-cutoff, 64 patients received Lonca (median: 4.0 cycles [range: 1 to 17]). The median number of prior lines of therapies was 3.0 (range: 2 to 12). The ORR was 51.6% (95% CI: 38.7% to 64.2%), and the complete response rate was 23.4%. Hematological events accounted for the majority of the most common (≥15%) Grade ≥3 treatment-emergent adverse events (TEAEs), in which increased gamma glutamyltransferase (25.0%), and hypokalaemia (18.8%) also were reported. Serious TEAEs were reported in 35 of 64 patients with 4 fatal TEAEs. In conclusion, Lonca monotherapy demonstrated clinically meaningful efficacy and was well-tolerated in heavily pretreated Chinese patients with R/R DLBCL, which was consistent with the results of the LOTIS-2 study in Caucasian patients.

Time to lymphoma treatment within 24 months in 'watch and wait' follicular lymphoma is associated with inferior outcomes: A multicentre analysis.

Some 'watch and wait' (W&W) FL patients suffer from rapid progression in a short term. Herein, we sought to identify these patients and also develop a risk score to screen them at diagnosis. Between 2008 and 2022, a total of 411 FL patients managed by the W&W strategy from 16 cancer centres were retrospectively enrolled in this study, and their time to lymphoma treatment (TLT) and progression-free survival (PFS) were evaluated. Thirty-five percent of W&W FL patients experienced TLT within 24 months (TLT24) after diagnosis. Their 5-year PFS rate was significantly lower than those without treatment at 24 months (62.3% vs. 89.5%). In multivariable analysis, five factors were identified as independent predictors of TLT24: stages III-IV, ß2 microglobulin ≥3 mg/L, lymphocyte-to-monocyte ratio <3.8, bone marrow involvement and spleen enlargement (above umbilical line). Their AUCs for TLT24 were 0.76 (95% CI, 0.70-0.82) in the training cohort and 0.76 (95% CI, 0.67-0.85) in the validation cohort respectively. Risk groups were also associated with PFS (p < 0.001). In FL patients initially managed by W&W, TLT24 was associated with poor outcomes. This multivariable model helps screening for predicting TLT24, which may be useful to identify candidates for early interventional treatment.

Flavonoids as therapeutic agents for epilepsy: unveiling anti-inflammatory and antioxidant pathways for novel treatments.

Epilepsy, a chronic neurological disorder affecting millions globally, is often exacerbated by neuroinflammation and oxidative stress. Existing antiepileptic drugs primarily manage symptoms, leaving the disease's progression largely unaddressed. Flavonoids, ubiquitous plant metabolites with potent anti-inflammatory and antioxidant properties, show promise in epilepsy treatment. Unlike conventional therapies, they target multiple pathophysiological processes simultaneously, offering a comprehensive approach to this complex neurological disorder. This review explores the dual role of flavonoids in mitigating neuroinflammation and reducing oxidative stress through various molecular pathways. By inhibiting key inflammatory mediators and pathways such as NF-κB, MAPK, JNK, and JAK, flavonoids offer neuronal protection. They enhance the body's natural antioxidant defenses by modulating enzyme activities, including superoxide dismutase, catalase, and glutathione peroxidase. Moreover, flavonoids influence crucial antioxidant response pathways like PI3K/AKT, Nrf2, JNK, and PKA. Despite their therapeutic promise, the low bioavailability of flavonoids poses a considerable challenge. However, cutting-edge strategies, including nanotechnology and chemical modifications, are underway to improve their bioavailability and therapeutic efficacy. These advancements support the potential of flavonoids as a valuable addition to epilepsy treatment strategies.

Insights into uveitis from Brentuximab vedotin in refractory Hodgkin's lymphoma: a case report and brief review.

This case report describes a 16-year-old patient with refractory Hodgkin's lymphoma who developed bilateral anterior and intermediate uveitis as an adverse reaction to Brentuximab vedotin (BV). This is a rare case of an ocular adverse reaction potentially related to BV, with symptoms like blurred vision, decreased visual acuity, photophobia, and redness. Potential mechanisms include BV targeting CD30+ T cells in the uveal tissue or an immune response triggered by the microtubule-disrupting agent MMAE within BV. This highlights the need for vigilant monitoring of ocular adverse events in BV-treated patients and further research into their mechanisms and management.

Benefit of consolidative radiation in patients with extranodal limited-stage diffuse large B-cell lymphoma: a multicenter retrospective study in China.

Approximately 40% of limited-stage (stage I and II) diffuse large B-cell lymphoma (LS-DLBCL) presents with extranodal disease. Extranodal LS-DLBCL may have significant biological differences and associated with worse outcomes than nodal disease. Although rituximab based chemoimmunotherapy is standard of first-line treatment, the role of consolidative radiotherapy (RT) in this particular subgroup is controversial. In this multicenter retrospective study, we evaluated the survival benefit of consolidative RT in patients diagnosed with extranodal LS-DLBCL and received rituximab-based chemoimmunotherapy with or without consolidative RT. A total of 328 patients were included, 129 patients (39.3%) received chemoimmunotherapy and consolidative RT, and 199 patients (60.7%) received chemoimmunotherapy alone. With a median follow-up of 5.1 years (range, 0.3-14.8 years), 5-year progression-free survival (PFS) and overall survival (OS) for all patients were 75.4% and 83.9%, respectively. In multivariate analyses, the addition of consolidative RT was associated with superior OS (P = 0.004) and PFS (P = 0.005). High stage-modified International Prognosis Index (SM-IPI) risk predicted worse OS (P = 0.001) and PFS (P = 0.005). Also, propensity score-matched analyses showed RT improved both OS (hazard ratio [HR] 0.228, 95% confidence index [CI] 0.111-0.467, P < 0.001) and PFS (HR 0.308, 95% CI 0.167-0.566, P < 0.001). Among patients who achieved CR, 49 patients (16.6%) developed disease relapse, of which 30.6% relapsed at local sites. Consolidative RT significantly reduced relapse risk (P = 0.002). Our results demonstrated that consolidative RT significantly improved outcomes in patients with extranodal LS-DLBCL in the rituximab era.

Potential Mechanism of Tibetan Medicine Liuwei Muxiang Pills against Colorectal Cancer: Network Pharmacology and Bioinformatics Analyses.

This study aimed to explore the mechanism through which Tibetan medicine Liuwei Muxiang (LWMX) pills acts against colorectal cancer (CRC). We firstly retrieved the active ingredients and the correlated targets of LWMX pills from public databases. The CRC-related targets were determined through bioinformatic analysis of a public CRC dataset. By computing the intersection of the drug-specific and disease-related targets, LWMX pill-CRC interaction networks were constructed using the protein-protein interaction (PPI) method and functional enrichment analysis. Subsequently, we determined the hub genes using machine learning tools and further verified their critical roles in CRC treatment via immune infiltration analysis and molecular docking studies. We identified 81 active ingredients in LWMX pills with 614 correlated targets, 1877 differentially expressed genes, and 9534 coexpression module genes related to CRC. A total of 5 target hub genes were identified among the 108 intersecting genes using machine learning algorithms. The immune infiltration analysis results suggested that LWMX pills could affect the CRC immune infiltration microenvironment by regulating the expression of the target hub genes. Finally, the molecular docking outcomes revealed stable binding affinity between all target hub proteins and the primary active ingredients of LWMX pills. Our findings illustrate the anti-CRC potential and the mechanism of action of LWMX pills and provide novel insights into multitarget medication for CRC treatment.

Treatment advances in high-grade gliomas.

High-grade gliomas (HGG) pose significant challenges in modern tumour therapy due to the distinct biological properties and limitations of the blood-brain barrier. This review discusses recent advancements in HGG treatment, particularly in the context of immunotherapy and cellular therapy. Initially, treatment strategies focus on targeting tumour cells guided by the molecular characteristics of various gliomas, encompassing chemotherapy, radiotherapy and targeted therapy for enhanced precision. Additionally, technological enhancements are augmenting traditional treatment modalities. Furthermore, immunotherapy, emphasising comprehensive tumour management, has gained widespread attention. Immune checkpoint inhibitors, vaccines and CAR-T cells exhibit promising efficacy against recurrent HGG. Moreover, emerging therapies such as tumour treating fields (TTFields) offer additional treatment avenues for patients with HGG. The combination of diverse treatments holds promise for improving the prognosis of HGG, particularly in cases of recurrence.

Diagnosis of bone marrow involvement in angioimmunoblastic T-cell lymphoma should be based on both [18F]FDG-PET/CT and bone marrow biopsy findings.

OBJECTIVE: During the initial staging of certain lymphoma subtypes, 18 F-fluorodeoxyglucose positron emission tomography/computed tomography ([18F]FDG-PET/CT) has become an alternative to bone marrow biopsy (BMB) for detecting bone marrow (BM) involvement. However, whether [18F]FDG-PET/CT can accurately detect BM involvement in angioimmunoblastic T-cell lymphoma (AITL) remains unknown. Our study aimed to assess the diagnostic and prognostic capability of [18F]FDG-PET/CT for detecting BM involvement in AITL. Methods: This retrospective study included 84 individuals newly diagnosed with AITL who underwent baseline BMB and [18F]FDG-PET/CT. "BM involvement" was defined as one or both of the following: 1) angioimmunoblastic T-cells detected in the BM; or 2) initially heightened focal uptake having disappeared on follow-up [18F]FDG-PET/CT. The ability of [18F]FDG-PET/CT to detect BM cancerous lesions was respectively analyzed by BM involvement confirmed by BMB or the aforementioned definition as the reference standard. The patients' clinical characteristics and survival and prognostic outcomes were respectively analyzed. RESULTS: Of the 84 participants, five (6.0%) displayed positive BMB and PET/BM results, 17 (20.2%) had BMB-positive but PET/BM-negative results, eight (9.5%) showed BMB-negative but PET/BM-positive outcomes, and 54 (64.3%) displayed negative BMB and PET/BM outcomes. Using pre-defined BM involvement as the reference standard, [18F]FDG-PET/CT exhibited a specificity of 100%, sensitivity of 40%, negative predictive value (NPV) of 75%, and positive predictive value (PPV) of 100%. In contrast, using BMB-detected BM involvement as reference, [18F]FDG-PET/CT exhibited a sensitivity, specificity, PPV, and NPV of 38.5%, 76.1%, 22.7%, and 87.1%, respectively. Among patients with PET/BM-positive and BMB-negative outcomes, 62.5% (5/8) underwent upstaging from III to IV. In 58.8% (10/17) of patients who were initially diagnosed with stage II/III disease based on the [18F]FDG-PET/CT results, repeat BMB resulted in upstaging to IV. PET/BM-negative patients had a higher 3-year progression-free survival rate (38.3% vs. 22.8%, p = 0.018) and 3-year overall survival rate (64.4% vs. 34.6%, p = 0.011) than PET/BM-positive patients. CONCLUSION: In AITL patients, PET/BM-positive results may obviate the necessity for repeat BMB to ascertain confirm BM involvement. PET/BM-negative results do not definitively exclude BM involvement. The combined use of [18F]FDG-PET/CT and BMB can increase the diagnostic accuracy of BM involvement for AITL patients.

Genetically determined telomere length as a risk factor for hematological malignancies: evidence from Mendelian randomization analysis.

BACKGROUND: Over the past years, the exact correlation between telomere length and hematological malignancies was still not fully understood. METHODS: We performed a two-sample Mendelian randomization study to investigate the causal relationship between telomere length and hematological malignancies. We selected genetic instruments associated with telomere length. The genetic associations for lymphoid and hematopoietic malignant neoplasms were obtained from the most recent publicly accessible FinnGen study R9 data. Inverse variant weighted (IVW) analysis was adopted as the primary method, and we also performed the weighted-median method and the MR-Egger, and MRPRESSO methods as sensitive analysis. RESULTS: Significant associations have been observed between telomere length and primary lymphoid (IVW: OR = 1.52, P = 2.11 × 10-6), Hodgkin lymphoma (IVW: OR = 1.64, P = 0.014), non-Hodgkin lymphoma (IVW: OR = 1.70, P = 0.002), B-cell lymphoma (IVW: OR = 1.57, P = 0.015), non-follicular lymphoma (IVW: OR = 1.58, P = 1.7 × 10-3), mantle cell lymphoma (IVW: OR = 3.13, P = 0.003), lymphoid leukemia (IVW: OR = 2.56, P = 5.92E-09), acute lymphocytic leukemia (IVW: OR = 2.65, P = 0.021) and chronic lymphocytic leukemia (IVW: OR = 2.80, P = 8.21 × 10-6), along with multiple myeloma (IVW: OR = 1.85, P = 0.016). CONCLUSION: This MR study found a significant association between telomere length and a wide range of hematopoietic malignancies. But no substantial impact of lymphoma and hematopoietic malignancies on telomere length has been detected.

Genomic features reveal potential benefit of adding anti-PD-1 immunotherapy to treat non-upper aerodigestive tract natural killer/T-cell lymphoma.

Natural killer/T-cell lymphoma (NKTCL) is a highly heterogeneous disease with a poor prognosis. However, the genomic characteristics and proper treatment strategies for non-upper aerodigestive tract NKTCL (NUAT-NKTCL), a rare subtype of NKTCL, remain largely unexplored. In this study, 1589 patients newly diagnosed with NKTCL at 14 hospitals were assessed, 196 (12.3%) of whom had NUAT-NKTCL with adverse clinical characteristics and an inferior prognosis. By using whole-genome sequencing (WGS) and whole-exome sequencing (WES) data, we found strikingly different mutation profiles between upper aerodigestive tract (UAT)- and NUAT-NKTCL patients, with the latter group exhibiting significantly higher genomic instability. In the NUAT-NKTCL cohort, 128 patients received frontline P-GEMOX chemotherapy, 37 of whom also received anti-PD-1 immunotherapy. The application of anti-PD-1 significantly improved progression-free survival (3-year PFS rate 53.9% versus 17.0%, P = 0.009) and overall survival (3-year OS rate 63.7% versus 29.2%, P = 0.01) in the matched NUAT-NKTCL cohort. WES revealed frequent mutations involving immune regulation and genomic instability in immunochemotherapy responders. Our study showed distinct clinical characteristics and mutational profiles in NUAT-NKTCL compared with UAT patients and suggested adding anti-PD-1 immunotherapy in front-line treatment of NUAT-NKTCL. Further studies are needed to validate the efficacy and related biomarkers for immunochemotherapy proposed in this study.

Phase I study of the Syk inhibitor sovleplenib in relapsed or refractory mature B-cell tumors.

Sovleplenib (HMPL-523) is a selective spleen tyrosine kinase (Syk) inhibitor with anti-tumor activity in preclinical models of B-cell malignancy. We conducted a dose-escalation and dose-expansion phase I study of sovleplenib in patients with relapsed/ refractory mature B-cell tumors. Dose escalation followed a 3+3 design; patients received oral sovleplenib (200-800 mg once daily [q.d.] or 200 mg twice daily [b.i.d.], 28-day cycles). During dose expansion, patients were enrolled into four cohorts per lymphoma classification and treated at the recommended phase II dose (RP2D) (clinicaltrials gov. Identifier: NCT02857998). Overall, 134 Chinese patients were enrolled (dose escalation, N=27; dose expansion, N=107). Five patients experienced dose-limiting toxicities: one each of amylase increased (200 mg q.d.), febrile neutropenia (800 mg q.d.), renal failure (800 mg q.d.), hyperuricemia and blood creatine phosphokinase increased (200 mg b.i.d.) and blood bilirubin increased and pneumonia (200 mg b.i.d.). RP2D was determined as 600 mg (>65 kg) or 400 mg (≤65 kg) q.d.. The primary efficacy end point of independent review committee-assessed objective response rate in indolent B-cell lymphoma was 50.8% (95% confidence interval: 37.5- 64.1) in 59 evaluable patients at RP2D (follicular lymphoma: 60.5%, marginal zone lymphoma: 28.6%, lymphoplasmacytic lymphoma/Waldenström macroglobulinemia, 0%). The most common (≥10% patients) grade ≥3 treatment-related adverse events in the dose-expansion phase were decreased neutrophil count (29.9%), pneumonia (12.1%) and decreased white blood cell count (11.2%). Pharmacokinetic exposures increased dose-proportionally with ascending dose levels from 200-800 mg, without observed saturation. Sovleplenib showed anti-tumor activity in relapsed/refractory B-cell lymphoma with acceptable safety. Further studies are warranted.

Golidocitinib, a selective JAK1 tyrosine-kinase inhibitor, in patients with refractory or relapsed peripheral T-cell lymphoma (JACKPOT8 Part B): a single-arm, multinational, phase 2 study.

BACKGROUND: Golidocitinib, a selective JAK1 tyrosine-kinase inhibitor, has shown encouraging anti-tumour activity in heavily pre-treated patients with relapsed or refractory peripheral T-cell lymphoma in a phase 1 study (JACKPOT8 Part A). Here, we report the full analysis of a phase 2 study, in which we assessed the anti-tumour activity of golidocitinib in a large multinational cohort of patients. METHODS: We did a single-arm, multinational, phase 2 trial (JACKPOT8 Part B) in 49 centres in Australia, China, South Korea, and the USA. Eligible patients were adults (aged ≥18 years) with relapsed or refractory peripheral T-cell lymphoma who had received at least one previous line of systemic therapy and an Eastern Cooperative Oncology Group performance status of 0-2. Patients were given oral golidocitinib 150 mg once daily until disease progression or other discontinuation criteria were met. The primary endpoint was the CT-based objective response rate, assessed by an independent review committee (IRC) per Lugano 2014 classification. The activity analysis set included all patients who received at least one dose and whose pathological diagnosis of peripheral T-cell lymphoma had been retrospectively confirmed by a central laboratory and who had at least one measurable lesion at baseline assessed by IRC. The safety analysis set included all patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, NCT04105010, and is closed to accrual and follow-up is ongoing. FINDINGS: Between Feb 26, 2021, and Oct 12, 2022, we assessed 161 patients for eligibility, of whom 104 (65%) were enrolled and received at least one dose of study drug; the activity analysis set included 88 (85%) patients (median age 58 years [IQR 51-67], 57 [65%] of 88 were male, 31 [35%] were female, and 83 [94%] were Asian). As of data cutoff (Aug 31, 2023; median follow-up was 13·3 months [IQR 4·9-18·4]), per IRC assessment, the objective response rate was 44·3% (95% CI 33·7-55·3; 39 of 88 patients, p<0·0001), with 21 (24%) patients having a complete response and 18 (20%) having a partial response. In the safety analysis set, 61 (59%) of 104 patients had grade 3-4 drug-related treatment-emergent adverse events. The most common grade 3-4 drug-related treatment-emergent adverse events were neutrophil count decreased (30 [29%]), white blood cell count decreased (27 [26%]), lymphocyte count decreased (22 [21%]), and platelet count decreased (21 [20%]), which were clinically manageable and reversible. 25 (24%) patients had treatment-related serious adverse events. Deaths due to treatment-emergent adverse events occurred in three (3%) patients: two (2%) due to pneumonia (one case with fungal infection [related to golidocitinib] and another one with COVID-19 infection) and one (1%) due to confusional state. INTERPRETATION: In this phase 2 study, golidocitinib showed a favourable benefit-risk profile in treating relapsed or refractory peripheral T-cell lymphoma. The results of this study warrant further randomised clinical studies to confirm activity and assess efficacy in this population. FUNDING: Dizal Pharmaceutical.

Appropriate timing to perform an interim 18F-FDG PET/CT in patients with nasal-type extranodal natural killer/T cell lymphoma.

Interim 18F-FDG PET/CT (I-PET) has a role in response evaluation and treatment guidance in patients with nasal-type extranodal natural killer/T cell lymphoma (ENKTL). However, there was no agreement on the timing of I-PET performed, after chemotherapy or after chemoradiotherapy. We aimed to find the appropriate timing for I-PET by assessing the prognostic value of I-PET in response evaluation in ENKTL patients. Two hundred and twenty-seven ENKTL patients who had undergone I-PET were retrospectively included. All patients were grouped based on their therapeutic strategy received, chemotherapy or chemoradiotherapy. The Deauville 5-point score (DS) was used to interpret the I-PET images. The hazard ratio (HR) and C-index were used to measure the discriminatory and prognostic capacities of I-PET performed at different times. One hundred and six patients underwent the I-PET after chemotherapy (chemotherapy group), while I-PET was performed after chemoradiotherapy in 121 patients (chemoradiotherapy group). Eighty-seven patients were classified as metabolic remission (DS score of 1-3), while the other 140 were classified as non-metabolic remission (DS score of 4-5) according to the Deauville criteria. There were no significant survival differences between patients in metabolic remission and in non-metabolic remission in either progression-free survival (PFS, p = 0.406) or overall survival (OS, p = 0.350). In the chemotherapy group, patients in metabolic remission had significantly superior PFS than patients in non-metabolic remission (p = 0.012). For OS, a discriminative trend was also found on the survival curve between patients in metabolic remission and in non-metabolic remission (p = 0.082). In the chemoradiotherapy group, there was no significant difference in PFS (P = 0.185) or OS (P = 0.627) between patients in metabolic remission and in non-metabolic remission. I-PET after chemotherapy yields higher discriminative power and has the ability for prognostic prediction in nasal-type ENKTL patients. I-PET after radiochemotherapy has no prognostic value. Thus, the appropriate timing for I-PET is after chemotherapy but before radiotherapy for response evaluation in nasal-type ENKTL patients.

Efficacy and safety of anti-CD38 monoclonal antibodies in patients with relapsed/refractory multiple myeloma: a systematic review and meta-analysis with trial sequential analysis of randomized controlled trials.

Objectives: The current study aims to evaluate the safety and efficacy of anti-CD38 monoclonal antibodies (mAbs) among patients with relapsed/refractory multiple myeloma (RRMM) through meta-analysis. Methods: As of June 2023, we searched PubMed, Web of Science, Embase and the Cochrane Library. Randomized controlled trials (RCTs) which compared the clinical outcomes of anti-CD38 mAbs plus immunomodulatory drugs (IMiDs) or proteasome inhibitors (PIs) plus dexamethasone and IMiDs (or PIs) and dexamethasone alone for RRMM patients were included. Efficacy outcomes were mainly evaluated with progression-free survival (PFS) and overall survival (OS). The safety was analyzed with hematologic and nonhematologic treatment-emergent adverse events (TEAEs). All results were pooled using hazard ratio (HR), relative risk (RR), and their 95% confidence interval (CI) and prediction interval (PI). Results: This meta-analysis included 11 RCTs in total. Compared with IMiDs (or PIs) and dexamethasone alone, anti-CD38 mAbs in combination with IMiDs (or PIs) and dexamethasone significantly prolonged PFS (HR: 0.552, 95% CI = 0.461 to 0.659, 95% PI = 0.318 to 0.957) and OS (HR: 0.737, 95% CI = 0.657 to 0.827, 95% PI = 0.626 to 0.868) in patients with RRMM. Additionally, RRMM patients receiving anti-CD38 mAbs in combination with IMiDs (or PIs) and dexamethasone achieved higher rates of overall response (RR: 1.281, 95% CI = 1.144 to 1.434, 95% PI = 0.883 to 1.859), complete response or better (RR: 2.602, 95% CI = 1.977 to 3.424, 95% PI = 1.203 to 5.628), very good partial response (VGPR) or better (RR: 1.886, 95% CI = 1.532 to 2.322, 95% PI = 0.953 to 3.731), and minimum residual disease (MRD)-negative (RR: 4.147, 95% CI = 2.588 to 6.644, 95% PI = 1.056 to 16.283) than those receiving IMiDs (or PIs) and dexamethasone alone. For TEAEs, the rates of hematologic and nonhematologic TEAEs, including thrombocytopenia, neutropenia, upper respiratory tract infection (URTI), pneumonia, bronchitis, dyspnea, diarrhea, pyrexia, back pain, arthralgia, fatigue, insomnia, and hypertension, were higher in the anti-CD38 mAbs in combination with IMiDs (or PIs) and dexamethasone group than in the IMiDs (or PIs) and dexamethasone group. Conclusion: Our study showed that anti-CD38 mAbs in combination with IMiDs (or PIs) and dexamethasone improved PFS and OS, and achieved higher rates of overall response, complete response or better, VGPR or better, and MRD-negative, as well as higher rates of thrombocytopenia, neutropenia, URTI, pneumonia, bronchitis, dyspnea, diarrhea, pyrexia, back pain, arthralgia, fatigue, insomnia, and hypertension in RRMM patients. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023431071.

Primary breast diffuse large B-cell lymphoma in the rituximab era: A retrospective study of the Chinese Southwest Oncology Group.

BACKGROUND: Primary breast diffuse large B-cell lymphoma (PB-DLBCL) is a rare subtype of extranodal DLBCL, and the standard treatment remains controversial. In this study, we aimed to define the optimal treatment management in the rituximab era. METHODS: A total of 5089 newly diagnosed DLBCL patients treated with rituximab-containing immunochemotherapy between 2008 and 2019 from the Chinese Southwest Oncology Group-affiliated institutes were identified, of whom 135 diagnosed with PB-DLBCL were eligible for this analysis. RESULTS: PB-DLBCL accounted for 2.7% of all DLBCLs. With a median follow-up of 4.2 years, the 5-year overall survival and progression-free survival rates were 84.8% and 71.6%, respectively. Breast and central nervous system (CNS) relapses were the main cause of treatment failure. We observed that consolidative breast radiotherapy (RT) significantly decreased breast relapse risk (5-year risk, 2.9% vs. 20.1%, p = 0.007). The CNS relapse risk was lower for patients who received high-dose methotrexate (HD-MTX) than for patients who did not (5-year risk, 0% vs. 15.2%, p = 0.015). We further screened the genetic mutation profile of 20 patients from two institutes, and found that MYD88 (25%) and CD79B mutations (25%) frequently occur in PB-DLBCL. In addition, four patients with MYD88 and/or CD79B mutations experienced CNS relapse, while three patients with MYD88 and/or CD79B mutations who received HD-MTX did not experience CNS relapse. CONCLUSION: Collectively, our results indicate combined modality therapy including rituximab-containing immunochemotherapy and consolidative breast RT is a promising approach for PB-DLBCL, while HD-MTX is useful for preventing CNS relapse.

Prognostic significance of the systemic immune-inflammation index in patients with extranodal natural killer/T-cell lymphoma.

Background: The systemic immune-inflammation index (SII) is based on the neutrophil, platelet, and lymphocyte counts, and has been identified as a prognostic marker in multiple types of cancer. However, the potential value of the SII for predicting survival outcomes in patients with extranodal natural killer/T-cell lymphoma (ENKTCL) has not been investigated thus far. Method: This study included 382 patients with ENKTCL treated with asparaginase-base regimens from 2021 to 2017 in West China Hospital (Chengdu, China). Clinical and demographic variables, as well as the prognostic value of the SII, were analyzed using Cox proportional hazards regression analysis. Results: The complete and objective response rates were 55.8% and 74.9%, respectively. Patients with high SII were associated with a lower rate of complete response, higher rate of B symptoms, and serum lactate dehydrogenase levels above or equal to the upper limits of normal (p < 0.01). Patients with low SII were linked to better overall survival and progression-free survival than those with high SII (p < 0.01). Patients with early-stage disease or prognostic model for natural killer lymphoma with Epstein-Barr virus, defined as the low-risk group, could be further stratified according to the SII (p < 0.01). Negative prognostic factors were determined using the Cox proportional hazards regression analysis, which identified four variables: Eastern Cooperative Oncology Group performance status score ≥2, Stage III/IV disease, positivity for Epstein-Barr virus DNA in plasma, and high SII. Predictive nomograms for the prediction of 3- and 5-year overall survival, as well as progression-free survival, were constructed based on those four variables. The nomograms demonstrated favorable discriminating power. Conclusion: The SII is a novel prognostic marker for ENKTCL, which may be used for the prediction of poorer survival in low-risk patients.

Effect of genetic liability to migraine and its subtypes on breast cancer: a mendelian randomization study.

BACKGROUND: The relationship between migraine and breast cancer risk has generated conflicting findings. We attempted to assess the association between migraine and breast cancer risk using Mendelian randomization (MR) analysis. METHODS: We selected genetic instruments associated with migraine from a recently published genome-wide association studies (GWAS). Inverse variant weighted (IVW) analysis was adopted as the main method, and we also performed the weighted-median method and the MR‒Egger, MR pleiotropy residual sum and outlier (MR-PRESSO), and MR Robust Adjusted Profile Score (MR-RAPS) methods as supplements. RESULTS: Our MR suggested that any migraine (AM) was a risk factor for overall breast cancer (IVW: odds ratio (OR) = 1.072, 95% confidence intervals (CI) = 1.035-1.110, P = 8.78 × 10- 5, false discovery rate (FDR) = 7.36 × 10- 4) and estrogen receptor-positive (ER+) breast cancer (IVW: OR = 1.066, 95% CI = 1.023-1.111, P = 0.0024; FDR = 0.0108) but not estrogen receptor-negative (ER-) breast cancer. In its subtype analysis, women with a history of migraine without aura (MO) had an increased risk of ER- breast cancer (IVW: OR = 1.089, 95% CI = 1.019-1.163, P = 0.0118, FDR = 0.0354), and MO was suggestively associated with the risk of overall breast cancer (FDR > 0.05 and IVW P < 0.05). No significant heterogeneity or horizontal pleiotropy was found in the sensitivity analysis. CONCLUSION: This study suggested that women with AM have an increased risk of overall breast cancer and ER + breast cancer. MO was suggestively associated with the risk of overall breast cancer and ER- breast cancer.

Impact of robotic and open surgery on patient wound complications in gastric cancer surgery: A meta-analysis.

This meta-analysis is intended to evaluate the effect of both robotic and open-cut operations on postoperative complications of stomach carcinoma. From the earliest date until June 2023, a full and systemic search has been carried out on four main databases with keywords extracted from 'Robot', 'Gastr' and 'Opene'. The ROBINS-I instrument has been applied to evaluate the risk of bias in nonrandomized controlled trials. In these 11 trials, a total of 16 095 patients had received surgical treatment for stomach cancer and all 11 trials were nonrandomized, controlled trials. Abdominal abscesses were reported in 5 trials, wound infections in 8 trials, haemorrhage in 7 trials, wound dehiscence in 2 trials and total postoperative complications in 4 trials. Meta-analyses revealed no statistically significantly different rates of postoperative abdominal abscesses among patients who had received robotic operations than in those who had received open surgical procedures (OR, 0.91; 95% CI, 0.25, 3.36; p = 0.89). The incidence of bleeding after surgery was not significantly different from that in both groups (OR, 1.37; 95% CI, 0.69, 2.75; p = 0.37). Similarly, there was no significant difference between the two groups (OR, 0.78; 95% CI, 0.52, 1.18; p = 0.24). No significant difference was found between the two groups (OR, 1. 28; 95% CI, 0.75, 2.21; p = 0.36). No significant difference was found between the two groups of patients who had received the robotic operation and those who had received the surgery after the operation (OR, 1.14; 95% CI, 0.78, 1.66; p = 0.49). Generally speaking, this meta-analysis suggests that the use of robotics does not result in a reduction in certain postsurgical complications, including wound infections and abdominal abscesses. Thus, the use of a microinvasive robot for stomach carcinoma operation might not be better than that performed on the surgical site after the operation. This is a valuable guide for the surgeon to select the operative method.

Efficacy and safety of geptanolimab (GB226) for relapsed/refractory primary mediastinal large B-cell lymphoma: an open-label phase II study (Gxplore-003).

BACKGROUND: This study aimed to assess the efficacy and safety of geptanolimab (GB226), a fully humanized, recombinant anti-programmed cell death-1 monoclonal antibody, in Chinese patients with refractory or relapsed (r/r) primary mediastinal large B-cell lymphoma (PMBCL). METHODS: This was a multicenter, open-label, single-arm phase II study (Gxplore-003), conducted at 43 hospitals in China (NCT03639181). Patients received geptanolimab intravenously at a dose of 3 mg/kg every 2 weeks until documented confirmed disease progression, intolerable toxicity, or any other cessation criteria was met. The primary endpoint was objective response rate (ORR) in the full analysis set assessed by the independent review committee (IRC) according to the Lugano Classification 2014. RESULTS: This study was prematurely terminated due to the slow rate of patient accrual. Between Oct 15th, 2018 and Oct 7th, 2020, 25 patients were enrolled and treated. By the data cutoff date on Dec 23rd, 2020, the IRC-assessed ORR was 68.0% (17/25; 95% confidence interval [CI] 46.5-85.1%), with the complete response rate of 24%. The disease control rate was 88% (22/25; 95%CI 68.8-97.5%). Median duration of response was not reached (NR) (95%CI, 5.62 months to NR), with 79.5% of patients having response durations of more than 12 months. Median progression-free survival was NR (95%CI, 6.83 months to NR). Treatment-related adverse events (TRAEs) were reported in 20 of 25 (80.0%) patients, and grade 3 or higher TRAEs occurred in 11 of 25 (44%) patients. No treatment-related deaths occurred. The immune-related adverse events (irAEs) of any grade were observed in 6 (24.0%) patients, and no grade 4 or grade 5 irAEs were reported. CONCLUSION: Geptanolimab (GB226) demonstrated promising efficacy and a manageable safety profile in Chinese patients with r/r PMBCL.