Multicenter phase 2 study of oral azacitidine (CC-486) plus CHOP as initial treatment for PTCL.

Peripheral T-cell lymphomas (PTCL) with T-follicular helper phenotype (PTCL-TFH) has recurrent mutations affecting epigenetic regulators, which may contribute to aberrant DNA methylation and chemoresistance. This phase 2 study evaluated oral azacitidine (CC-486) plus cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) as initial treatment for PTCL. CC-486 at 300 mg daily was administered for 7 days before C1 of CHOP, and for 14 days before CHOP C2-6. The primary end point was end-of-treatment complete response (CR). Secondary end points included safety and survival. Correlative studies assessed mutations, gene expression, and methylation in tumor samples. Grade 3 to 4 hematologic toxicities were mostly neutropenia (71%), with febrile neutropenia uncommon (14%). Nonhematologic toxicities included fatigue (14%) and gastrointestinal symptoms (5%). In 20 evaluable patients, CR was 75%, including 88.2% for PTCL-TFH (n = 17). The 2-year progression-free survival (PFS) was 65.8% for all and 69.2% for PTCL-TFH, whereas 2-year overall survival (OS) was 68.4% for all and 76.1% for PTCL-TFH. The frequencies of the TET2, RHOA, DNMT3A, and IDH2 mutations were 76.5%, 41.1%, 23.5%, and 23.5%, respectively, with TET2 mutations significantly associated with CR (P = .007), favorable PFS (P = .004) and OS (P = .015), and DNMT3A mutations associated with adverse PFS (P = .016). CC-486 priming contributed to the reprograming of the tumor microenvironment by upregulation of genes related to apoptosis (P < .01) and inflammation (P < .01). DNA methylation did not show significant shift. This safe and active regimen is being further evaluated in the ALLIANCE randomized study A051902 in CD30-negative PTCL. This trial was registered at www.clinicaltrials.gov as #NCT03542266.

GSDMD/Drp1 signaling pathway mediates hippocampal synaptic damage and neural oscillation abnormalities in a mouse model of sepsis-associated encephalopathy.

BACKGROUND: Gasdermin D (GSDMD)-mediated pyroptotic cell death is implicated in the pathogenesis of cognitive deficits in sepsis-associated encephalopathy (SAE), yet the underlying mechanisms remain largely unclear. Dynamin-related protein 1 (Drp1) facilitates mitochondrial fission and ensures quality control to maintain cellular homeostasis during infection. This study aimed to investigate the potential role of the GSDMD/Drp1 signaling pathway in cognitive impairments in a mouse model of SAE. METHODS: C57BL/6 male mice were subjected to cecal ligation and puncture (CLP) to establish an animal model of SAE. In the interventional study, mice were treated with the GSDMD inhibitor necrosulfonamide (NSA) or the Drp1 inhibitor mitochondrial division inhibitor-1 (Mdivi-1). Surviving mice underwent behavioral tests, and hippocampal tissues were harvested for histological analysis and biochemical assays at corresponding time points. Haematoxylin-eosin staining and TUNEL assays were used to evaluate neuronal damage. Golgi staining was used to detect synaptic dendritic spine density. Additionally, transmission electron microscopy was performed to assess mitochondrial and synaptic morphology in the hippocampus. Local field potential recordings were conducted to detect network oscillations in the hippocampus. RESULTS: CLP induced the activation of GSDMD, an upregulation of Drp1, leading to associated mitochondrial impairment, neuroinflammation, as well as neuronal and synaptic damage. Consequently, these effects resulted in a reduction in neural oscillations in the hippocampus and significant learning and memory deficits in the mice. Notably, treatment with NSA or Mdivi-1 effectively prevented these GSDMD-mediated abnormalities. CONCLUSIONS: Our data indicate that the GSDMD/Drp1 signaling pathway is involved in cognitive deficits in a mouse model of SAE. Inhibiting GSDMD or Drp1 emerges as a potential therapeutic strategy to alleviate the observed synaptic damages and network oscillations abnormalities in the hippocampus of SAE mice.

The Lymphoma Epidemiology of Outcomes cohort study: Design, baseline characteristics, and early outcomes.

To address the current and long-term unmet health needs of the growing population of non-Hodgkin lymphoma (NHL) patients, we established the Lymphoma Epidemiology of Outcomes (LEO) cohort study (NCT02736357; https://leocohort.org/). A total of 7735 newly diagnosed patients aged 18 years and older with NHL were prospectively enrolled from 7/1/2015 to 5/31/2020 at 8 academic centers in the United States. The median age at diagnosis was 62 years (range, 18-99). Participants came from 49 US states and included 538 Black/African-Americans (AA), 822 Hispanics (regardless of race), 3386 women, 716 age <40 years, and 1513 rural residents. At study baseline, we abstracted clinical, pathology, and treatment data; banked serum/plasma (N = 5883, 76.0%) and germline DNA (N = 5465, 70.7%); constructed tissue microarrays for four major NHL subtypes (N = 1189); and collected quality of life (N = 5281, 68.3%) and epidemiologic risk factor (N = 4489, 58.0%) data. Through August 2022, there were 1492 deaths. Compared to population-based SEER data (2015-2019), LEO participants had a similar distribution of gender, AA race, Hispanic ethnicity, and NHL subtype, while LEO was underrepresented for patients who were Asian and aged 80 years and above. Observed overall survival rates for LEO at 1 and 2 years were similar to population-based SEER rates for indolent B-cell (follicular and marginal zone) and T-cell lymphomas, but were 10%-15% higher than SEER rates for aggressive B-cell subtypes (diffuse large B-cell and mantle cell). The LEO cohort is a robust and comprehensive national resource to address the role of clinical, tumor, host genetic, epidemiologic, and other biologic factors in NHL prognosis and survivorship.

Dynamic Stereochemistry of M8 Pd6 Supramolecular Cages Based on Metal-Center Lability for Differential Chiral Induction, Resolution, and Recognition.

A series of isostructural supramolecular cages with a rhombic dodecahedron shape have been assembled with distinct metal-coordination lability (M8 Pd6 -MOC-16, M=Ru2+ , Fe2+ , Ni2+ , Zn2+ ). The chirality transfer between metal centers generally imposes homochirality on individual cages to enable solvent-dependent spontaneous resolution of Δ8 /Λ8 -M8 Pd6 enantiomers; however, their distinguishable stereochemical dynamics manifests differential chiral phenomena governed by the cage stability following the order Ru8 Pd6 >Ni8 Pd6 >Fe8 Pd6 >Zn8 Pd6 . The highly labile Zn centers endow the Zn8 Pd6 cage with conformational flexibility and deformation, enabling intrigue chiral-Δ8 /Λ8 -Zn8 Pd6 to meso-Δ4 Λ4 -Zn8 Pd6 transition induced by anions. The cage stabilization effect differs from inert Ru2+ , metastable Fe2+ /Ni2+ , and labile Zn2+ , resulting in different chiral-guest induction. Strikingly, solvent-mediated host-guest interactions have been revealed for Δ8 /Λ8 -(Ru/Ni/Fe)8 Pd6 cages to discriminate the chiral recognition of the guests with opposite chirality. These results demonstrate a versatile procedure to control the stereochemistry of metal-organic cages based on the dynamic metal centers, thus providing guidance to maneuver cage chirality at a supramolecular level by virtue of the solvent, anion, and guest to benefit practical applications.

Dynamic Metallosupramolecular Cages Containing 12 Adaptable Pockets for High-Order Guest Binding Beyond Biomimicry.

Molecular recognition lies at the heart of biological functions, which inspires lasting research in artificial host syntheses to mimic biomolecules that can recognize, process, and transport molecules with the highest level of complexity; nonetheless, the design principle and quantifying methodology of artificial hosts for multiple guests (≥4) remain a formidable task. Herein, we report two rhombic dodecahedral cages [(Zn/Fe)8Pd6-MOC-16], which embrace 12 adaptive pockets for multiguest binding with distinct conformational dynamics inherent in metal-center lability and are able to capture 4-24 guests to manifest a surprising complexity of binding scenarios. The exceptional high-order and hierarchical encapsulation phenomena suggest a wide host-guest dynamic-fit, enabling conformational adjustment and adaptation beyond the duality of induced-fit and conformational selection in protein interactions. A critical inspection of the host-guest binding events in solution has been performed by NMR and ESI-MS spectra, highlighting the importance of acquiring a reliable binding repertoire from different techniques and the uncertainty of quantifying the binding affinities of multiplying guests by an oversimplified method.

A phase 2 biomarker-driven study of ruxolitinib demonstrates effectiveness of JAK/STAT targeting in T-cell lymphomas.

Signaling through JAK1 and/or JAK2 is common among tumor and nontumor cells within peripheral T-cell lymphoma (PTCL). No oral therapies are approved for PTCL, and better treatments for relapsed/refractory disease are urgently needed. We conducted a phase 2 study of the JAK1/2 inhibitor ruxolitinib for patients with relapsed/refractory PTCL (n = 45) or mycosis fungoides (MF) (n = 7). Patients enrolled onto 1 of 3 biomarker-defined cohorts: (1) activating JAK and/or STAT mutations, (2) ≥30% pSTAT3 expression among tumor cells by immunohistochemistry, or (3) neither or insufficient tissue to assess. Patients received ruxolitinib 20 mg PO twice daily until progression and were assessed for response after cycles 2 and 5 and every 3 cycles thereafter. The primary endpoint was clinical benefit rate (CBR), defined as the combination of complete response, partial response (PR), and stable disease lasting at least 6 months. Only 1 of 7 patients with MF had CBR (ongoing PR > 18 months). CBR among the PTCL cases (n = 45) in cohorts 1, 2, and 3 were 53%, 45%, and 13% (cohorts 1 & 2 vs 3, P = .02), respectively. Eight patients had CBR > 12 months (5 ongoing), including 4 of 5 patients with T-cell large granular lymphocytic leukemia. In an exploratory analysis using multiplex immunofluorescence, expression of phosphorylated S6, a marker of PI3 kinase or mitogen-activated protein kinase activation, in <25% of tumor cells was associated with response to ruxolitinib (P = .05). Our findings indicate that ruxolitinib is active across various PTCL subtypes and support a precision therapy approach to JAK/STAT inhibition in patients with PTCL. This trial was registered at www.clincialtrials.gov as #NCT02974647.

Recurrence and survival of patients with stage III endometrial cancer after radical surgery followed by adjuvant chemo- or chemoradiotherapy: a systematic review and meta-analysis.

OBJECTIVE: To compare recurrence and survival in patients with stage III endometrial cancer after radical surgery, followed by either adjuvant chemoradiotherapy (ACR) or adjuvant chemotherapy (AC). METHODS: We searched for relevant studies in PubMed Central, Embase and the Cochrane Central Register of Controlled Trials. Data were pooled on rates of recurrence as well as rates of progression-free, disease-free and overall survival. Heterogeneity was evaluated using the I2 test. Subgroup and sensitivity analyses were performed to identify potential sources of heterogeneity. RESULTS: Data from 18,375 patients in 15 retrospective studies and one randomized controlled trial were meta-analyzed. Compared to the AC group, the ACR showed significantly lower risk of local recurrence (OR 0.43, 95%CI 0.32-0.59) and total recurrence (OR 0.72, 95%CI 0.58-0.89). ACR was also associated with significantly better overall survival (HR 0.66, 95%CI 0.57-0.76), progression-free survival (HR 0.56, 95%CI 0.39-0.81) and disease-free survival (HR 0.66, 95%CI 0.53-0.83). CONCLUSIONS: Adding adjuvant radiotherapy to adjuvant chemotherapy after radical surgery may significantly reduce risk of local and overall recurrence, while significantly improving survival of patients with stage III endometrial cancer.

Hematological Oncology journal women in lymphoma special issue: Latest updates in nodal peripheral T-cell lymphoma.

In the last decade, there has been increased understanding of the pathologic features and biology of peripheral T cell lymphomas (PTCLs) through development of multi omics and molecular profiling techniques. In addition, international collaborations through multi center trials as well as prospective registry studies have improved our knowledge of host and tumor genomic factors and treatment factors affecting disease outcomes. In our review today, we aim to highlight the current epidemiology, latest advances in classification, disease biology and the evolving treatment landscape for nodal PTCLs.

Angioimmunoblastic T-cell lymphoma presenting with severe plasmacytosis mimicking plasma cell leukemia.

Peripheral blood smear (A) demonstrates increased numbers of plasma cells (representative cells indicated by arrows), (B) demonstrates polytypic nature of plasma cells.

In vitro assays for investigating the FLASH effect.

FLASH radiotherapy is a novel technique that has been shown in numerous preclinical in vivo studies to have the potential to be the next important improvement in cancer treatment. However, the biological mechanisms responsible for the selective FLASH sparing effect of normal tissues are not yet known. An optimal translation of FLASH radiotherapy into the clinic would require a good understanding of the specific beam parameters that induces a FLASH effect, environmental conditions affecting the response, and the radiobiological mechanisms involved. Even though the FLASH effect has generally been considered as an in vivo effect, studies finding these answers would be difficult and ethically challenging to carry out solely in animals. Hence, suitable in vitro studies aimed towards finding these answers are needed. In this review, we describe and summarise several in vitro assays that have been used or could be used to finally elucidate the mechanisms behind the FLASH effect.

Intervalley Excitonic Hybridization, Optical Selection Rules, and Imperfect Circular Dichroism in Monolayer h-BN.

We perform first-principles GW plus Bethe-Salpeter equation calculations to investigate the photophysics of monolayer hexagonal boron nitride (h-BN), revealing excitons with novel k-space characteristics. The excitonic states forming the first and third peaks in its absorption spectrum are s-like, but those of the second peak are notably p-like, a first finding of strong co-occurrence of bright s-like and bright p-like states in an intrinsic 2D material. Moreover, even though the k-space wave function of these excitonic states are centered at the K and K^{'} valleys as in monolayer transition metal dichalcogenides, the k-space envelope functions of the basis excitons at one valley have significant extents to the basin of the other valley. As a consequence, the optical response of monolayer h-BN exhibits a lack of circular dichroism, as well as a coupling that induces an intervalley mixing between s- and p-like states.

Efficacy of Photodynamic Therapy for the Treatment of Bowen's Disease: A Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Photodynamic therapy is an established treatment option for Bowen's disease. Our meta-analysis was aimed at evaluating the efficacy and recurrence of photodynamic therapy or other topical treatments (5-fluorouracil, cryotherapy) and of photodynamic therapy alone or in combination with other therapies (ablative fractional CO2 laser or plum-blossom needle) for the treatment of Bowen's disease. METHODS: Trials that met our inclusion criteria were identified from PubMed, EMBASE, Web of Science, and Cochrane Library databases, and meta-analyses were conducted with RevMan V.5.4. The risk of bias was estimated with the Cochrane Collaboration's risk of bias tools. Complete response rate, recurrence, pain/visual analogue scale score, cosmetic outcome, and adverse events were considered as outcomes. RESULTS: Of the 2,439 records initially retrieved, 8 randomized controlled trials were included in this meta-analysis. According to our analyses, photodynamic therapy exhibited a significantly higher complete response rate (RR = 1.36, 95% CI [1.01, 1.84], I2 = 86%, p = 0.04), less recurrence (RR = 0.53, 95% CI [0.30, 0.95], I2 = 0%, p = 0.03), and better cosmetic outcome (RR = 1.34, 95% CI [1.15, 1.56], I2 = 0%, p = 0.0002) compared with other treatments. Moreover, there was a significant difference between the complete response rate of photodynamic therapy combined with ablative fractional CO2 laser and that of photodynamic therapy (RR = 1.85, 95% CI [1.38, 2.49], I2 = 0%, p < 0.0001). Photodynamic therapy combined with ablative fractional CO2 laser or plum-blossom needle also showed significantly less recurrence (RR = 0.21, 95% CI [0.09, 0.51], I2 = 0%, p = 0.0005) and a lower visual analogue scale score (RR = 0.51, 95% CI [0.06, 0.96], I2 = 0%, p = 0.03) than photodynamic therapy alone. However, there was no significant difference in the complete response rate between photodynamic therapy combined with ablative continuous CO2 laser and photodynamic therapy combined with ablative fractional CO2 laser (RR = 1.00, 95% CI [0.54, 1.86], I2 not applicable, p = 1.00). CONCLUSIONS: This meta-analysis shows that photodynamic therapy can be used in the treatment of Bowen's disease with better efficacy, less recurrence, and better cosmetic outcomes than cryotherapy and 5-FU. Some methods, including ablative fractional CO2 laser, can be applied in combination with photodynamic therapy to improve efficacy. However, which laser-assisted photodynamic therapy scheme has the most advantages in the treatment of Bowen's disease warrants further exploration.

An electrochemical aptasensor based on target triggered multiple-channel DNAzymes cycling amplification strategy with PtFe@Co-MOF as signal amplifier.

A novel electrochemical aptasensor for the detection of Aflatoxin B1 (AFB1) was developed for the first time by using the target-triggered multiple-channel deoxyribozymes (DNAzymes) cycling amplified assay with Pt Fe doped NH2-Co-MOF (PtFe@Co-MOF) as a signal amplifier. In the presence of AFB1, a self-assembling cross-over nucleic structure could be triggered by AFB1 via two aptamers' structure switching for strand displacement, resulting in four channels of Mg2+-dependent DNAzyme recycling simultaneously to multiply the detection signals. These DNAzymes cyclically split the substrate sequence to release the PtFe@Co-MOF labeled detection probe (DP), which is subsequently hybridized with the capture probes on the Au-deposited glassy carbon electrode. The fabrication procedure was characterized by differential pulse voltammetry, and the results of the morphological and element composition characteristics methods were analyzed to determine the successful preparation of PtFe@Co-MOF. The limit of detection (LOD) for AFB1 detection was 2 pg mL-1 with a linear range from 5 pg mL-1 to 80 ng mL-1. By comparison, the enhanced detection sensitivity has been found to originate from the efficient shearing of DNAzymes, enhanced peroxidase-like capability, and multiple active sites of PtFe@Co-MOF. Besides, this aptasensor showed high specificity for AFB1 compared with similar mycotoxins and exhibited high accuracy with low experimental cost and easy operation. Furthermore, the unique design of electrochemical aptasensors could provide a promising platform for the onsite determination of AFB1, as well as other targets by replacing the aptamer and other core recognition sequences.

Ibrutinib plus lenalidomide and rituximab has promising activity in relapsed/refractory non-germinal center B-cell-like DLBCL.

The outcome of patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) is poor, particularly in patients ineligible for stem cell transplantation or who fail induction therapy or salvage therapy. The phase 1b portion of this open-label, dose-escalation (3+3+3 design) study examined the maximum tolerated dose (MTD) and preliminary safety and activity of the regimen in transplant-ineligible adults with histologically confirmed relapsed/refractory DLBCL after at least 1 prior therapy. Patients received once-daily 560 mg ibrutinib, 375 mg/m2 intravenous rituximab day 1 of cycles 1 to 6, and 10, 15, 20, or 25 mg lenalidomide days 1 to 21 of each 28-day cycle. Forty-five patients were treated; median time since diagnosis was 14.1 months, and 51% of the patients had non-germinal center B-cell-like (non-GCB) DLBCL, 33% had transformed DLBCL, 60% were refractory, and 27% were primary refractory. Because of dose-limiting toxicities, a de-escalation cohort (10 mg lenalidomide) was initiated, and with subsequent re-escalation up to 25 mg lenalidomide, the MTD was not reached. In response-evaluable patients, the overall response rate (ORR) was 44% (complete response [CR], 28%); among them, the ORR was 65% (CR, 41%) in non-GCB and 69% and 56% in relapsed (n = 16) and secondary refractory (n = 27) disease, respectively. Overall and for non-GCB, median response duration was 15.9 months, with 2 patients receiving therapy beyond 3 years. Phase 2 was initiated with 20 mg lenalidomide in relapsed/refractory non-GCB, whereas the phase 1b 25-mg lenalidomide cohort was being completed; an additional 25-mg cohort in phase 2 is currently ongoing. This study was registered at www.clinicaltrials.gov as #NCT02077166.

A phase 1 trial of ibrutinib plus palbociclib in previously treated mantle cell lymphoma.

Single-agent ibrutinib is active in patients with previously treated mantle cell lymphoma (MCL); however, nearly half of all patients experience treatment failure during the first year. We previously demonstrated that prolonged early G1 cell cycle arrest induced by the oral, specific CDK4/6 inhibitor palbociclib can overcome ibrutinib resistance in primary human MCL cells and MCL cell lines expressing wild-type Bruton's tyrosine kinase (BTK). Therefore, we conducted a phase 1 trial to evaluate the dosing, safety, and preliminary activity of palbociclib plus ibrutinib in patients with previously treated mantle cell lymphoma. From August 2014 to June 2016, a total of 27 patients (21 men, 6 women) were enrolled. The maximum tolerated doses were ibrutinib 560 mg daily plus palbociclib 100 mg on days 1 to 21 of each 28-day cycle. The dose-limiting toxicity was grade 3 rash. The most common grade 3 to 4 toxicities included neutropenia (41%), thrombocytopenia (30%), hypertension (15%), febrile neutropenia (15%), and lung infection (11%). The overall and complete response rates were 67% and 37%, and with a median follow-up of 25.6 months, the 2-year progression-free survival was 59.4% and the 2-year response duration was 69.8%. A phase 2 multicenter clinical trial to further characterize efficacy is now ongoing. The current trial was registered at www.clinicaltrials.gov as #NCT02159755.

Autologous EBV-specific T cell treatment results in sustained responses in patients with advanced extranodal NK/T lymphoma: results of a multicenter study.

We conducted a phase II clinical trial to develop an autologous EBV-specific T cell product (baltaleucel T) for advanced, relapsed ENKTL. Among 47 patients who provided whole blood starting material for manufacturing the product, 15 patients received a median of 4 doses of baltaleucel T. Thirty-two (68%) patients did not receive baltaleucel-T due to manufacturing failure, rapid disease progression, and death. Of the 15 patients, 10 patients had measurable disease at baseline (salvage cohort), and 5 patients had no disease at baseline assessment (adjuvant cohort). In the 15 patients, the median follow-up duration was 10.2 months (range 2.0-23.5 months), median progression-free survival (PFS) was 3.9 months, and the median overall survival (OS) was not reached. Patients in the salvage cohort achieved a 30% complete response (CR) and a 50% overall response rate (ORR). In the adjuvant cohort, disease progression was reported in three patients and two patients did not relapse during study follow-up. When we compared survival outcomes of seven responders and eight non-responders, the PFS (P = 0.001) and OS (P = 0.014) of responders proved statistically superior to that of non-responders. Baltaleucel-T was well tolerated. We have performed a phase II clinical trial of autologous EBV-specific T cell treatment (baltaleucel-T) in R/R ENKTL. Autologous EBV-specific T cells were well tolerated and demonstrated single-agent activity in R/R ENTKL.

Romidepsin and lenalidomide-based regimens have efficacy in relapsed/refractory lymphoma: Combined analysis of two phase I studies with expansion cohorts.

Romidepsin (histone deacetylase inhibitor), lenalidomide (immunomodulatory agent), and carfilzomib (proteasome inhibitor), have efficacy and lack cumulative toxicity in relapsed/refractory lymphoma. We performed two investigator initiated sequential phase I studies to evaluate the maximum tolerated dose (MTD) of romidepsin and lenalidomide (regimen A) and romidepsin, lenalidomide, and carfilzomib (regimen B) in relapsed/refractory lymphoma. Cohorts in T-cell lymphoma (TCL), B-cell lymphoma (BCL) were enrolled at the MTD. Forty-nine patients were treated in study A (27 TCL, 17 BCL, 5 Hodgkin lymphoma (HL)) and 27 (16 TCL, 11 BCL) in study B. The MTD of regimen A was romidepsin 14 mg/m2 IV on days 1, 8, and 15 and lenalidomide 25 mg oral on days 1-21 of a 28-day cycle. The MTD of regimen B was romidepsin 8 mg/m2 on days 1 and 8, lenalidomide 10 mg oral on days 1-14 and carfilzomib 36 mg/m2 IV on days 1 and 8 of a 21-day cycle. In study A, 94% had AEs ≥Grade 3, most commonly neutropenia (49%), thrombocytopenia (53%), and electrolyte abnormalities (49%). In study B 59% had AEs ≥Grade 3, including thrombocytopenia (30%) and neutropenia (26%). In study A the ORR was 49% (50% TCL, 47% BCL, 50% HL). In study B the ORR was 48% (50% TCL, 50% BCL). For study A and B the median progression free survival (PFS) was 5.7 months and 3.4 months respectively with 11 patients proceeding to allogeneic transplant. The combinations of romidepsin and lenalidomide and of romidepsin, lenalidomide and carfilzomib showed activity in relapsed/refractory lymphoma with an acceptable safety profile.

Multi-Mode Color-Tunable Long Persistent Luminescence in Single-Component Coordination Polymers.

Materials with tunable long persistent luminescence (LPL) properties have wide applications in security signs, anti-counterfeiting, data encrypting, and other fields. However, the majority of reported tunable LPL materials are pure organic molecules or polymers. Herein, a series of metal-organic coordination polymers displaying color-tunable LPL were synthesized by the self-assembly of HTzPTpy ligand with different cadmium halides (X=Cl, Br, and I). In the solid state, their LPL emission colors can be tuned by the time-evolution, as well as excitation and temperature variation, realizing multi-mode dynamic color tuning from green to yellow or green to red, and are the first such examples in single-component coordination polymer materials. Single-crystal X-ray diffraction analysis and theoretical calculations reveal that the modification of LPL is due to the balanced action from single molecule and aggregate triplet excited states caused by an external heavy-atom effect. The results show that the rational introduction of different halide anions into coordination polymers can realize multi-color LPL.

Five-year follow-up of lenalidomide plus rituximab as initial treatment of mantle cell lymphoma.

We report 5-year follow-up of a multicenter phase 2 study of lenalidomide plus rituximab (LR) as initial treatment of mantle cell lymphoma (MCL). The regimen includes induction and maintenance with the LR doublet. Treatment was continuous until progression, with optional discontinuation after 3 years. The median age of the 38 participants was 65 years, with MCL international prognostic index scores balanced among low, intermediate, and high risk (34%, 34%, and 32%, respectively). Twenty-seven (75%) of the 36 evaluable patients completed ≥3 years of study treatment. At a median follow-up of 64 months (range, 21-78), the 3-year progression-free survival (PFS) and overall survival (OS) were 80% and 90%, respectively, with 5-year estimated PFS and OS of 64% and 77%, respectively. During maintenance, hematologic adverse events (AEs) included asymptomatic grade 3 or 4 cytopenias (42% neutropenia, 5% thrombocytopenia, 3% anemia) and mostly grade 1 or 2 infections managed in the outpatient setting (45% upper respiratory infection, 21% urinary tract infection, 13% sinusitis, 11% cellulitis, 8% pneumonia). Nonhematologic AEs, such as constitutional and inflammatory symptoms, occurred at reduced frequency and intensity compared with induction. A peripheral blood minimal residual disease (MRD) assay (clonoSEQ) showed MRD-negative complete remission in 8 of 10 subjects who had completed ≥3 years of treatment and with available samples for analysis. With longer follow-up, LR continues to demonstrate durable responses and manageable safety as initial induction and maintenance therapy for MCL (ClinicalTrials.gov NCT01472562).

Enhanced Long Persistent Luminescence by Multifold Interpenetration in Metal-Organic Frameworks.

Metal-organic frameworks (MOFs) with long persistent luminescence (LPL) have attracted widespread attention due to potential applications in displays, anticounterfeiting, and so on. However, MOFs often have large pore size, which restricts the formation of efficient inter- and intramolecular interactions to realize LPL. Herein, a new approach to achieving LPL in MOFs by multifold interpenetration of discrete frameworks is reported. By comparison between threefold- and twofold-interpenetrating MOFs, it was found that the former, which have higher multiplicity and denser frameworks, can be endowed with enhanced inter- and intramolecular interactions, and thus enhanced LPL is obtained. Meanwhile, metal-cluster and heavy-halogen effects could also cause variations in LPL duration and color.