CR Rate Research Articles

The influence of the pre-addition of semi-dry and dry slaked lime during the purification of flue gas on the subsequent chelation and solidification treatment of MSWI fly ash

Incineration is a main way to dispose the municipal solid waste (MSW) in China, but municipal solid waste incineration (MSWI) fly ash will negatively impact the environment and human health as containing high content of heavy metals. This study aimed to investigate the influence of the pre-addition of dry/semi-dry slaked lime during the purification of flue gas on the subsequent chelation and solidification treatment of fly ash. This study has found that semi-dry slaked lime had more effect on the solidification rate of heavy metals in MSWI fly ash compared to the pre-addition of the dry slaked lime. As the dosage of semi-dry slaked lime increased, the solidification rate of Zn and Ba increased to 100 %, while the solidification rate of Cr decreased to as low as 0 %. However, the effect of the dosage of semi-dry slaked lime on the other heavy metals (Cu, Pb, Cd, Ni) showed a complex trend. This study underscores the importance of the pre-addition of slaked lime during the purification of flue gas in influencing subsequent chelation and solidification treatment of MSWI fly ash. It provides valuable insights into optimizing lime dosage to enhance heavy metal stabilization, contributing to more effective and sustainable waste management practices.

AQDS-functionalized biochar enhances the bioreduction of Cr(VI) by Shewanella putrefaciens CN32

The bioreduction of toxic chromium(VI) to sparingly soluble chromium(III) represents an environmentally friendly and cost-effective method for remediating Cr contamination. Usually, this bioreduction process is slow and requires the addition of quinone compounds as electron shuttles to enhance the reaction rate. However, the dissolved quinone compounds are susceptible to loss with water flow, thereby limiting their effectiveness. To address this challenge, this study loaded anthraquinone-2,6-disulfonate (AQDS), a typical quinone compound, onto biochar (BC) to create a novel solid-phase electron mediator (BC-AQDS) that can sustainably promote Cr(VI) bioreduction. The experimental results demonstrated that BC-AQDS significantly promoted the bioreduction of Cr(VI), where the reaction rate constant increased by 4.81 times, and the reduction extent increased by 38.31%. X-ray photoelectron spectroscopy and Fourier-Transform Infrared Spectroscopy analysis revealed that AQDS replaced the –OH functional groups on the BC surface to form BC-AQDS. Upon receiving electrons from Shewanella putrefaciens CN32, BC-AQDS was reduced to BC-AH2DS, which subsequently facilitated the reduction of Cr(VI) to Cr(III). This redox cycle between BC-AQDS and BC-AH2DS effectively enhanced the bioreduction rate of Cr(VI). Our study also found that a lower carbonization temperature of BC resulted in a higher surface –OH functional group content, enabling a greater load of AQDS and a more pronounced enhancement effect on the bioreduction of Cr(VI). Additionally, a smaller particle size of BC and a higher dosage of BC-AQDS further contributed to the enhancement of Cr(VI) bioreduction. The preparation of BC-AQDS in this study effectively improve the utilization of quinone compounds and offer a promising approach for enhancing the bioreduction of Cr(VI). It provides a more comprehensive reference for understanding and solving the problem of Cr pollution in groundwater.

Efficient removal of Chromium(VI) from wastewater based on magnetic multiwalled carbon nanotubes coupled with deep eutectic solvents

Industrial wastewater containing heavy metal Cr(VI) seriously affects the health of organisms and may even lead to cancer. Developing efficient adsorbents that can quickly separate heavy metals is crucial for treating wastewater. In this study, magnetic multiwalled carbon nanotubes (MMWCNTs) with moderate particle size and abundant surface active sites were prepared by coating multiwalled carbon nanotubes with magnetic nanoparticles. The results of FTIR, XRD, TG, VSM, BET, and EDS showed MWCNTs completely encapsulated on the surface of the magnetic nanoparticles, with a particle size of approximately 30 nm. Oxygenated groups provided abundant surface active sites and formed numerous mesopores. The response surface methodology was used to optimize the adsorbent dose, adsorption contact time and adsorption temperature, and the removal rate of Cr(VI) was more than 95%. The quasi-second order kinetics and Freundlich adsorption isotherm model explained the adsorption process to Cr(VI). MMWCNTs interacted with Cr(VI) through electrostatic attraction, reduction reactions, complexation, and other means. The extensive hydrogen bonding of the green solvent deep eutectic solvent (DES) was employed to desorb the MMWCNTs and desorption rate exceed 90%. Even after five adsorption-regeneration cycles, the adsorbent maintained a high capacity. In conclusion, these novel MMWCNTs, as efficient adsorbents paired with DES desorption, hold broad potential for application in the treatment of Cr(VI)-contaminated wastewater.

Polyoxometalate Functionalized Cyclic Trinuclear Copper Compounds for Bifunctional Electrochemical Detection and Photocatalytic Reduction of Cr(VI).

The design and intentional construction of crystalline materials containing two clusters with redox properties in one framework still remains challenging. Linking oxidative polyoxometalate (POM) clusters and a reductive cyclic trinuclear copper complex (Cu-CTC) to prepare stable catalysts is rarely reported. Herein, we successfully obtained two new polyoxometalate-based metal-organic compounds (POMOCs) [CuII3(PyCA)3(μ3-OH)(β-Mo8O26)0.5(H2O)2]·5H2O (1), [CuII3(PyCA)3(μ3-OH)]2(CuIIW12O40)[CuII(H2O)6] (2) (PyCA = 1H-pyrazole-4-carbaldehyde) by enabling precursors of Cu-CTC and POM cocrystallization in one pot via hydrothermal method. The [β-Mo8O26]4- cluster in compound 1 combined with Cu-CTC units to form a 1D structure, and the [CuW12O40]6- unit in compound 2 linked two Cu-CTC units to form a sandwich-like 0D structure. Also, Cu-CTC CuI3(PyCA)3·H2O (Cu3) was synthesized for performance comparison. A series of characterizations indicate that compound 1 is more conducive to electron transfer than compound 2. In addition, compounds 1 and 2 can act as bifunctional catalysts for the electrochemical detection and photocatalytic reduction of Cr(VI). Particularly, the photoreduction rates of Cr(VI) by compounds 1 and 2 are 96.7% and 96.3% for only 10 and 14 min under visible light, respectively, and it is better than that of Cu3 and most other reported photocatalysts. Furthermore, the active sites and mechanisms for electrochemical detection and photocatalytic reduction of Cr(VI) were discussed.

Bispecific Antibodies for the Management of Relapsed/Refractory Multiple Myeloma.

Bispecific antibodies (BsAbs) are artificially engineered antibodies that can bind simultaneously to the CD3 subunit within the T-cell receptor complex and an antigen on tumor cells, leading to T-cell activation and tumor cell killing. BsAbs against BCMA or GPRC5D have shown impressive clinical activity in heavily pretreated patients with relapsed/refractory multiple myeloma (RRMM), with some agents having already received regulatory approval after the third (by the European Medicines Agency, EMA) or fourth (by the Food and Drug Administration, FDA) line of therapy; the results of early-phase clinical trials targeting FcRH5 are also promising. Overall, BsAbs as monotherapy correlated with an ORR that exceeded 60%, with a high CR rate ranging between 25% and 50% and a median PFS of around 1 year among patients with a median of 4-6 prior lines of therapy. The main toxicities include cytokine release syndrome, cytopenias, hypogammaglobulinemia, and infections; on-target off-tumor adverse events involving the skin, mucosa, hair, and nails may also occur with anti-GPRC5D BsAbs. Active research to increase their efficacy and improve their tolerance is still in progress, including combination therapies and application in earlier treatment lines and the development of novel agents. A better understanding of the mechanisms of resistance is a challenge and could lead to more personalized approaches.

Rationally designed β-FeOOH/N,P-MXene Schottky-junction for efficient removal of pollutants from wastewater

Effective separation of photogenerated electrons and holes, as well as providing ample reactive sites, is crucial for enhancing the activity of photocatalytic degradation of pollutants in water. In this study, we have expanded MXene through a simple water swelling method and successfully doped N and P elements into MXene via a hydrothermal process. This modification not only exfoliates the layered structure of MXene, enlarging its specific surface area and providing abundant reactive sites but also endows MXene with enhanced metallic properties. As a result, an N,P-MXene/FeOOH Schottky junction photocatalyst is constructed. Our photocatalytic experiments revealed that the FO-NPM200/H2O2 system performs well under extreme pH conditions and exhibits excellent photocatalytic stability across a wide pH range (1–13), suggesting its outstanding potential for practical applications in complex environments. Under conditions of pH = 7 without the presence of inorganic salt ions, the degradation rate of tetracycline reached 98.1 %, and the photocatalytic reduction rate of the common heavy metal salt Cr(VI) was as high as 99.4 %. We have also unveiled the band structure of FO-NPM200 using UPS and UV–vis DRS. This research paves a new way for the design and construction of Schottky junction photocatalysts.

The enhanced effect of key microorganisms in chromium contaminated soil in Cr(VI) reduction

The escalating threat of Cr(VI) pollution to the environment and human health can be effectively controlled through microbial methods, which are promising, safe, and ecofriendly. To enhance Cr(VI) removal efficiency, scholars have been optimizing strains. However, synergies between in-situ soil particles and crucial microorganisms in soil have rarely been investigated. In this study, Cr(VI) was removed by collaborating with in-situ soil particles and key microorganisms in the soil. The results indicated that within 48 hours, the removal rate of Cr(VI) reached over 99% in the soils+microflora system, which was 45% higher than that of the microflora system alone. Factors such as Cr(VI) concentration, soil dosage, pH level, oxygen availability, and electron donors influenced the removal efficiency of Cr(VI) in the soils+microflora system. The cyclic experiments showed that soil particles effectively prevented chromium invasion on microflora, promoting the growth of crucial microorganisms. The addition of microflora can effectively regulate the composition of soil flora and enhance the efficiency of chromium reduction. Moreover, two strains each of Ochrobactrum sp. and Paenarthrobacter sp., exhibiting remarkable tolerance to Cr(VI), were successfully isolated from these soils, significantly enhancing the reduction capacity of the indigenous microflora towards Cr(VI). Additionally, 16S rRNA-PCR sequence analysis revealed that in-situ soil particles not only synergistically collaborated with the resident microflora for efficient removal of Cr(VI), but also facilitated the proliferation of key microbiota such as Ochrobactrum sp. and Paenarthrobacter sp. Remarkably, when exposed to an initial concentration of 50 mg/L Cr(VI), complete removal was achieved by Paenarthrobacter-2 within a time frame as short as 60 hours. This research found four novel highly efficient strains for reducing Cr(VI) and provides an innovative method for the synergistic interaction between indigenous soil microflora and soil particles to remove heavy metal ions from wastewater.

Mechanisms and influential factors of soil chromium long-term stability by an accelerated aging system after chemical stabilization

Chemical stabilization is one of the most widely used remediation strategies for chromium (Cr)-contaminated soils by reducing Cr(VI) to Cr(III), and its performance is affected by human and natural processes in a prolonged period, challenging long-term Cr stability. In this work, we established a method for evaluating the long-term effectiveness of remediation of Cr-contaminated soils, and developed an accelerated aging system to simultaneously simulate acid rain leaching and freeze-thaw cycles. The mechanisms and influencing factors of long-term (50-year) change in soil Cr speciation were unravelled after stabilization with Metafix®. Chemical stabilization remarkably decreased the contents of Cr(VI)soil, Crtotal-leach and Cr(VI)leach, among which the removal rate of Cr(VI) in soil was up to 89.70 %, but it also aggravated soil Cr instability. During the accelerated aging process, Crtotal-leach change rates in chemically stabilized soil samples were 0.0462–0.0587 mg/(L·a), and soil Cr became instable after 20-year accelerated aging. The proportion of Cr bound to organic matter and residual Cr increased in soil, and exchangeable Cr decreased. Linear combination fitting results of XANES also showed that Cr(VI) and Cr3+ were transformed into OM-Cr(III), Fh-Cr(III) and CrFeO3 after restoration. During the accelerated aging process, acid rain leaching activated Cr(III) and dissolved Cr(VI), whereas freeze-thaw cycle mainly affected OM-Cr. Chemical stabilization, acid rain leaching and aging time were the major factors influencing the stability of soil Cr, and the freeze-thaw cycle promoted the influence of acid rain leaching. This study provided a new way to explore the long-term effectiveness and instability mechanisms at Cr-contaminated site after chemical stabilization.

IMPACT OF DIFFERENT ORGANIC AND INORGANIC AMENDMENTS ON GROWTH AND YIELD OF MUNG BEAN IRRIGATED WITH TEXTILE EFFLUENTS

Water is an important substance for all life on earth, and it is essential for human beings, financial improvement, and the existence of ecological units. The quality and quantity of the water supply is very important, especially during irrigation. Due to the extensive measurement of water and colour associated with the manufacturing process, textile printing, and dyeing production lines around the world pose a major environmental risk. Textile wastewater contains a lot of pollutants including pH, temperature, shade, COD, BOD, TSS, TDS, EC, and heavy metals. This textile runoff continues to irrigate agricultural land, causing contamination of soils and plant systems with heavy metals. Therefore, adding organic and inorganic modifiers to soil is an effective technique for fixing heavy metals. Irrigate pots with textile wastewater of selected concentrations (10%, 25%, 50%, and 100%) collected in specific industrial sectors. The parameters of vegetative growth are reduced by increasing the concentration of textile effluent. Note the substantial reduction in the growth of plants applying wastewater at 100% concentration. In the case of T5, a significant increase in growth parameters was observed, where only tap water was used to pressurize the sludge, while dilute wastewater also enhanced growth at concentrations of 10% and 25%. For the chlorophyll content of mung bean plants, when the wastewater concentration is 100%, the recorded decrease is greater, followed by 10% and 25% respectively. The presence of heavy metals in wastewater reduces plant growth. In the experiment, all four treatments contained organic amendments (pressed sludge, poultry manure, biogas slurry, and farmyard manure). The other four treatment methods are pressure treatment of textile wastewater and the amount of organic modifier is 2%. By adding a correcting agent, the utilization rate of Cr is reduced, as the correcting agent will increase the pH of the soil, thus reducing the solubility of the metal. In addition, Cr can form insoluble complexes with organic materials, thus reducing its solubility.

Phase I Trial of Brentuximab Vedotin Plus Cyclosporine in Relapsed/Refractory Hodgkin Lymphoma

IntroductionBV is an antibody-drug conjugate directed against CD30 and is safe and effective in relapsed/refractory (R/R) Hodgkin lymphoma (HL). Most patients with r/r cHL respond well to BV monotherapy; however, the large of majority of them eventually progress on this drug, and BV-resistant HL remains an unmet need. Preclinical data suggest that BV resistance is mediated at least in part by increased drug efflux associated with increased expression of multidrug resistance pump 1 (MDR1) while CD30 expression appears to be preserved in BV resistant cell lines and patient samples. We conducted a phase 1 study evaluating BV + cyclosporine (CsA) in BV-refractory HL and previous reported results in the dose finding cohort. Here we report the final results from the phase 1 study. MethodsThis was a phase I trial of BV + CsA in patients with r/r HL with dose-finding and dose escalation cohorts. Eligibility criteria included age ≥ 18 years with r/r HL after at least 1 prior line of therapy. Treatment consisted of 1.8 mg/kg BV intravenously on day 1 and CsA 5 to 7.5 mg/kg PO twice daily on days 1 to 5; cycles were 21 days long. Patients in the expansion cohort had to have cHL refractory to BV. The primary objectives were to evaluate safety and tolerability and to determine MTD of BV + CsA; the secondary objective was to determine efficacy of this combination. Results29 patients were enrolled onto the study, 14 in the dose finding cohort and 15 in the dose expansion BV refractory cohort. Study accrual was terminated before target accrual due to unacceptable toxicity. 62% of patients were male, and the median age was 36 years (range: 20-69). The median number of prior therapies was 5 (range: 3-12); all patients had prior BV, and 93% had PD-1 directed therapy, and 93% were BV-refractory. Of 22 evaluable patients, CR rate was 27% and ORR 64%; median DOR 4.9 months. Treatment-related deaths occurred in 3 patients, and another patient died during cycle 1 due to cardiac arrest deemed unlikely related to be protocol therapy. All grade GI toxicity was seen in 90% of patients (G3+ in 24%); other common adverse events were nausea (90%), hypertension (90%), nausea (90%), hypertension (90%), anemia (86%), fatigue (76%), neutropenia (76%), leukopenia (76%), hypomagnesemia (76%), anorexia (66%), and hyponatremia (66%). DiscussionBV + CsA demonstrated modest activity in BV-refractory r/r HL; however, toxicity is substantial.

Olanzapine Plus Triple Antiemetic Therapy for the Prevention of Carboplatin-Induced Nausea and Vomiting: A Randomized, Double-Blind, Placebo-Controlled Phase III Trial.

We evaluated the efficacy and safety of antiemetic therapy with olanzapine, a neurokinin-1 receptor antagonist (RA), a 5-hydroxytryptamine-3 (5-HT3) RA, and dexamethasone for preventing chemotherapy-induced nausea and vomiting in patients receiving carboplatin-containing chemotherapy. Chemotherapy-naïve patients scheduled to receive carboplatin (AUC ≥5) were randomly assigned to receive either olanzapine 5 mg once daily (olanzapine group) or placebo (placebo group) in combination with aprepitant, a 5-HT3 RA, and dexamethasone. The primary end point was the complete response (CR; no vomiting and no rescue therapy) rate in the overall phase (0-120 hours). Secondary end points included the proportion of patients free of nausea and safety. In total, 355 patients (78.6% male, median age 72 years, 100% thoracic cancer), including 175 and 180 patients in the olanzapine and placebo groups, respectively, were evaluated. The overall CR rate was 86.9% in the olanzapine group versus 80.6% in the placebo group. The intergroup difference in the overall CR rate was 6.3% (95% CI, -1.3 to 13.9). The proportions of patients free of chemotherapy-induced nausea in the overall (88.6% in the olanzapine group v 75.0% in the placebo group) and delayed (89.7% v 75.6%, respectively) phases were significantly higher in the olanzapine group than in the placebo group (both P < .001). Somnolence was observed in 43 (24.6%) and 41 (22.9%) patients in the olanzapine and placebo groups, respectively, and no events were grade ≥3 in severity. The addition of olanzapine was not associated with a significant increase in the overall CR rate. Regarding the prevention of nausea, adding olanzapine provided better control in patients receiving carboplatin-containing chemotherapy, which needs further exploration.

Porous carbon nanofiber/porphyrin-based metal organic frameworks/TiO2 nanoparticles ternary materials for selective detection and photoreduction of Cr(Ⅵ)

For the heavy metal ion Cr(Ⅵ), which is widely present in wastewater with acute toxicity, mutagenicity and carcinogenicity, we successfully constructed a ternary material of PCNFs/CuMOF/TiO2 for rapid detection and photoreduction of Cr(Ⅵ). The material has obvious advantages: on the one hand, ZIF-8/polyacrylonitrile (PAN) nanofibers and their derived porous carbon nanofibers (PCNFs) were synthesized by electrospinning and high temperature carbonization, which provided a loading platform for CuMOF and TiO2, effectively inhibited the agglomeration of CuMOF and TiO2, and ensured the exposure of active sites. Meanwhile, its excellent conductivity can promote the effective migration of photogenerated carriers in the photocatalytic process. On the other hand, CuMOF constructed with tetra-carboxyphenylporphyrin (TCPP) as the linking arm and Cu(NO3)2·3 H2O as the metal node was directly loaded on the surface of porous carbon nanofibers (PCNFs), and then TiO2 nanoparticles were introduced by hydrothermal method. CuMOF ensures the responsiveness of the composite to visible light. Moreover, the energy level structure of TiO2 matches with CuMOF, which effectively inhibits the recombination of photogenerated electron-hole pairs (e--h+). The results show that the colorimetric detection of Cr(Ⅵ) was achieved by using 3,3′,5,5′-tetramethylbenzidine (TMB) as the sensing probe. The method was highly selective for Cr(Ⅵ) ions with a limit of detection (LOD) of 24.1 nM. Encouragingly, PCNFs/CuMOF/TiO2 was further used as a photocatalyst. The reduction rate of Cr(Ⅵ) under visible light irradiation is 96.1 % in 60 min. The active species trapping experiments confirm the key role of e- photocatalytic reduction, upon which a possible photocatalytic mechanism is proposed. The degradation rate of Cr(Ⅵ) is still 86.4 % after the five times cycle, and the good stability and reproducibility allow it to be used as a potential green photocatalyst for the conversion of Cr(Ⅵ) to Cr(Ⅲ).

Simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) combined with nimotuzumab for locally advanced esophageal squamous cell carcinoma (ESCC): A phase II clinical trial

ObjectiveTo evaluate the feasibility, safety and efficacy of concurrent simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) combined with nimotuzumab in the treatment of locally advanced esophageal squamous cell cancer (ESCC).MethodsEligible patients were histologically proven to have locally advanced ESCC, and were unable to tolerate or refuse concurrent chemoradiotherapy (CCRT). Enrolled patients underwent concurrent SIB-IMRT in combination with nimotuzumab. SIB-IMRT: For the planning target volume of clinical target volume (PTV-C), the prescription dose was 50.4 Gy/28fractions, 1.8 Gy/fraction, 5fractions/week, concurrently, the planning target volume of gross tumor (PTV-G) undergone an integrated boost therapy, with a prescription dose of 63 Gy/28fractions, 2.25 Gy/fraction, 5 fractions/week. Nimotuzumab was administered concurrently with radiotherapy, 200 mg/time, on D1, 8, 15, 22, 29, and 36, with a total accumulation of 1200 mg through intravenous infusion. The primary endpoint of the study was the safety and efficacy of the combined treatment regimen, and the secondary endpoints were 1-year, 2-year, and 3-year local control and survival outcomes.Results(1) From December 2018 to August 2021, 35 patients with stage II-IVA ESCC were enrolled and 34 patients completed the full course of radiotherapy and the intravenous infusion of full-dose nimotuzumab. The overall completion rate of the protocol was 97.1%. (2) No grade 4–5 adverse events occurred in the entire group. The most common treatment-related toxicity was acute radiation esophagitis, with a total incidence of 68.6% (24/35). The incidence of grade 2 and 3 acute esophagitis was 25.7% (9/35) and 17.1% (6/35), respectively. The incidence of acute radiation pneumonitis was 8.6% (3/35), including one case each of Grades 1, 2, and 3 pneumonitis. Adverse events in other systems included decreased blood cells, hypoalbuminemia, electrolyte disturbances, and skin rash. Among these patients, five experienced grade 3 electrolyte disturbances during the treatment period (three with grade 3 hyponatremia and two with grade 3 hypokalemia). (3) Efficacy: The overall CR rate was 22.8%, PR rate was 71.4%, ORR rate was 94.2%, and DCR rate was 97.1%.(4) Local control and survival: The 1-, 2-, and 3-year local control (LC) rate, progression-free survival(PFS) rate, and overall survival(OS) rate for the entire group were 85.5%, 75.4%, and 64.9%; 65.7%, 54.1%, and 49.6%; and 77.1%, 62.9%, and 54.5%, respectively.ConclusionsThe combination of SIB-IMRT and nimotuzumab for locally advanced esophageal cancer demonstrated good feasibility, safety and efficacy. It offered potential benefits in local control and survival. Acute radiation esophagitis was the primary treatment-related toxicity, which is clinically manageable. This comprehensive treatment approach is worthy of further clinical exploration (ChiCTR1900027936).

Outcome of patients with primary CNS lymphoma treated with methotrexate based regimens: A retrospective study.

e19051 Background: Primary central Nervous system Lymphoma is an aggressive Non-Hodgkins Lymphoma with 5-year survival of only 30 percent. Few studies have addressed the comparison of induction treatment regimens with various risk stratification groups with no consensus on the optimal methotrexate dose for best complete overall response and survival outcome. Our retrospective study compares induction treatment regimens, identifies different risk stratification factors, and provides insight into the best induction treatment regimen with determination of optimal methotrexate dose. Methods: Design: Retrospective Primary Outcomes: Complete response rate, overall survival rate with risk stratification based on histology, Ki-67, and initial albumin level. Results: 77 patients 18 years of age and older with PCNSL at NCC and LAC between June 2015 and July 2022 were included in the study. Overall, 50% of patients were treated with CALGB50202 induction regimen,19% with R-MPV,12 % with De-Angelis regimen. CALGB 50202 has the highest survival rate of 63.4% followed by R-MPV with 22% survival rate followed by De-Angelis regimen with 0% survival rate with chi-square test P-value &lt; 0.001 during the study period. Similarly, CALGB 50202 has the highest CR rate of 61.9% followed by R-MPV with CR rate of 16% followed by De-Angelis regimen with the lowest CR rate of 2.4%.CR rate comparison is statistically significant with P-value of &lt; 0.0001. The study assessed optimum methotrexate dose. The mean and median total methotrexate dose in patients who were alive during the study period was 74.3 grams and 81.7 grams respectively as compared to mean value of 34.2 grams and median of 19.3 grams in patients who died with a p-value of 0.0019.Comparing survival based on histology as germinal center versus non-germinal center PCNSL, the later has higher mortality rate of 64.7 % as compared to 11.8 % in patient with germinal center PCNSL.Ki-67 was assessed as &gt;80% and &lt;80%.Among patients who were alive during the study period,48.8% have Ki-67 &gt; 80% as compared to only 12.2%.On the other hand, among the patients who died,47.1% of patients have Ki-67 &lt;80%,indicating lower ki-67 associated a lower survival outcome as depicted on the Kaplan Meier curve with P-value of 0.004. Patients with normal initial albumin have a higher chance of survival (78%) vs 22% in the group with low albumin level with p-value of 0.0005. Conclusions: CALGB 50202 had the highest CR and survival rates followed by R-MPV regimen in patients with primary CNS lymphoma. The total dose of methotrexate patient receives was an important factor for survival and CR and the optimal total methotrexate dose was 70-80 grams. Normal initial albumin, high Ki-67, and germinal center histology favored better survival.

Magnesium microspheres to enhance lipiodol-mediated transarterial chemo-embolization (TACE) of hepatocellular carcinoma: From bench to a pilot clinical study.

e16204 Background: Transarterial chemoembolization (TACE) has been extensively used in clinic to treat unresectable hepatocellular carcinoma (HCC). However, arterial embolization would worsen the hostile physicochemical features in the tumor microenvironment (TME) by further reducing its pH and increasing hypoxia, leading to immunosuppressive TME and drug resistance. Methods: Magnesium microspheres (Mg MSs), acting as H2 donors and pH modulators, were prepared via gas atomization pulverization. Characterization included inverted optical microscopy, SEM, and XRD analysis. Their H2 generation and acid neutralization capabilities were confirmed. The Lip-Mg dispersion (Mg MSs dispersed in lipiodol) was tested for therapeutic efficacy in H22 murine liver tumor-bearing mice, 4T1, and CT26 subcutaneous tumor models, as well as in vivo interventional TAE therapy for rabbit orthotopic liver tumors. The modulated capacities of Lip-Mg in H2 gas generation, acid neutralization, and promotion of antitumor immune response were investigated in vivo. Finally, a single-center, single-arm, open-label trial (ChiCTR2200064999) evaluated the safety and efficacy of TACE treatment with Lip-Mg (M-TACE) in Chinese HCC patients. Results: Inverted optical microscopy and SEM images confirmed uniform, smooth Mg microspheres (~60 μm) with a grayish-white color. In acidic buffer (pH 6.4), Mg microspheres rapidly increased pH, as measured by pH meter or fluorescent probe. Lip-Mg treatment significantly inhibited tumor growth compared to controls, prolonging mouse survival by ~2-fold, validated in 4T1 and CT26 models. Ultrasonic and multispectral fluorescence imaging demonstrated Lip-Mg's ability to release H2 and neutralize pH in vivo, reversing the immunosuppressive tumor microenvironment. Clinical study showed manageable treatment-related adverse events, with no unexpected toxicities and negligible impact on serum magnesium levels, confirming the safety of Mg microspheres for M-TACE. According to mRECIST, M-TACE exhibited high CR (61.5%), PR (38.5%), and ORR (100%) rates, with an overall response rate and CR rate of 90% and 60%, respectively. Conclusions: Metallic Mg microspheres (~60 μm) were developed to enhance lipiodol-mediated TAE/TACE for HCC. When combined with lipiodol and injected, they neutralized the acidic TME, triggered hydrogen therapy, and reversed immunosuppression, effectively inhibiting tumor growth. Lip-Mg showed superior outcomes to lipiodol alone for TAE therapy, with M-TACE treatment exhibiting higher ORR and CR rates than cTACE. Post-M-TACE, adverse events were managed well without treatment discontinuations. Our study introduces Mg microspheres as a promising embolic device for M-TACE therapy, potentially improving TACE benefits. Clinical trial information: ChiCTR2100050327.

Evaluating CR as a surrogate endpoint for PFS in R/R chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL): A meta-analysis of randomized controlled trials (RCT).

7046 Background: CLL/SLL is the most common leukemia in adults. Achieving a CR by International Workshop on CLL 2018 criteria indicates complete eradication of CLL/SLL in all disease compartments. Patients with R/R CLL/SLL who achieved CR tend to have delayed disease progression/death compared with patients who did not achieve CR. This is the first report to evaluate CR as a surrogate endpoint for PFS in R/R CLL/SLL using aggregate RCT data. Methods: A systematic literature review (SLR) identified published RCTs in R/R CLL/SLL from inception to 10/2023, reporting nonzero CR rates (CRR) and PFS. Association between treatment effects on CR and PFS across RCTs was estimated using a weighted linear model (WLM) in the primary analysis, and Daniels and Hughes (D&amp;H) and Riley bivariate random-effects meta-analysis (BRMA) in sensitivity analyses. Strength of association was assessed based on surrogacy criteria described by D&amp;H. Predictive performance of models was evaluated using leave-one-out cross-validation. Results: The SLR identified 13 RCTs with a total of 4388 patients with R/R CLL/SLL treated with a variety of therapies, including but not limited to BTKi, BCL2i, PI3Ki, CAR T cell therapy, anti-CD20 mAb, and chemotherapy. Across the evidence base, CRR ranged from 0.48% to 38.10% and median PFS was between 1 and 35.9 months (excluding unreached medians). Across RCTs, contrasting treatment and control arms, higher odds of CR resulted in lower hazards of disease progression/death (CRR improvement translated to PFS benefit). D&amp;H surrogacy criteria were met for WLM: 1) a near-zero, statistically nonsignificant intercept, indicating that no treatment effect on CRR implies no effect on PFS; 2) a negative, statistically significant slope, suggesting that improved CRR correlates with longer PFS; and 3) a near-zero conditional variance, meaning that PFS HR variation was primarily explained by CR odds ratio. During cross-validation, treatment effects on CR were predictive of PFS benefits, as the 95% predictive interval of PFS HR contained the observed HR in all RCTs for WLM. Results were largely consistent across all 3 models(Table). Conclusions: Improved CRR corresponds to prolonged PFS across RCTs and treatment comparisons. The results support CRR as an important treatment goal for R/R CLL/SLL and a valid surrogate endpoint. Consistent results and predictive performance across different models indicate the robustness of the results. [Table: see text]

Carfilzomib plus rituximab, ifosfamide, carboplatin and etoposide (C-RICE) led to higher response, OS, and PFS in patients with transplant-eligible relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL).

7042 Background: The CORAL study highlighted the need to develop novel salvage regimens for R/Rr/r DLBCL previously treated with R+CHOP. Overall response rate (ORR) to second line immuno-chemotherapy was 51% with a 3-year progression free survival (PFS) of 30% following high-dose chemotherapy and autologous stem cell support (HDC-ASCS). Optimal disease control (complete remission [CR] or partial remission [PR]) prior to HDC-ADCS and more recently to chimeric antigen receptor T-cell therapy (CAR T), correlates with improved outcomes. Dysregulation of Bcl-2 family members has been associated with acquired resistance to rituximab and chemotherapy which we have previously shown may be mitigated by co-treatment with proteasome inhibition in pre-clinical model. Subsequently, we conducted a Phase I/II clinical trial evaluating the safety and efficacy of CRICE as salvage therapy for R/R DLBCL (Blood Adv. 2023 7:1146-1155). Methods: Here we retrospectively compared the clinical outcomes of R/R DLBCL patients treated with CRICE (N=28) versus RICE (N=38) on our prior clinical trial (NCT01959698). Demographic, clinical, and pathological characteristics were collected for both groups (Table). Study endpoints consisted of differences in overall response rate (ORR), CR/PR rates, median progression free survival (PFS) and overall survival (OS) between the two cohorts. Results: The addition of Carfilzomib to RICE resulted in improved clinical outcomes. A higher ORR (92.9 vs 76.3, P=0.073) and CR rates (82.1 vs. 44.7, P=0.002) were observed in CRICE vs. RICE treated patients. Multivariate analysis confirmed the higher CR rates in CRICE vs. RICE when adjusted by DLBCL subtype (GCB vs. nNon-GCB, P=0.003). More CRICE patients proceeded to HDC-ASCS (52.6% vs. 47.4%, P=0.618). The 3yr PFS rate was higher in CRICE (54%, 32-72%) vs. RICE treated patients (35%, 19-51%). While the median PFS was longer in CRICE treated patients 36.8m (0.8, 73.2) vs. 3.2m (0.5, 54.2) (RICE), it did not reach statistical significance (P=0.714). No differences in OS were observed between CRICE &amp; RICE patients, median OS 67.3m vs. 71.8m. Conclusions: The CRICE outcomes were more striking in patients with non-GCB r/r DLBCL (ORR 85%, mPFS and OS not reached). CRICE led to high CR rates and longer PFS among r/r DLBCL patients, especially in non-GCB DLBCL patients. CRICE could be an attractive regimen to achieve disease control in r/r DLBCL patients undergoing consolidation therapy with HDC-ASCT or CAR T-cell therapy. [Table: see text]

PEMDA-HN, an open-label, phase II, randomized controlled study of danvatirsen plus pembrolizumab compared to pembrolizumab alone in first-line recurrent and/or metastatic head and neck squamous cell carcinoma (RM HNSCC).

TPS6113 Background: Signal transducer and activator of transcription 3 (STAT3) plays critical roles in promotion of an immune-suppressive tumor microenvironment and survival of tumor cells. Danvatirsen (DANVA) is a 16-nucleotide, generation 2.5 antisense oligonucleotide designed to down-regulate the expression of human STAT3 mRNA. Over 500 patients with hematologic malignancies or solid tumors have been exposed to DANVA monotherapy or in combination. A tolerable safety profile has been demonstrated for DANVA and toxicities are manageable. The SCORES study in recurrent and/or metastatic (RM) HNSCC patients, naïve to programmed cell death (ligand)1 (PD-(L)1) therapy, demonstrated that DANVA in combination with the PD-L1 inhibitory antibody durvalumab administered in the second line setting appeared to result in a higher objective response rate (ORR) (22.6% [12.3-36.2]) compared with the ORRs seen with durvalumab alone in prior studies (Cohen E. et al. Ann. Oncol., 2018). Several patients had complete responses (CR, 9.4%). The ORR was higher in patients with a PD-L1 tumor proportion score (TPS) ≥1 and ≥20, with increasing benefit noted with higher PD-L1 expression compared with historic anti-PD-(L)1 monotherapy data. The current study aims at evaluating the first-line combination of DANVA with pembrolizumab, an anti-PD-1 agent approved as first-line monotherapy for RM HNSCC in patients with PD-L1 positive disease. Methods: PEMDA-HN is a multicenter, open-label, randomized phase 2 study utilizing a Bayesian Optimal design (BOP2). Approximatively 81 RM HNSCC patients with a PD-L1 combined positive score (CPS) score ≥1 will be randomized in a 2:1 ratio stratified based on CPS&lt;20 and CPS≥20 to receive either DANVA (3 mg/kg IV Days 1, 3, and 5 and then weekly starting on Day 8) and pembrolizumab (200 mg IV every 3 weeks) or pembrolizumab alone as a first line therapy for recurrent or metastatic disease. Eligible patients will receive study treatment until disease progression or discontinuation. The primary endpoint of the study is ORR by response evaluation criteria in solid tumors version 1.1 (RECIST 1.1) as assessed by the investigator. Key secondary objectives are safety, additional antitumor activity evaluation (CR rate, duration of response, disease control rate, progression-free and overall survival) and pharmacokinetics. Efficacy (e.g. ORR, CR rate) will be evaluated in all patients and in subsets of patients with CPS&lt;20, CPS≥20 and CPS≥50. Exploratory endpoints include but are not limited to target engagement and biomarker evaluation. The study is being, or will be, conducted at US, South Korea and United-Kingdom study centers. Clinical trial information: NCT05814666 .

Real-world outcomes of lisocabtagene maraleucel (liso-cel) in patients (pt) with Richter transformation (RT) from the Center for International Blood and Marrow Transplant Research (CIBMTR).

7010 Background: Pts with RT have poor prognosis and no standard treatment options with median OS of 3–12 mo (Eyre TA. Hematology Am Soc Hematol Educ Program 2023), indicating an unmet need. We report the largest cohort of real-world pts with RT treated with commercial liso-cel, an autologous, CD19-directed, 4-1BB CAR T cell product. Methods: This analysis included US pts with RT from the CIBMTR who received commercial liso-cel between 02/2021 and 02/2023. Primary outcomes included ORR, CR rate, duration of response (DOR), PFS, OS, and safety (including cytokine release syndrome [CRS] and immune effector cell-associated neurotoxicity syndrome [ICANS] based on Lee 2018 criteria, and prolonged cytopenia defined as grade [gr] 4 thrombocytopenia and/or neutropenia persistent at 30 d after infusion). Results: At data cutoff (08/04/2023), 30 pts with RT were included. Demographics and baseline characteristics at liso-cel infusion are shown in the Table; additional data regarding the pts’ indolent disease and treatment history will be provided in the presentation. Median time from leukapheresis to liso-cel infusion was 35 d (range, 28–63). At median follow-up of 12.3 mo, ORR was 76% among evaluable pts (n = 29) with 66% in CR. Median time to first response was 1.1 mo (range, 0–3.1). Median DOR was not reached (NR); 12-mo DOR rate was 77% (95% CI, 49.5–91). Median PFS (n = 29) and median OS (n = 30) were NR; estimated 12-mo PFS was 54% (95% CI, 33–72) and 12-mo OS was 67% (95% CI, 44–83). Overall, 70% of pts had CRS (gr 3, 0; gr 4, 3%; gr 5, 3% [this pt also had hemophagocytic lymphohistiocytosis]); most common CRS treatments were corticosteroids and tocilizumab (23%) and tocilizumab (20%). ICANS was seen in 47% of pts (gr 3, 17%; gr 4, 10%; gr 5, 0) and most commonly treated with corticosteroids (23%), antiepileptics and corticosteroids (7%), and antiepileptics (7%). Prolonged cytopenia occurred in 17% of pts. One pt had a second primary malignancy (gastrointestinal). Eight (27%) pts died, including 7 because of progression. Conclusions: Pts with RT have poor prognosis with a high unmet need. Here, we show that liso-cel provided meaningful clinical benefit with low incidences of gr ≥ 3 CRS and ICANS observed. The high CR rate is promising in this difficult-to-treat population, and longer follow-up in a larger cohort is needed. [Table: see text]

Characteristics and outcomes of plasmablastic lymphoma in a predominantly Hispanic population.

e19079 Background: Plasmablastic lymphoma (PBL) is a rare subtype of diffuse large B-cell lymphoma and is frequently associated with immunosuppression. PBL displays immunoblastic morphology and a plasma cell immunophenotype. Data regarding patient characteristics, outcomes, and optimal treatment for this disease is limited. The reported prognosis of patients with PBL has been historically poor, with median overall survival ranging from 6 to 18 months. A recent publication of the SEER/NCDB database found a significantly improved OS in the Hispanic population (HR 0.7, p=0.014). This study investigates demographic, treatment, and survival outcomes for a primarily Hispanic PBL population. Methods: We identified 42 cases of pathologically confirmed PBL at two high volume tertiary care centers in Southern California between March 2010 and June 2023. Chart review was used to collect data on clinical presentation, treatment, and outcomes. Results: Median age of patients at diagnosis was 46 years (range 17-91 years) and 90% were male. Hispanic patients represented 81% of the total cohort. Predisposing immunosuppression was identified in 60%, and 50% of the total cohort were HIV-positive. Pathologic analysis showed EBV positivity by EBER in situ hybridization in 67%. 76% of patients presented with advanced disease (Stage III/IV). The most common regimens were EPOCH (27%) and V-EPOCH (49%). Response rates and CR rates were 63% and 50% respectively. Median follow-up was 10.5 months. OS was 72% at 1-year and 60% at 2-years. Conclusions: Our cohort demonstrated a 1-year OS of 72% compared to the 56% 1-year OS for PBLs in the SEER/NCDB database. There was no statistically significant difference in survival between the Hispanic and Non-Hispanic cohorts in our study. However, this is likely due to the small sample size in the latter. Notably, our patient population had more advanced disease at presentation (76% Stage III/IV) than the SEER/NCDB cohort (60% Stage III/IV). This improved survival is likely multifactorial, but could represent ethnic differences in PBL biology, high EBV positivity, and the frequent utilization of higher intensity regimens (EPOCH/V-EPOCH = 76%). Further studies are needed to better characterize this disease in the Hispanic population. [Table: see text]