The enchanting canvas of CAR technology: Unveiling its wonders in non-neoplastic diseases.

Chimeric antigen receptor (CAR) T cells have made a groundbreaking advancement in personalized immunotherapy and achieved widespread success in hematological malignancies. As CAR technology continues to evolve, numerous studies have unveiled its potential far beyond the realm of oncology. This review focuses on the current applications of CAR-based cellular platforms in non-neoplastic indications, such as autoimmune, infectious, fibrotic, and cellular senescence-associated diseases. Furthermore, we delve into the utilization of CARs in non-T cell populations such as natural killer (NK) cells and macrophages, highlighting their therapeutic potential in non-neoplastic conditions and offering the potential for targeted, personalized therapies to improve patient outcomes and enhanced quality of life.

Oscillatory correlates of threat imminence during virtual navigation.

The Predatory Imminence Continuum Theory proposes that defensive behaviors depend on the proximity of a threat. While the neural mechanisms underlying this proposal are well studied in animal models, it remains poorly understood in humans. To address this issue, we recorded EEG from 24 (15 female) young adults engaged in a first-person virtual reality Risk-Reward interaction task. On each trial, participants were placed in a virtual room and presented with either a threat or reward conditioned stimulus (CS) in the same room location (proximal) or different room location (distal). Behaviorally, all participants learned to avoid the threat-CS, with most using the optimal behavior to actively avoid the proximal threat-CS (88% accuracy) and passively avoid the distal threat-CS (69% accuracy). Similarly, participants learned to actively approach the distal reward-CS (82% accuracy) and to remain passive to the proximal reward-CS (72% accuracy). At an electrophysiological level, we observed a general increase in theta power (4-8 Hz) over the right posterior channel P8 across all conditions, with the proximal threat-CS evoking the largest theta response. By contrast, distal cues induced two bursts of gamma (30-60 Hz) power over midline-parietal channel Pz (200 msec post-cue) and right frontal channel Fp2 (300 msec post-cue). Interestingly, the first burst of gamma power was sensitive to the distal threat-CS and the second burst at channel Fp2 was sensitive to the distal reward-CS. Together, these findings demonstrate that oscillatory processes differentiate between the spatial proximity information during threat and reward encoding, likely optimizing the selection of the appropriate behavioral response.

[18F]FDG PET/CT for prognosis and toxicity prediction of diffuse large B-cell lymphoma patients with chimeric antigen receptor T-cell therapy.

PURPOSE: Chimeric antigen receptor (CAR) T-cell therapy has been confirmed to benefit patients with relapsed and/or refractory diffuse large B-cell lymphoma (DLBCL). It is important to provide precise and timely predictions of the efficacy and toxicity of CAR T-cell therapy. In this study, we evaluated the value of [18F]fluorodeoxyglucose positron emission tomography/computed tomography ([18F]FDG PET/CT) combining with clinical indices and laboratory indicators in predicting outcomes and toxicity of anti-CD19 CAR T-cell therapy for DLBCL patients. METHODS: Thirty-eight DLBCL patients who received CAR T-cell therapy and underwent [18F]FDG PET/CT within 3 months before (pre-infusion) and 1 month after CAR T-cell infusion (M1) were retrospectively reviewed and regularly followed up. Maximum standardized uptake value (SUVmax), total lesion glycolysis (TLG), metabolic tumor volume (MTV), clinical indices, and laboratory indicators were recorded at pre-infusion and M1 time points, and changes in these indices were calculated. Progression-free survival (PFS) and overall survival (OS) were as endpoints. Based on the multivariate Cox regression analysis, two predictive models for PFS and OS were developed and evaluated the efficiency. Pre-infusion indices were subjected to predict the grade of cytokine release syndrome (CRS) resulting from toxic reactions. RESULTS: For survival analysis at a median follow-up time of 18.2 months, patients with values of international prognostic index (IPI), SUVmax at M1, and TLG at M1 above their optimal thresholds had a shorter PFS (median PFS: 8.1 months [IPI ≥ 2] vs. 26.2 months [IPI < 2], P = 0.025; 3.1 months [SUVmax ≥ 5.69] vs. 26.8 months [SUVmax < 5.69], P < 0.001; and 3.1 months [TLG ≥ 23.79] vs. 26.8 months [TLG < 23.79], P < 0.001). In addition, patients with values of SUVmax at M1 and ∆SUVmax% above their optimal thresholds had a shorter OS (median OS: 12.6 months [SUVmax ≥ 15.93] vs. 'not reached' [SUVmax < 15.93], P < 0.001; 32.5 months [∆SUVmax% ≥ -46.76] vs. 'not reached' [∆SUVmax% < -46.76], P = 0.012). Two novel predictive models for PFS and OS were visualized using nomogram. The calibration analysis and the decision curves demonstrated good performance of the models. Spearman's rank correlation (rs) analysis revealed that the CRS grade correlated strongly with the pre-infusion SUVmax (rs = 0.806, P < 0.001) and moderately with the pre-infusion TLG (rs = 0.534, P < 0.001). Multinomial logistic regression analysis revealed that the pre-infusion value of SUVmax correlated with the risk of developing a higher grade of CRS (P < 0.001). CONCLUSION: In this group of DLBCL patients who underwent CAR T-cell therapy, SUVmax at M1, TLG at M1, and IPI were independent risk factors for PFS, and SUVmax at M1 and ∆SUVmax% for OS. Based on these indicators, two novel predictive models were established and verified the efficiency for evaluating PFS and OS. Moreover, pre-infusion SUVmax correlated with the severity of any subsequent CRS. We conclude that metabolic parameters measured using [18F]FDG PET/CT can identify DLBCL patients who will benefit most from CAR T-cell therapy, and the value before CAR T-cell infusion may predict its toxicity in advance.

The evolution of preexisting primary immune thrombocytopenia after COVID-19 onset: A nationally representative, prospective, multicentre, observational study.

The symptoms in patients with primary immune thrombocytopenia (ITP) after COVID-19 onset remain largely unclear. The aim of this study was to describe the platelet count fluctuations in ITP patients following the diagnosis of COVID-19. A prospective multicentre observational study was conducted from December 15th, 2022, to January 31st, 2023 in 39 general hospitals across China. Patients with preexisting primary ITP who were newly diagnosed with COVID-19 were enrolled. A total of 1216 ITP patients with newly-diagnosed COVID-19 were enrolled. 375 (30.8%) patients experienced ITP exacerbation within eight weeks after the diagnosis of COVID-19, and most exacerbation (266/375, 70.9%) developed in the first two weeks. Immunosuppressive therapy for ITP and severe/critical COVID-19 infection were independent variables associated with ITP exacerbation. Overall the platelet count had a transient increasing trend, and the platelet peak value occurred at two weeks after COVID-19 infection. Then, the platelet count decreased to the baseline level in the following weeks. The platelet count had a transient increasing trend in ITP patients following the diagnosis of COVID-19. ITP exacerbation only occurred in less than one-third of ITP patients. Nonimmunosuppressive therapy may have an advantage to prevent ITP exacerbation during COVID-19.

GPIbα CAAR-T cells function like a Trojan horse to eliminate autoreactive B cells to treat immune thrombocytopenia.

Breakthrough treatment for refractory and relapsed immune thrombocytopenia (ITP) patients is urgently needed. Autoantibody-mediated platelet clearance and megakaryocyte dysfunction are important pathogenic mediators of ITP. Glycoprotein (GP) Ibα is a significant autoantigen found in ITP patients and is associated with poor response to standard immunosuppressive treatments. Here, we engineered human T cells to express a chimeric autoantibody receptor (CAAR) with GPIbα constructed into the ligand-binding domain fused to the CD8 transmembrane domain and CD3ζ-4-1BB signaling domains. We performed cytotoxicity assays to assess GPIbα CAAR-T-cell selective cytolysis of cells expressing anti-GPIbα B-cell receptors (BCRs) in vitro. Furthermore, we demonstrated the potential of GPIbα CAAR-T cells to persist and precisely eliminate GPIbα-specific B cells in vivo. In summary, we present a proof of concept for CAAR-T-cell therapy to eradicate autoimmune B cells while sparing healthy B cells with GPIbα CAAR-T cells that function like a Trojan horse. GPIbα CAAR-Tcell therapy is a promising treatment for refractory and relapsed ITP patients.

Targeting autophagy overcomes cancer-intrinsic resistance to CAR-T immunotherapy in B-cell malignancies.

BACKGROUND: Chimeric antigen receptor T (CAR-T) therapy has substantially revolutionized the clinical outcomes of patients with hematologic malignancies, but the cancer-intrinsic mechanisms underlying resistance to CAR-T cells remain yet to be fully understood. This study aims to explore the molecular determinants of cancer cell sensitivity to CAR-T cell-mediated killing and to provide a better understanding of the underlying mechanisms and potential modulation to improve clinical efficacy. METHODS: The human whole-genome CRISPR/Cas9-based knockout screening was conducted to identify key genes that enable cancer cells to evade CD19 CAR-T-cell-mediated killing. The in vitro cytotoxicity assays and evaluation of tumor tissue and bone marrow specimens were further conducted to confirm the role of the key genes in cancer cell susceptibility to CAR-T cells. In addition, the specific mechanisms influencing CAR-T cell-mediated cancer clearance were elucidated in mouse and cellular models. RESULTS: The CRISPR/Cas9-based knockout screening showed that the enrichment of autophagy-related genes (ATG3, BECN1, and RB1CC1) provided protection of cancer cells from CD19 CAR-T cell-mediated cytotoxicity. These findings were further validated by in vitro cytotoxicity assays in cells with genetic and pharmacological inhibition of autophagy. Notably, higher expression of the three autophagy-related proteins in tumor samples was correlated with poorer responsiveness and worse survival in patients with relapsed/refractory B-cell lymphoma after CD19 CAR-T therapy. Bulk RNA sequencing analysis of bone marrow samples from B-cell leukemia patients also suggested the clinical relevance of autophagy to the therapeutic response and relapse after CD19 CAR-T cell therapy. Pharmacological inhibition of autophagy and knockout of RB1CC1 could dramatically sensitize tumor cells to CD19 CAR-T cell-mediated killing in mouse models of both B-cell leukemia and lymphoma. Moreover, our study revealed that cancer-intrinsic autophagy mediates evasion of CAR-T cells via the TNF-α-TNFR1 axis-mediated apoptosis and STAT1/IRF1-induced chemokine signaling activation. CONCLUSIONS: These findings confirm that autophagy signaling in B-cell malignancies is essential for the effective cytotoxic function of CAR-T cells and thereby pave the way for the development of autophagy-targeting strategies to improve the clinical efficacy of CAR-T cell immunotherapy.

Harnessing Biomaterials for Safeguarding Chimeric Antigen Receptor T Cell Therapy: An Artful Expedition in Mitigating Adverse Effects.

Chimeric antigen receptor T cell (CAR-T) therapy has emerged as a groundbreaking approach in cancer treatment, showcasing remarkable efficacy. However, the formidable challenge lies in taming the formidable side effects associated with this innovative therapy, among which cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS) and on-target off-tumor toxicities (OTOT) are typical representatives. Championing the next frontier in cellular immunotherapy, this comprehensive review embarks on an artistic exploration of leveraging biomaterials to meticulously navigate the intricate landscape of CAR-T cell therapy. Unraveling the tapestry of potential toxicities, our discourse unveils a symphony of innovative strategies designed to elevate the safety profile of this revolutionary therapeutic approach. Through the lens of advanced medical science, we illuminate the promise of biomaterial interventions in sculpting a safer and more efficacious path for CAR-T cell therapy, transcending the boundaries of conventional treatment paradigms.

Bispecific CS1-BCMA CAR-T cells are clinically active in relapsed or refractory multiple myeloma.

Multiple myeloma (MM) bears heterogeneous cells that poses a challenge for single-target immunotherapies. Here we constructed bispecific CS1-BCMA CAR-T cells aiming to augment BCMA targeting with CS1. Sixteen patients with relapsed or refractory (RR) MM received CS1-BCMA CAR-T infusion. Six patients (38%) had cytokine release syndrome, which was of grade 1-2 in 31%. No neurological toxicities were observed. The most common severe adverse events were hematological, including leukopenia (100%), neutropenia (94%), lymphopenia (100%) and thrombocytopenia (31%). Three patients with solitary extramedullary disease (sEMD) did not respond. At a median follow-up of 246 days, 13 patients (81%) had an overall response and attained minimal residual disease-negativity, and six (38%) reached a stringent complete response (sCR). Among the 13 responders, 1-year overall survival and progression-free survival were 72.73% and 56.26%, respectively. Four patients maintained sCR with a median duration of 17 months. Four patients experienced BCMA+ and CS1+ relapse or progression. One patient responded after anti-BCMA CAR-T treatment failure. Lenalidomide maintenance after CAR-T infusion and the resistance mechanism of sEMD were preliminarily explored in three patients. CAR-T cells persisted at a median of 406 days. Soluble BCMA could serve as an ideal biomarker for efficacy monitoring. CS1-BCMA CAR-T cells were clinically active with good safety profiles in patients with RRMM. Clinical trial registration: This study was registered on ClinicalTrials.gov, number NCT04662099.

Insights gained from single-cell analysis of chimeric antigen receptor T-cell immunotherapy in cancer.

Advances in chimeric antigen receptor (CAR)-T cell therapy have significantly improved clinical outcomes of patients with relapsed or refractory hematologic malignancies. However, progress is still hindered as clinical benefit is only available for a fraction of patients. A lack of understanding of CAR-T cell behaviors in vivo at the single-cell level impedes their more extensive application in clinical practice. Mounting evidence suggests that single-cell sequencing techniques can help perfect the receptor design, guide gene-based T cell modification, and optimize the CAR-T manufacturing conditions, and all of them are essential for long-term immunosurveillance and more favorable clinical outcomes. The information generated by employing these methods also potentially informs our understanding of the numerous complex factors that dictate therapeutic efficacy and toxicities. In this review, we discuss the reasons why CAR-T immunotherapy fails in clinical practice and what this field has learned since the milestone of single-cell sequencing technologies. We further outline recent advances in the application of single-cell analyses in CAR-T immunotherapy. Specifically, we provide an overview of single-cell studies focusing on target antigens, CAR-transgene integration, and preclinical research and clinical applications, and then discuss how it will affect the future of CAR-T cell therapy.

Efficacy and safety of Orelabrutinib-based regimens in diffuse large B-cell lymphoma: a single-center retrospective analysis.

Currently, combining chemotherapy with Bruton tyrosine kinase inhibitors (BTKi) has demonstrated significant effectiveness in treating patients with diffuse large B-cell lymphoma. Orelabrutinib is a second-generation BTK inhibitor, and presently, there have been few reports of Orelabrutinib being used to treat DLBCL. We conducted a retrospective investigation to explore the safety and efficacy of Orelabrutinib in combination with chemotherapy or immunotherapy. The study comprised 19 patients with a median age of 61 years. The overall response rate (ORR) was 89.5% with a complete response (CR) rate of 73.7% and a partial response rate (PR) of 15.8%. The estimated 2-year overall survival (OS) and progression-free survival (PFS) rates were 78.6% (95%CI, 59.8%-100%) and 72.2% (95% CI, 52.4%-99.6%), respectively, with a median follow-up time of 11 months (range 2-24). The most prevalent grade 3 or 4 adverse events (AEs), neutropenia (52.6%), anemia (36.8%), thrombocytopenia (26.3%), febrile neutropenia (26.3%), and lung infection (10.5%), were the most common. Our results reveal that Orelabrutinib is an effective therapy for DLBCL patients. Furthermore, our first investigation of the Orelabrutinib application lays a foundation for larger retrospective studies.

The diagnostic value of dual-layer CT in the assessment of lymph nodes in lymphoma patients with PET/CT as a reference standard.

This study aimed to evaluate the diagnostic performances of dual-layer CT (DLCT) for the identification of positive lymph nodes (LNs) in patients with lymphoma and retrospectively included 1165 LNs obtained by biopsy from 78 patients with histologically proven lymphoma, who underwent both pretreatment DLCT and 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT). According to 18F-FDG PET/CT findings as a reference standard, cases were categorized into the LN-negative and LN-positive groups. LNs were then randomly divided at a ratio of 7:3 into the training (n = 809) and validation (n = 356) cohorts. The patients' clinical characteristics and quantitative parameters including spectral curve slope (λHU), iodine concentration (IC) on arterial phase (AP) and venous phase (VP) images were compared between the LN-negative and LN-positive groups using Chi-square test, t-test or Mann-Whitney U test for categorical variables or quantitative parameters. Multivariate logistic regression analysis with tenfold cross-validation was performed to establish the most efficient predictive model in the training cohort. The area under the curve (AUC) was used to evaluate the diagnostic value of the predictive model, and differences in AUC were determined by the DeLong test. Moreover, the predictive model was validated in the validation cohort. Repeatability analysis was performed for LNs using intraclass correlation coefficients (ICCs). In the training cohort, long diameter (LD) had the highest AUC as an independent factors compared to other parameter in differentiating LN positivity from LN negativity (p = 0.006 to p < 0.001), and the AUC of predictive model jointly involving LD and λHU-AP was significantly elevated (AUC of 0.816, p < 0.001). While the AUC of predictive model in the validation cohort was 0.786. Good to excellent repeatability was observed for all parameters (ICC > 0.75). The combination of DLCT with morphological and functional parameters may represent a potential imaging biomarker for detecting LN positivity in lymphoma.

Enhancing the Treatment of Uncontrolled Inflammation through the Targeted Delivery of TPCA-1-Loaded Nanoparticles.

Uncontrolled inflammation is a pathological state that underlies many diseases. Despite the development of numerous anti-inflammatory agents, the treatment of uncontrolled inflammation remains a challenging task. We developed a targeted delivery system for [5-(p-fluorophenyl)-2-ureido]thiophene-3-carboxamide (TPCA-1), a potent inhibitor of the NF-κB signaling pathway. The system comprises TPCA-1-loaded nanoparticles (NPs) functionalized with a monoclonal antibody (mAb) that specifically binds to the break point of the IgD6 region of the platelet/endothelial cell adhesion molecule-1 (PECAM-1) extracellular segment that is overexposed on the injured endothelium and activated macrophages during the pathogenesis of inflammation. In vitro binding and cellular uptake experiments revealed that the mAb modification on NPs could significantly enhance uptake by both Raw264.7 and HUVEC compared with unmodified NPs. In studies conducted at the cellular level focusing on anti-inflammatory and antioxidant effects, this formulation was found to effectively inhibit M1 polarization of macrophages, downregulate the secretion of pro-inflammatory cytokines, and reduce the production of reactive oxygen species (ROS) and nitric oxide (NO). In an animal model of vascular endothelial injury with acute inflammation, these NPs were capable of delivering TPCA-1 to inflammatory lesions in a targeted manner. Compared with the free agent-treated group, the NP-treated group exhibited reduced infiltration of inflammatory cells. In conclusion, our study demonstrates that this targeted delivery of TPCA-1-loaded NPs represents a promising strategy for improved mitigation of uncontrolled inflammation.

Advances in CAR-Engineered Immune Cell Generation: Engineering Approaches and Sourcing Strategies.

Chimeric antigen receptor T-cell (CAR-T) therapy has emerged as a highly efficacious treatment modality for refractory and relapsed hematopoietic malignancies in recent years. Furthermore, CAR technologies for cancer immunotherapy have expanded from CAR-T to CAR-natural killer cell (CAR-NK), CAR-cytokine-induced killer cell (CAR-CIK), and CAR-macrophage (CAR-MΦ) therapy. Nevertheless, the high cost and complex manufacturing processes of ex vivo generation of autologous CAR products have hampered broader application. There is an urgent need to develop an efficient and economical paradigm shift for exploring new sourcing strategies and engineering approaches toward generating CAR-engineered immune cells to benefit cancer patients. Currently, researchers are actively investigating various strategies to optimize the preparation and sourcing of these potent immunotherapeutic agents. In this work, the latest research progress is summarized. Perspectives on the future of CAR-engineered immune cell manufacturing are provided, and the engineering approaches, and diverse sources used for their development are focused upon.

IL-10 plus the EASIX score predict bleeding events after anti-CD19 CAR T-cell therapy.

Chimeric antigen receptor (CAR) T-cell-associated coagulopathy can cause bleeding events. To explore risk factors for hemorrhage after CAR T-cell therapy, we retrospectively analyzed routine indicators in 56 patients with non-Hodgkin lymphoma and B-cell acute lymphoblastic leukemia who received anti-CD19 CAR T-cell therapy. Disturbance of coagulation occurred mainly within one month post infusion, especially on day 7 and 14. The cumulative incidence of bleeding events within one month was 32.8%, with the median onset of 7 (range, 0-28) days. All bleeding events were grade 1-3. Patients who experienced bleeding events within one month had longer prothrombin time, higher IL-6, higher IL-10, and lower platelets before lymphodepletion. There were also correlations among coagulation-, inflammatory-, and tumor burden-related markers. Multi-variate analysis showed IL-10 (> 7.98 pg/mL; adjusted odds ratio [OR], 13.84; 95% confidence interval [CI], 2.03-94.36; P = 0.007) and the endothelial activation and stress index (EASIX, defined as dehydrogenase [U/L] × creatinine [mg/dL] / platelets [×109 cells/L]; >7.65; adjusted OR, 7.06; 95% CI, 1.03-48.23; P = 0.046) were significant risk factors for bleeding events. IL-10 plus the EASIX defined three risk groups for bleeding events with cumulative incidence of 100% (hazard ratio [HR], 14.47; 95% CI, 2.78-75.29; P < 0.0001), 38.5% (HR, 3.68; 95% CI, 0.82-16.67; P = 0.089), and 11.8% (reference), respectively. Future studies are needed to verify the risk assessment models for bleeding events after CAR T-cell treatment in larger cohorts.

Targeting CD22 for B-cell hematologic malignancies.

CD19-targeted chimeric receptor antigen (CAR)-T cell therapy has shown remarkable clinical efficacy in the treatment of relapsed or refractory (R/R) B-cell malignancies. However, 30%-60% of patients eventually relapsed, with the CD19-negative relapse being an important hurdle to sustained remission. CD22 expression is independent of CD19 expression in malignant B cells. Consequently, CD22 is a potential alternative target for CD19 CAR-T cell-resistant patients. CD22-targeted therapies, mainly including the antibody-drug conjugates (ADCs) and CAR-T cells, have come into wide clinical use with acceptable toxicities and promising efficacy. In this review, we explore the molecular and physiological characteristics of CD22, development of CD22 ADCs and CAR-T cells, and the available clinical data on CD22 ADCs and CAR-T cell therapies. Furthermore, we propose some perspectives for overcoming tumor escape and enhancing the efficacy of CD22-targeted therapies.

Dynamical modelling of viral infection and cooperative immune protection in COVID-19 patients.

Once challenged by the SARS-CoV-2 virus, the human host immune system triggers a dynamic process against infection. We constructed a mathematical model to describe host innate and adaptive immune response to viral challenge. Based on the dynamic properties of viral load and immune response, we classified the resulting dynamics into four modes, reflecting increasing severity of COVID-19 disease. We found the numerical product of immune system's ability to clear the virus and to kill the infected cells, namely immune efficacy, to be predictive of disease severity. We also investigated vaccine-induced protection against SARS-CoV-2 infection. Results suggested that immune efficacy based on memory T cells and neutralizing antibody titers could be used to predict population vaccine protection rates. Finally, we analyzed infection dynamics of SARS-CoV-2 variants within the construct of our mathematical model. Overall, our results provide a systematic framework for understanding the dynamics of host response upon challenge by SARS-CoV-2 infection, and this framework can be used to predict vaccine protection and perform clinical diagnosis.

Avatrombopag for adult chronic primary immune thrombocytopenia: a randomized phase 3 trial in China.

Background: Immune thrombocytopenia (ITP) is an autoimmune disorder with decreased platelet counts and increased bleeding risk. Objectives: To evaluate the efficacy and safety of avatrombopag, a second-generation oral thrombopoietin receptor agonist, for the treatment of Chinese patients with chronic primary ITP. Methods: This multicenter, randomized, double-blind, placebo-controlled phase 3 study (CTR20210431) consisted of a 6-week double-blind core treatment phase followed by a 20-week, open-label extension phase. Chinese adults with chronic primary ITP for at least 12 months and a platelet count <30 × 109/L were randomized (2:1) to receive avatrombopag (initial dose of 20 mg/day) or matched placebo. The primary endpoint was the proportion of subjects with a platelet count ≥50 × 109/L at week 6 of the core treatment phase in absence of rescue therapy. Results: In total, 74 patients were randomized (avatrombopag: N = 48; placebo: N = 26) between March 5, 2021, and August 6, 2021; all of whom entered the extension phase (72 received avatrombopag up to 26 weeks). At week 6 of the core study, the platelet response (≥50 x 109/L) rate was significantly higher in the avatrombopag group (77.1%; 95% CI, 62.7, 88.0) vs placebo (7.7%; 95% CI, 1.0, 25.1); the treatment difference was 69.4% (95% CI, 56.2, 86.3; P < .0001). During the 6-week core study, treatment-emergent adverse events were reported in 41 (85.4%) and 20 (76.9%) patients in the avatrombopag and placebo groups, respectively. The most common avatrombopag-related treatment-emergent adverse events were upper respiratory tract infection (14/48 [29.2%]), increased platelet count (13/48 [27.1%]) and headache (7/48 [14.6%]). Conclusion: Avatrombopag was efficacious and generally well tolerated in Chinese patients with chronic primary ITP, with comparable efficacy and safety to previous reports in Western patients.