ABSTRACT:Bemiltenase alfa, a factor X (FX) activator derived from Daboia russelii siamensis venom, was developed as a hemostatic agent for hemophilia A and B with inhibitors (HAwI and HBwI). We conducted 2 consecutives multicenter, open-label clinical trials. The phase 1b/2a study assessed the safety, hemostatic efficacy, and pharmacokinetic/pharmacodynamic characteristics of bemiltenase alfa at a dose of 0.1 U/kg. The phase 2b study further evaluated the safety and efficacy at a dose of 0.1 U/kg. Primary efficacy end points encompassed the effective hemostasis rate, safety assessment, and antidrug antibody (ADA) development. There were 6 participants enrolled in the phase 1b study, 20 in phase 2a, and 25 in phase 2b. Patients received bemiltenase alfa for bleeding episodes in the phase 2a and 2b studies. In phase 2a, the effective hemostasis rate was 94.1% (95% confidence interval [CI], 88.7-97.4). Phase 2b showed a rate of 81.9% (95% CI, 71.0-92.9). Most adverse events were mild with grade 1 severity, with no serious events. ADA was detected in 5 patients, but no impact on efficacy and safety was found. Pharmacokinetic findings showed repeated doses of bemiltenase alfa resulted in progressive drug concentration, as indicated by the accumulation ratio index. Pharmacodynamic results indicated a reduction in activated partial thromboplastin time and an increase in thrombin generation peak. Furthermore, a mild decline in FX activity was observed postadministration. The study demonstrates FX activation as a novel hemostatic strategy, with snake venom-derived bemiltenase alfa showing promising safety and efficacy for treating bleeding episodes in patients with HAwI and HBwI. These trials were registered at www.clinicaltrials.gov as #NCT05027230 and #NCT06289166.

Lymphoma is one of the most common hematological malignancies (1). In China,an estimated 5,840 new cases and 2,232 deaths were attributable to Hodgkin lymphoma,whereas 108,327 new cases and 39,905 deaths were attributable to non-Hodgkin lymphoma in 2023 (2,3).

Elderly people are facing an increasing burden of non-Hodgkin lymphoma. However, accurate information on the NHL burden among elderly people remains limited. On the basis of the Global Burden of Diseases 2021, we described the global burden of non-Hodgkin lymphoma in people aged ≥ 65 years and estimated the effects of age, period, and birth cohort on disease burden. The estimated number of prevalent cases among people aged ≥ 65 years was 1,147,321 worldwide in 2021. The age-standardized prevalence rate was 148.21 per 100,000 population. There were 306,296 new cases and 158,813 deaths. The age-standardized rates of incidence and mortality were 59.20 and 21.46 per 100,000 population, respectively. The disease burden was greater in men than in women, and it varied across regions. High-sociodemographic index countries recorded the highest age-standardized incidence and mortality rates, while low-sociodemographic index countries exhibited relatively low incidence rate but high mortality rate. From 1990 to 2021, the incidence and prevalence tended to increase, whereas mortality and disability-adjusted life years tended to decrease. Age effects tended to increase overall mortality risk with increasing age. Period effects showed improvements in mortality after 2004, and cohort effects revealed progressively lower mortality risks in successive birth years after 1922. It is estimated that the age-standardized incidence rate will be relatively stable, whereas the age-standardized mortality rate is expected to decline rapidly by 2035. A focus on elderly men and the implementation of region-specific improvements in clinical diagnosis and treatment are needed.

Breast cancer patients receiving myelosuppressive chemotherapy are at high risk of febrile neutropenia (FN). Long-acting G-CSFs are recommended for FN prevention, but evidence for mecapegfilgrastim in the dose-dense setting remains limited. This multicenter, prospective, observational, real-world study was conducted at 43 centers in China. Patients with breast cancer who received 2-weekly or 3-weekly chemotherapy with mecapegfilgrastim (6 mg) as prophylaxis for chemotherapy-induced neutropenia were enrolled. The primary outcome was the incidence of FN, defined as an oral temperature of > 38.3 °C or two consecutive readings of > 38.0 °C for 2 h and an absolute neutrophil count (ANC) of < 0.5 × 109/l, or expected to fall below 0.5 × 109/L. The secondary outcomes included severe neutropenia and adverse events (AEs). Between June 2019 and March 2022, a total of 757 patients were enrolled. After 1:2 propensity score matching, 36 patients were included in the 2-weekly group and 71 patients were included in the 3-weekly group. In the first cycle, FN, grade 3/4 neutropenia, and grade 4 neutropenia occurred in 0 (0

The advent of novel targeted and immunotherapeutic approaches, particularly Bruton's tyrosine kinase inhibitors (BTKis), have significantly improved survival outcomes in patients with mantle cell lymphoma (MCL), with acceptable safety profiles. However, therapeutic challenges (e.g. acquired resistance, intolerance, etc.) remain. Rocbrutinib is a highly selective, 4th-generation BTKi that integrates the advantages of covalent irreversible inhibition and non-covalent binding, and demonstrates superior pharmacokinetic profiles in humans. Previously, data have demonstrated that rocbrutinib induces high response rate and durable responses in heavily pre-treated patients with R/R MCL, particularly those with prior BTKi exposure (Yuqin Song et al. 2023 ASH). Here, we present updated data from the ongoing phase I trial LP-168-CN101 (NCT04993690) evaluating rocbrutinib in patients with BTKi naïve R/R MCL. Methods Patients aged 18–80 with R/R MCL who had received ≥1 line of therapies (including ≥1 line anti-CD20 antibody-based regimens) were treated with rocbrutinib monotherapy until disease progression. Adverse events (AEs) were graded per CTCAE v5.0, and efficacy was assessed per Lugano 2014 criteria. Results As of June 15, 2025, 28 BTKi-naïve R/R MCL patients were enrolled and received rocbrutinib 100 mg (n=4), 150 mg (n=23), or 200 mg (n=1) once daily (QD) treatment. The median age was 61 years (range: 40–77). Blastoid/pleomorphic variants accounted for 17.9% of cases, and 45.7% of patients were with intermediate- or high-risk per MCL international prognostic index (MIPI). The median number of prior lines of therapies was 1 (range: 1-3), with 14.3% of patients having undergone autologous stem cell transplantation. The most common treatment-related AEs (TRAEs, incidence≥20%) (any grade;≥grade 3) included decreased neutrophil count (46.4%; 7.1%), decreased platelet count (39.3%; 3.1%), increased blood creatinine (35.7%; 0), decreased white blood cell count (32.1%; 0), petechiae (32.1%; 0), anemia (28.6%; 0), and decreased lymphocyte count (21.4%; 0), most of which were grade 1. No atrial fibrillation,≥grade 3 hypertension or hemorrhage occurred. Dose interruption due to TRAEs occurred in 6 (21.4%) patients, but only 1 patient underwent dose reduction. No drug discontinuation or death due to TRAEs has occurred. Of 28 efficacy evaluable patients, the overall response rate (ORR) was 89.3%, with a complete response (CR) rate of 57.1%. After median follow-up of 21.2 (range: 0.9-43.1) months, PFS is not matured yet. The 18-month PFS rate was 74.3%. Conclusion Consistent with previously reported data in patients with post BTKi R/R MCL, rocbrutinib demonstrates a favorable safety profile and robust efficacy in patients with BTKi naïve R/R MCL, with high response rates, deep remissions, and durable responses.

BACKGROUND:Mitoxantrone hydrochloride liposome (Lipo-MIT) exhibits encouraging efficacy in treating multiple hematologic malignancies. This study evaluated the real-world efficacy and safety of Lipo-MIT-containing regimens in the treatment of acute myeloid leukemia (AML). METHODS:This noninterventional, ambispective cohort study was conducted at 42 centers in China. Patients with newly diagnosed or relapsed/refractory AML who received Lipo-MIT-containing regimens were included. The primary endpoint was the composite complete remission (CRc) rate. RESULTS:Between January 2022 and December 2023, 117 patients with newly diagnosed AML and 122 patients with relapsed/refractory AML were included. The CRc and objective response rates were 84.6% (95% confidence interval [CI], 76.8-90.6) and 91.5% (95% CI, 84.8-95.8), respectively, in the newly diagnosed AML, and 45.1% (95% CI, 36.1-54.3) and 55.7% (95% CI, 46.5-64.7), respectively, in relapsed/refractory AML. The 2-year-event-free survival and overall survival rates for newly diagnosed AML were 67.0% (95% CI, 54.4-76.8) and 77.8% (95% CI, 63.8-86.9), respectively, while the rates for relapsed/refractory AML were 23.9% (95% CI, 12.5-37.3) and 56.9% (95% CI, 39.6-70.9), respectively. Univariate and multivariate analyses suggested age and the number of prior failed induction therapy cycles as independent prognostic factors for CRc in relapsed/refractory AML (all P < .05). Treatment-related adverse events (AEs) were reported in 216 patients (90.4%). Thrombocytopenia (64.4%), leukopenia (63.6%), and neutropenia (60.7%) were the most common AEs of grade 3-4. No treatment-related deaths occurred. CONCLUSIONS:Lipo-MIT-containing regimens were effective and well-tolerated in AML under real-world circumstances. TRIAL REGISTRATION ID:ChiCTR2200067172.

Preclinical studies of tifcemalimab (anti-BTLA antibody) in combination with toripalimab (anti-PD-1 antibody) demonstrated synergistic anti-tumor effects. We present the outcomes of tifcemalimab with or without toripalimab in lymphoma patients. This is a 2-part, phase I study (NCT04477772). In Part A (dose escalation based on 3 + 3 design), patients with relapsed or refractory lymphoma received tifcemalimab monotherapy 1, 3 or 10 mg/kg for dose escalation and 3 mg/kg or 200 mg for dose expansion. For Part B (indication expansion), only classical Hodgkin's lymphoma (cHL) patients were included to receive tifcemalimab 100 or 200 mg plus toripalimab 240 mg due to poor tumor response in other subtypes. The primary endpoints were safety, maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D). 25 patients in Part A and 46 in Part B were enrolled. No dose-limiting toxicities were observed, and MTD was not reached. The RP2D for tifcemalimab was 200 mg. Adverse events were predominantly Grade 1/2. Grade 3/4 treatment-related adverse events occurred in 3 patients (12·0%) in Part A and 15 patients (32·6%) in Part B. No fatal adverse events were observed. Tifcemalimab with or without toripalimab demonstrated a favorable safety profile in lymphoma patients.

Introduction: Chemotherapy-induced thrombocytopenia (CIT) is a common complication resulting from the myelosuppressive effects of cytotoxic regimens. It frequently necessitates dose reductions, treatment delays, or platelet transfusions, which could compromise the efficacy of anticancer therapy. However, no widely approved therapies are currently available to address this clinical gap. This phase III trial was designed to evaluate the efficacy and safety of hetrombopag, a potent oral thrombopoietin receptor agonist, in patients with CIT. Methods: This randomized, double-blind, placebo-controlled phase III study (ClinicalTrials.gov: NCT05864014) enrolled patients with malignancies experiencing ≥7-day chemotherapy delay due to thrombocytopenia (platelet count <75×10⁹/L) following platinum-based combination regimens. Eligible patients were randomly assigned 1:1:1 to Arm I (hetrombopag), Arm II (hetrombopag administered only prior to the initiation of the first chemotherapy cycle [C1], with subsequent switch to placebo) or the Control Arm (placebo). Stratification factors included baseline platelet count (≥50 vs <50×10⁹/L) and immune checkpoint inhibitor use. The starting dose of investigational medicinal product was 7.5 mg/day which could be titrated to a maximum of 15 mg/day. The primary endpoint was the proportion of treatment responders, defined as patients who: (1) achieved platelet recovery (≥100×10⁹/L) within 14 days; (2) completed C1 and maintained a platelet count ≥75×10⁹/L at C1 Day 21 (+4 days) without the use of platelet rescue therapy. Results: Between April 27, 2023, and March 3, 2025, a total of 337 patients underwent screening, of whom 213 were randomized to Arm I (n = 70), Arm II (n = 72), or the Control Arm (n = 71). The median age of enrolled patients was 61.0 years, and 79.3% of patients had a baseline platelet count of ≥50×10⁹/L. The most common tumor types were gastric cancer (36.2%) and colorectal cancer (46.9%). Most patients (88.1%) were undergoing front-line or adjuvant therapy at enrollment. The third-generation platinum-based regimen was administered to 88.3% of patients, while 20.9% received chemo-immunotherapy and 18.5% chemo-targeted regimens. For the primary endpoint, treatment response rates were 75.7% (53/70) in the Arm I, 48.6% (35/72) in the Arm II, and 39.4% (28/71) in the Control Arm, respectively. A statistically significant improvement in response rate was observed in Arm I compared with the Control Arm (+36.2 percentage points; 95% CI: 21.0 to 51.3; p<0.0001), whereas no clinically meaningful difference was observed between Arm II and the Control Arm (difference +9.0 percentage points; 95% CI -7.2 to 25.1; p=0.2757). Patients in Arm I sustained median platelet counts >100×10⁹/L at all post-chemotherapy visits; and the median platelet counts were 104.0×10⁹/L (Arms I), 67.5×10⁹/L (Arms II), and 66.0×10⁹/L (Control Arm), respectively at Cycle 2 Day 21 (C2D21). The median delay in initiating C2 was 1.5 days in Arm I, compared with 13.0 days in Arm II and 12.0 days in the Control Arm. Notably, increased patients in Arm I could complete two cycles (C1 and C2) without platelet-related treatment modifications or rescue therapy while maintaining a platelet count ≥75×10⁹/L at C2D21 (Arm I 62.9% [44/70] vs. Arm II 9.7% [7/72] vs. Control Arm: 5.6% [4/71]). Treatment-emergent adverse events occurred in 90.0% (Arm I), 91.5% (Arm II), and 92.9% (Control Arm) of patients, predominantly grade 1-2. Critically, no treatment-related adverse events of special interest including prespecified liver function abnormalities, thrombotic events, or World Health Organization (WHO) grade ≥2 bleeding were observed in hetrombopag-treated arms (Arms I and II). Conclusions: In patients with CIT from solid tumors, continuous hetrombopag administration throughout chemotherapy cycles maintained stable platelet counts and thereby facilitated on-schedule full-dose chemotherapy with a favorable safety profile, addressing an unmet clinical need and offering a viable oral strategy for CIT management.

Infections are frequent complications in patients with hematological disorders, and pathogen diagnosis remains challenging. Metagenomic next-generation sequencing (mNGS) is an unbiased high-throughput technology that has been widely applied in the diagnosis of infectious diseases. However, to date, there are no established international guidelines or expert consensuses regarding the use of mNGS to diagnose infections in patients with hematologic disorders. The Anti-Infection Study Group of the Chinese Society of Hematology invited experts in the fields of hematology, microbiology, and mNGS technology to draft an expert consensus focused on clinical indications, sample collection, quality control, and interpretation of results. This consensus will likely contribute to clarifying the medical indications for mNGS testing, optimizing the interpretation of reports, and becoming an inspiration for global practice.

BackgroundHodgkin Lymphoma is a rare lymphatic system malignancy which has a negative impact on the health of children and adolescents. While high-income regions have seen a decline in mortality rates due to early diagnosis and advances in treatment strategies (e.g., chemotherapy, radiotherapy, and targeted therapy), low- and middle-income countries continue to face high mortality rates due to limited medical resources and delayed treatment.MethodsEmploying data from the Global Burden of Disease (GBD) 2021 study, this analysis assessed the burden of Hodgkin lymphoma among children and adolescents from 1990 to 2021. Metrics including incidence, mortality, and disability-adjusted life years (DALYs) were evaluated across Socio-demographic Index (SDI) quintiles. Age-Period-Cohort (APC) and Nordpred models were used to analyze long-term trends and project future disease burden. Additionally, joinpoint regression analysis identified significant temporal shifts in trends throughout the study period.ResultsThe estimated DALY number was 265,016, and the ASDR among children and adolescents was 9.816 per 100,000 person in 2021. There were 8,700 new HL cases and 3,385 deaths, and the ASIR and ASMR were 0.320 and 0.125 per 100,000 population, respectively. The estimated number of prevalent HL cases was 50,128 worldwide with the ASPR of 2.001 per 100,000 population. Globally, the Hodgkin lymphoma burden was consistently higher in male children and adolescents than in females across all metrics. Results reveal a global decline in age-standardized incidence rates of HL among children and adolescents, with significant regional variations. Low- and middle-income regions experienced an increase in HL burden, while high-income regions showed a decline trend. The case number of HL in the children and adolescents increased from 8,283 in 1990 to 8,700 in 2021, while ASIR declined by 9.52%. The APC model projected a continued decline in HL incidence and mortality globally by 2040. However, health inequalities persist, with low-income countries bearing a disproportionately high burden of HL.ConclusionsThe burden of HL among children and adolescents is increasing, with a significant difference by sex, age and regions, which highlight the urgent need for equitable diagnostic and therapeutic access in low-resource settings to meet the 2030 SDG targets on child health.

Background:Next-generation sequencing (NGS) offers a method for measurable residual disease (MRD) assessment by detecting leukemia-associated genetic mutations. Objective:This study aimed to evaluate the clinical implications and prognostic value of NGS-based MRD assessment in acute myeloid leukemia (AML). Design:Sixty-nine adult AML patients were included for NGS (targeted sequencing of AML-related 47 genes), of which 56 patients at initial diagnosis, 69 patients in the first day of consolidation therapy (C1D1), and 51 patients during 2-year MRD monitoring (detection following the C1D1) were enrolled. Methods:Mutation data were categorized into gene mutations, somatic mutations and somatic mutations excluding clonal hematopoiesis of indeterminate potential (CHIP) for analysis. The study also integrated multiparameter flow cytometry (MFC) and NGS data at C1D1 to evaluate the prognostic significance of combining the two MRD techniques. Results:Mutation detection rates were 98.21%, 69.57%, and 84.31% for AML patients at initial diagnosis, C1D1 stage, and MRD monitoring, respectively, identified by targeted sequencing. During MRD monitoring, the ETV6 mutation frequency was significantly higher in relapsed patients than in non-relapsed patients (p < 0.05). The mean variant allele frequency (VAF) was significantly higher in the 2-year MRD monitoring period (0.160 ± 0.155) compared to the C1D1 period (0.058 ± 0.087; p < 0.05) in relapsed patients. Survival analysis revealed that patients with a mean VAF (somatic mutations excluding CHIP) ⩽0.004 in the C1D1 stage and ⩽0.020 during MRD monitoring had a better prognosis. Furthermore, the combination of MFC and NGS-based MRD (somatic mutations excluding CHIP) at C1D1 stage showed that patients who were negative for two tests had longer survival than those who were negative for only one. Conclusion:The combined assessment of MFC-MRD and NGS-MRD status provides a refined prognostic stratification, with the absence of somatic mutations and MFC-MRD negativity correlating with improved progression-free survival, which is expected to improve clinical prognostic assessment of AML patients.

Rocbrutinib, a highly selective, 4th-generation Bruton's tyrosine kinase (BTK) inhibitor, uniquely takes advantages of both covalent irreversible inhibition for wide-type BTK and non-covalent binding for C481-mutant variants. Here, we present the safety and efficacy results from the ongoing phase I trial (LP-168-CN101; NCT04993690) of rocbrutinib in Chinese patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). Eligible patients aged 18–80 with a confirmed diagnosis of CLL/SLL were treated with rocbrutinib monotherapy until disease progression or intolerable toxicity. Adverse events (AEs) were graded per CTCAE v5.0, and response was evaluated per 2018 iwCLL criteria. As of April 15, 2025, 41 (untreated (1L), n=12; relapsed/refractory (R/R) BTKi-naïve, n=17; R/R post-BTKi, n=12) CLL/SLL patients were enrolled and treated with rocbrutinib (100 mg ,n=1; 150 mg, n=28; 200 mg, n=10; 300mg, n=2) once daily. The median age was 60 (range, 35-79) years. Of the patients with evaluable samples, 26.9% (7/26) with del(17p), 42.9% (12/28) with TP53 mutation, 63.0% (17/27) with unmutated IGHV and 44.0% (11/25) with complex karyotype. Of the 29 R/R CLL/SLL patients, the median number of prior therapies was 2 (range, 1-5), including prior covalent BTKis (34.5%), BCL2 inhibitors (BCL-2i, 24.1%), and noncovalent BTKis (6.9%). In R/R post-BTKi CLL/SLL patients, most (91.7%) discontinued prior BTKi due to disease progression; 41.6% had prior BCL-2i ; 6/9 (66.7%) carried BTK mutations, including BTKC481S, BTKC481Y/R and BTKL528W. The most common treatment-related AEs (TRAEs, incidence≥20%)(any grade;≥grade 3) included decreased neutrophil count (41.5%; 19.5%), anemia (36.6%; 2.4%), decreased platelet count (29.3%; 2.4%), hyperuricemia (26.8%; 0) and rash (22.0%; 0), most of which were grade 1. No ≥grade 3 atrial fibrillation, hypertension or hemorrhage occurred. Dose interruption due to TRAEs occurred in 8 (19.5%) patients, however, only 1 (2.4%) patient underwent dose reduction. No drug discontinuation or death due to TRAEs has occurred. In 1L patients (n=12), the overall response rate (ORR, partial response with lymphocytosis or better) was 91.7%. The ORR and complete remission (CR)/CR with incomplete marrow recovery (CRi) rates in R/R BTKi-naïve patients (n=17) were 100% and 17.6%, respectively. In R/R post-BTKi patients, rocbrutinib monotherapy achieved 75% ORR including16.7% CR/CRi. In BTKi and BCL-2i double refractory population (n=5), ORR and CR/CRi rates were 80.0% and 40.0%, respectively; 3 patients are still in remission while the other 2 patients both had durable response of more than 17 months. 2 patients with BTKL528W mutation achieved PR and are still on treatment (DOR: 8.1 and 14.0 months). After median follow-up of 7.4 months, all 12 1L patients remained on treatment. In the R/R BTKi naive population (median follow-up 15.8 months), the estimated 12-month PFS rate as 94.1% (95% CI: 65.0-99.1); In the R/R post-BTKi population (median follow-up 15.5 months), the estimated 12-month PFS rate as 83.3% (95% CI: 48.2-95.6). Rocbrutinib has a favorable safety profile and shows durable responses in patients with CLL/SLL, including those with prior BTK inhibitor exposure and/or with covalent and noncovalent BTKi-resistant mutations.

Mecapegfilgrastim has been previously validated for efficacy and safety in neutropenia prevention during clinical trials. This nationwide, real-world study (RWS) evaluates its role in protecting against moderate to severe chemotherapy-induced neutropenia (CIN) in Chinese patients with non-myeloid malignancies. In this prospective study conducted in the 46 centers across China, the patients with non-myeloid malignancies were enrolled, and received subcutaneous injections of mecapegfilgrastim 24 h after each chemotherapy cycle. Outcomes were monitored over four subsequent chemotherapy cycles. The primary outcome was safety, while secondary outcomes included the incidence of grade 3 or higher neutropenia, grade 4 neutropenia, and febrile neutropenia (FN), etc. From June 2019 to March 2022, 2,859 patients were enrolled, contributing to 7,763 observed chemotherapy cycles. Treatment-related adverse events (TRAEs) were noted in 329 patients (11.5

Background: Peripheral T-cell lymphoma (PTCL) represents a heterogeneous group of aggressive lymphomas, accounting for 25%–30% of non-Hodgkin lymphomas (NHL) in China. The CHOP regimen remains the standard first-line treatment for PTCL, yet its long-term efficacy requires improvement. Relapsed or refractory (R/R) PTCL is highly aggressive with extremely poor survival outcomes, exhibiting a 3-year overall survival (OS) rate of less than 30%. This MOMENT study demonstrated promising efficacy and safety of the mitoxantrone hydrochloride liposome (Lipo-MIT)-based regimen in PTCL (J Leuk Lymphoma, 2023, 32(8): 457-464). Nevertheless, additional data are warranted to establish further validation. We previously reported updated real-world evidence for Lipo-MIT in treatment-naïve (TN) PTCL (2025 EHA, #PF949), showing a complete response (CR) rate of 48.2% and objective response rate (ORR) of 83.6%. Herein, we present updated survival outcomes for Lipo-MIT in TN-PTCL and provide the most recent real-world evidence regarding Lipo-MIT in R/R PTCL. Methods: This multicenter, non-interventional, ambispective cohort real-world study was registered at www.chictr.org.cn (ChiCTR2200062067). It enrolled adult patients diagnosed with TN or R/R PTCL. The primary endpoint was ORR. Secondary endpoints included CR rate, progression-free survival (PFS), OS, and safety. Results: As of February 8, 2025, 609 patients were enrolled, comprising 494 with relapsed/refractory PTCL (R/R PTCL) and 115 with treatment-naïve PTCL (TN-PTCL). The R/R cohort had a median age of 56 years (range: 19–86) with 62.1% males; subtypes included angioimmunoblastic T-cell lymphoma (AITL, 30.0%), extranodal NK/T-cell lymphoma (NKTCL, 25.9%), PTCL not otherwise specified (PTCL-NOS, 24.9%), ALK-negative anaplastic large cell lymphoma (ALCL, ALK-, 5.9%), ALK-positive ALCL (ALCL, ALK+, 2.8%), and other subtypes (10.5%). Advanced-stage (III–IV) disease was present in 67.0% pts, 27.9% had International prognostic index (IPI) scores 3–5, and 21.1% exhibited B symptoms. Prior therapy exposure included: ≥1 lines in all patients (50.4% first-line, 21.3% second-line, 28.3% ≥third-line), with 74.9% previously receiving anthracyclines. Patients received Lipo-MIT-containing regimens for a median of 3 cycles (range: 1–11), with median Lipo-MIT doses of 17.7 mg/m² (monotherapy: range 11.2–20.3 mg/m²; combination: range 5.4–23.3 mg/m²). Among 456 efficacy-evaluable R/R patients, the overall response rate (ORR) was 62.1% (283/456) and complete response (CR) rate was 29.2% (133/456), with ORR varying by subtype: AITL 68.6% (96/140), NKTCL 60.8% (73/120), PTCL-NOS 57.5% (65/113), ALCL ALK- 51.9% (14/27), and ALCL ALK+ 61.5% (8/13). Response rates decreased with prior lines: 68.1% (160/235) after first-line, 61.6% (61/99) after second-line, and 50.8% (62/122) after ≥third-line therapy. With a median follow-up of 6.5 months, median progression-free survival (PFS) was 9.9 months (95% CI: 7.1–12.7) and median overall survival (OS) was not reached. In the TN cohort (n=115), median follow-up was 11.6 months with median PFS of 14.6 months (95% CI: 10.8–18.3); 1-year PFS rates was 58.6%. Median OS was not reached, with 1-year OS rates of 88.0%. Safety analysis of the full cohort (n=609) revealed treatment-related adverse events (TRAEs) in 89.0% (542/609), with grade ≥3 TRAEs in 66.0%. Predominant hematologic toxicities included neutropenia (46.6%), leukopenia (42.2%), lymphopenia (34.5%), anemia (22.5%), and thrombocytopenia (23.0%). Non-hematologic TRAEs were primarily grade 1–2; no unexpected or serious adverse events were observed. Conclusion: Lipo-MIT-based regimens demonstrated favorable clinical efficacy and tolerability in both TN-PTCL and R/R PTCL, representing a promising therapeutic option. Continued follow-up for survival outcomes is ongoing, with additional results forthcoming.

Background: Chemotherapy-induced thrombocytopenia (CIT) increases the risk of bleeding, necessitates chemotherapy dose reductions and delays, and negatively impacts prognosis. Objectives: This study aimed to evaluate the efficacy and safety of hetrombopag for the management of CIT in patients with advanced solid tumors. Design: A multicenter, randomized, double-blind, placebo-controlled, phase II study. Methods: Patients with advanced solid tumors who experienced a chemotherapy delay of >= 7 days due to thrombocytopenia (platelet count <75 x 10(9)/L) were randomly assigned (1:1) to receive oral hetrombopag at an initial dose of 7.5 mg once daily or a matching placebo. The primary endpoint was the proportion of treatment responders, defined as patients resuming chemotherapy within 14 days (platelet count >= 100 x 10(9)/L) and not requiring a chemotherapy dose reduction of >= 15% or a delay of >= 4 days or rescue therapy for two consecutive cycles. Results: Between 9 October 2021 and 5 May 2022, 60 patients were randomized, with 59 receiving >= 1 dose of assigned treatment (hetrombopag/placebo arm, n = 28/31). The proportion of treatment responders was significantly higher in the hetrombopag arm than in the placebo arm [60.7% (17/28) versus 12.9% (4/31); difference of proportion: 47.6% (95% confidence interval (CI): 26.0-69.3); odds ratio = 10.44 (95% CI: 2.82-38.65); p value (nominal) based on the Cochran-Mantel-Haenszel: <0.001)]. During the double-blind treatment period, grade 3 or higher adverse events (AEs) occurred in 35.7% (10/28) of patients with hetrombopag and 38.7% (12/31) of patients on placebo. The most common grade 3 or higher AEs were decreased neutrophil count [35.7% (10/28) versus 35.5% (11/31)] and decreased white blood cell count [17.9% (5/28) versus 19.4% (6/31)]. Serious AEs were reported in 3.6% (1/28) of patients with hetrombopag and 9.7% (3/31) of patients with placebo. Conclusion: Hetrombopag is an effective and well-tolerated alternative for managing CIT in patients with solid tumors.

Bruton's tyrosine kinase inhibitors (BTKis) have revolutionized the treatment of B-cell lymphomas. However, safety issues related to the use of BTKis may hinder treatment continuity and further affect clinical efficacy. A comprehensive and systematic expert consensus from a pharmacological perspective is lacking for safety issues associated with BTKi treatment. A multidisciplinary consensus working group was established, comprising 35 members from the fields of hematology, cardiovascular disease, cardio-oncology, clinical pharmacy, and evidence-based medicine. This evidence-based expert consensus was formulated using an evidence-based approach and the Delphi method. The Joanna Briggs Institute Critical Appraisal (JBI) tool and Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach were used to rate the quality of evidence and grade the strength of recommendations, respectively. This consensus provides practical recommendations for BTKis medication based on nine aspects within three domains, including the management of common adverse drug events such as bleeding, cardiovascular events, and hematological toxicity, as well as the management of drug-drug interactions and guidance for special populations. This multidisciplinary expert consensus could contribute to promoting a multi-dimensional, comprehensive and standardized management of BTKis.

Background: Secondary acute myeloid leukemia (sAML) is an aggressive subset of acute myeloid leukemia (AML). sAML is more prevalent in older patients (pts) and is associated with adverse biological features, as well as a multi-drug resistance phenotype that contributes to the limited efficacy of conventional induction therapies. Although newly approved drugs and regimens, such as CPX-351 and venetoclax combined with hypomethylating agents (HMAs), have shown promising efficacy in sAML-with composite complete remission (CRc) rates ranging from 48% to 60%. However, the outcomes for pts with adverse-risk cytomolecular features are still suboptimal. Mitoxantrone has been shown to exhibit partial non-cross-resistance with anthracyclines. Mitoxantrone hydrochloride liposome (Lipo-MIT) is a pegylated liposomal formulation of mitoxantrone that offers enhanced efficacy and lower toxicity. We hypothesize that Lipo-MIT combined with cytarabine (MA) based regimens could demonstrate improved outcomes in newly diagnosed sAML pts. Methods: Data of adult pts with newly diagnosed sAML from an ongoing prospective study and a real-world study were collected. The definition of sAML was that AML pts with a history of myelodysplastic syndromes (MDS) or CMML, MDS-related cytogenetics, and/or exposure to prior chemotherapy or radiotherapy for another malignancy. Enrolled patients were required to have an Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less. Patients received MA-based regimens consisted of Lipo-MIT and cytarabine with/without other drugs up to 2 cycles. Rate of CRc (complete remission (CR)+CR with incomplete neutrophil or platelet recovery (CRi)), CR/CRi with negative minimal residual disease (MRD), overall response rate (ORR), event-free survival (EFS), overall survival (OS) and safety were analyzed. Results: A total of 14 pts were enrolled, including 10 with therapy-related AML and 4 with AML arising from antecedent MDS. The median age was 56.5 years (range, 22.0-65.0). The French-American-British (FAB) subtypes were as follows: M1 in 2 pts (14.3%), M2 in 6 pts (42.9%), M5 in 5 pts (35.7%), and 1 patient (7.1%) without a specific subtype. According to the 2022 edition of the European Leukemia Network recommendations, 3 (21.4%) were classified as having a favorable prognosis, 3 (21.4%) as intermediate, 7 (50.0%) as adverse, and 1 (7.1%) as unknown. TP53 was the most commonly mutated gene identified in 25.0% of 12 pts who underwent molecular examination. Karyotype analysis was conducted in 12 pts, revealing abnormalities in 8 pts (66.7%), with the most frequent abnormality being del(7q) observed in 25.0%. Of 14 pts, 12 (85.7%) received MA regimen, 1 (7.1%) received MA+venetoclax (MAV) regimen and 1 (7.1%) received MA+granulocyte colony stimulating factor (G-CSF) regimen. Median dose of Lipo-MIT was 23.6 mg/m2 (range 12.0-26.0). As of the data cut-off on July 30, 2024, the CRc rate was 64.3% (9/14) and the ORR was 71.4% (10/14). Among 4 pts who did not achieve ORR, 2 pts had a reduction in bone marrow blasts of more than 50%. Patients classified as favorable/intermediate risk had a higher CRc of 83.3% (5/6) while adverse group was 42.9% (3/7). Additionally, among 9 pts achieving CR/CRi, flow cytometry were available for 7 pts, revealing a rate of negative MRD of 85.7% (6/7). At a median follow-up time of 4.68 months (range, 1.1-28.7), 4 pts occurred treatment failure, 1 patient died and 2 pts loss of follow-up. The median EFS and OS were not reached. Among pts achieving remission in cycle 1, the median duration of absolute neutrophil count <1000 cells/μL was 21.0 days (range, 12.0-31.0) and platelet count <25000 platelets/μL was 12.0 days (range, 6.0-41.0). The most common non-hematological treatment-emergent adverse events graded at 3 were fever (21.4%), sepsis (14.3%), pulmonary infection (7.1%), anaphylaxis (7.1%) and pruritus (7.1%). No adverse events of grade 4 or worse were observed and the mortality rate of 60-day was 0%. Conclusions: Lipo-MIT combined with cytarabine-based regimens achieved encouraging rates of CRc and MRD negativity in newly diagnosed sAML with a well tolerated safety profile. Larger sample size and prolonged follow-up time are needed.