Publications by authors named "KeShu Zhou"

Background: Amulirafusp alfa (IMM0306) is a fusion protein of CD47 binding domain of signal-regulatory protein alpha (SIRPα) with CD20 monoclonal antibody on both heavy chains. This study aimed to evaluate the safety and preliminary efficacy of amulirafusp alfa in relapsed or refractory (r/r) B-cell non-Hodgkin lymphoma (B-NHL).

Methods: We enrolled patients with CD20 + r/r B-NHL who had previously received at least two lines of therapy to receive a single-dose of amulirafusp alfa in the first 2 weeks, followed by a multiple-dose period, in which the patients received the same intravenous dose every week in 4-week cycles.

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Importance: Equecabtagene autoleucel (eque-cel), a fully human-derived B-cell maturation antigen-targeting chimeric antigen receptor (CAR) T-cell therapy, has exhibited potential for the treatment of relapsed or refractory multiple myeloma (RRMM), and further investigation in a larger cohort is necessary.

Objective: To evaluate whether eque-cel can benefit patients with RRMM and determine the overall response rate postinfusion.

Design, Setting, And Participants: The FUMANBA-1 trial was a single-arm, open-label, phase 1b/2 trial that evaluated eque-cel in adult patients with RRMM.

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Article Synopsis
  • CAR-T therapy has improved treatment options for relapsed/refractory B-cell lymphoblastic leukemia, but it can cause serious side effects like cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS).
  • A study involving 93 patients showed that while most (81.7%) experienced CRS and a few (5.3%) experienced ICANS, these conditions did not significantly impact treatment effectiveness or patient survival rates.
  • Ultimately, the findings suggest that experiencing CRS or ICANS does not lead to worse outcomes for patients receiving anti-CD19 CAR-T therapy.
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The ALPINE trial established the superiority of zanubrutinib over ibrutinib in patients with relapsed/refractory chronic lymphocytic leukemia and small lymphocytic lymphoma; here, we present data from the final comparative analysis with extended follow-up. Overall, 652 patients received zanubrutinib (n = 327) or ibrutinib (n = 325). At an overall median follow-up of 42.

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Purpose: Relapsed and/or refractory peripheral T-cell lymphoma (r/r PTCL) is an aggressive and heterogeneous hematologic malignancy with high unmet need. Previously, PI3K inhibitors were shown to be efficacious in B- and T-cell lymphomas, but as a drug class, these agents have frequently been observed to have tolerability limitations. Next-generation agents that improve the tolerability while maintaining efficacy are desirable.

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Acalabrutinib is a highly selective Bruton tyrosine kinase inhibitor approved in the United States and Europe for chronic lymphocytic leukemia (CLL) based on phase 3 trials with limited representation of Asian populations. This phase 1/2 trial evaluates acalabrutinib in Chinese adults with relapsed/refractory (R/R) CLL receiving acalabrutinib 100 mg twice daily in 28-day cycles until disease progression or treatment discontinuation due to adverse events (AEs) presenting substantial clinical risk. The primary endpoint was blinded independent central review (BICR)-assessed overall response rate (ORR).

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Article Synopsis
  • - Patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) typically have a poor prognosis, but Loncastuximab tesirine (Lonca), an antibody drug, has shown significant effectiveness in a global study (LOTIS-2).
  • - The China bridging pivotal phase 2 study treated eligible patients who had already undergone at least two previous treatments, showing an overall response rate of 51.6% and a complete response rate of 23.4% after a median of 4 cycles of treatment.
  • - While Lonca was generally well-tolerated, there were notable side effects, particularly in blood-related events, with serious treatment-emergent adverse events reported in 35 out
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Background: MIL62, a novel glycoengineered type Ⅱ anti-CD20 monoclonal antibody, with a nearly completely afucosylated N-glycans in Fc region, has demonstrated superior activity compared with rituximab and obinutuzumab in vitro and in vivo, respectively.

Methods: This multicentre, single-arm, phase 1b/2 trial aimed to explore the efficacy, pharmacokinetics, and safety of MIL62 combined with lenalidomide in patients with relapsed/refractory (R/R) follicular lymphoma (FL) or marginal zone lymphoma (MZL). Eligible patients included those who had histopathologically confirmed CD20 positive FL (grade 1-3a) or MZL and failed to be treated with rituximab.

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Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) has different epidemiology in Chinese vs. Western patients, but there are few studies of CLL/SLL in large populations of Chinese patients. ALPINE is a global phase 3 trial investigating Bruton tyrosine kinase inhibitors zanubrutinib vs.

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The lymphocyte-specific protein tyrosine kinase (LCK) plays a crucial role in both T-cell development and activation. Dysregulation of LCK signaling has been demonstrated to drive the oncogenesis of T-cell acute lymphoblastic leukemia (T-ALL), thus providing a therapeutic target for leukemia treatment. In this study, we introduced a sophisticated virtual screening strategy combined with biological evaluations to discover potent LCK inhibitors.

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Background: Tocilizumab is commonly used for the management of chimeric antigen receptor (CAR) T-cell therapy-associated cytokine release syndrome (CRS). However, it remains unknown whether tocilizumab or its dosage affects the efficacy and safety of CAR T-cell therapy. The objective of this multicenter retrospective study was to explore the impact of tocilizumab on CAR T-cell therapy.

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Acalabrutinib studies have limited Asian participation. This phase 1/2 study (NCT03932331) assessed acalabrutinib in Chinese patients with relapsed/refractory (R/R) mantle cell lymphoma (MCL). Primary endpoint was blinded independent central review (BICR)-assessed overall response rate (ORR).

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Over the past few years, dual-targeted chimeric antigen receptor (CAR) T-cell therapy has been employed in the management of hematological malignancies to mitigate treatment failure, particularly in cases of antigen escape. The most widely used approaches include CD19/CD20, CD20/CD22, and BCMA/CD19 CAR T-cells. Alternative immune cells, including natural killer T cells and invariant natural killer T cells, exhibit innate anti-tumor activity and reduced toxicity.

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Article Synopsis
  • - Sovleplenib (HMPL-523) is an experimental drug designed to target and inhibit spleen tyrosine kinase (Syk), showing potential effectiveness against B-cell cancers in early research.
  • - A Phase I clinical trial was conducted with 134 patients suffering from relapsed or refractory B-cell tumors, exploring different dosages of the drug (200-800 mg daily); the recommended phase II dose was established at 600 mg for heavier patients and 400 mg for lighter ones.
  • - The study found a 50.8% objective response rate in a subset of patients with indolent B-cell lymphoma, while some patients reported severe side effects, but overall, sovleplenib demonstrated promising anti-t
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Article Synopsis
  • * The study, which took place at 49 centers in Australia, China, South Korea, and the USA, included 104 patients who met eligibility criteria and received the medication at a daily dose of 150 mg until disease progression.
  • * Results showed that 88 patients were included in the primary analysis, with a median follow-up of 13.3 months, highlighting the drug's potential effectiveness in treating this challenging cancer type.
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Background: We previously reported results of a pooled analysis of two zanubrutinib studies in relapsed or refractory (R/R) MCL showing better survival outcomes when zanubrutinib is used in second-line versus later-line. Here, we present an updated pooled analysis with a longer follow-up of 35.2 months.

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The primary analysis of MAGNOLIA, an open-label, single-arm, multicenter, phase 2 study, demonstrated that the next-generation Bruton tyrosine kinase (BTK) inhibitor zanubrutinib provided a high overall response rate (ORR) in patients with relapsed/refractory marginal zone lymphoma (R/R MZL), with a favorable safety/tolerability profile. Presented here, is the final analysis of MAGNOLIA, performed to characterize the durability of response and longer-term safety and tolerability. Zanubrutinib (160 mg twice daily) was evaluated in 68 patients with R/R MZL who had received at least 1 anti-CD20-directed regimen.

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Article Synopsis
  • Marginal zone lymphoma (MZL) is a slow-growing non-Hodgkin lymphoma linked to abnormal B cell receptor signaling, and orelabrutinib is a new oral treatment evaluated for relapsed/refractory cases in a clinical study in China.
  • The study involved 111 patients, primarily with advanced MZL, and showed an overall response rate of 58.9% after a median follow-up of 24.3 months, with median duration of response lasting 34.3 months and an impressive 12-month progression-free survival rate of 82.8%.
  • While orelabrutinib was effective, some patients experienced treatment-related side effects, including anemia and infections, and 30.
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Adhesion molecules play essential roles in the homeostatic regulation and malignant transformation of hematopoietic cells. The dysregulated expression of adhesion molecules in leukemic cells accelerates disease progression and the development of drug resistance. Thus, targeting adhesion molecules represents an attractive anti-leukemic therapeutic strategy.

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Background: Hematopoietic stem cell transplantation (HSCT) is an important treatment for T-cell lymphoblastic lymphoma/leukemia (T-LBL). To compare the efficacy and influencing factors of autologous hematopoietic stem cell transplantation (auto-HSCT) with those of allogeneic hematopoietic stem cell transplantation (allo-HSCT) from different donors for the treatment of T-cell lymphoblastic lymphoma/leukemia (T-LBL) and provide a basis for selection of appropriate transplant methods and donors.

Methods: To provide evidence of appropriate transplant methods for these patients, we retrospectively summarized the clinical characteristics of 75 T-LBL patients receiving HSCT at Henan Cancer Hospital between March 2012 and October 2021.

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Diffuse large B cell lymphoma (DLBCL) is a type of cancer that originates from abnormal B cells in the lymph nodes or other lymphoid tissues. Dysfunction of deubiquitinases is frequently implicated in malignant progression. This study planned to uncover the biological roles of deubiquitinase USP25 during DLBCL tumorigenesis.

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We conducted two indirect comparisons to estimate the efficacy of zanubrutinib versus orelabrutinib in Chinese patients with relapsed or refractory (R/R) chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) or R/R mantle cell lymphoma (MCL). An unanchored matching-adjusted indirect comparison (MAIC) was performed in R/R CLL/SLL patients. Individual patient data from zanubrutinib trial (BGB-3111-205) were adjusted to match the aggregated data from the orelabrutinib trial (ICP-CL-00103).

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Article Synopsis
  • Relapsed or refractory (R/R) mature T- and NK-cell neoplasms have limited treatment options after standard therapies fail, prompting a study on the effectiveness of the drug tislelizumab.
  • The phase 2 study involved 77 patients grouped into three cohorts based on their specific conditions, observing response rates and treatment outcomes over varying follow-up periods.
  • Results showed promising efficacy in cutaneous T-cell lymphoma (cohort 3) with a 45.5% overall response rate while other cohorts (1 and 2) had more modest success; the treatment was generally well tolerated with mostly mild side effects.
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Background: Whether autologous hematopoietic stem cell transplantation (ASCT) improves the survival of patients with peripheral T-cell lymphoma (PTCL) remains controversial. Some studies have demonstrated that the efficacy of ASCT is superior in patients with complete remission (CR), whereas patients with partial remission (PR) remain vulnerable to relapse after ASCT, resulting in decreased survival rates. Maintenance therapy after chemotherapy may reduce the relapse rate of PTCL and improve survival; however, the role of maintenance therapy after ASCT in PTCL remains unclear.

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