This Phase I/II clinical trial (NCT04471064) evaluated the preliminary efficacy, safety, and pharmacokinetics of XY0206, a novel oral FMS-like tyrosine kinase 3 (FLT3) inhibitor, in patients with relapsed or refractory acute myeloid leukemia (R/R AML). From September 2020 to December 2022, this open-label, multicenter study enrolled patients aged ≥ 18 years with R/R AML. The trial included dose-escalation and dose-expansion phases, with six cohorts receiving XY0206 at doses ranging from 12.5 to 62.5 mg once daily or 25 mg twice daily. Of the 61 enrolled participants, 37 had FLT3 mutation-positive (FLT3mut+) AML. The overall response rate (ORR) was 34.4% in the entire cohort and 48.6% in FLT3mut+ patients. Among FLT3mut+ patients, the composite complete remission rate (CRc) was 45.9%, including a complete remission (CR) rate of 5.4% and a CR with partial hematologic recovery (CRh) rate of 13.5% and a CR with incomplete hematologic recovery (CRi) rate of 27.0%. In patients with FLT3 internal tandem duplication (FLT3-ITD) mutations, the ORR was 56.7%, with a CRc of 53.3% (CR: 6.7%; CRh: 16.7% ; CRi: 30.0%). The 37.5 mg dose cohort, identified as the target dose, was expanded exclusively for FLT3mut+ patients. XY0206 exhibited a favorable safety profile and demonstrated potent antileukemic activity, particularly in FLT3mut+ R/R AML patients, supporting its further clinical development. Trial Registration: CTR20201214 (CDE); ClinicalTrials.gov ID: NCT04471064.

BackgroundBlinatumomab, a bispecific T-cell engager (BiTE), has significantly improved the efficacy of B-ALL treatment. However, its association with immune effector cell-associated neurotoxicity syndrome (ICANS) has garnered increasing attention. This study analyzes two cases of ICANS to explore the challenges in recognizing clinical symptoms and standardizing management.Case presentationCase 1 involved a 69-year-old male with B-ALL, harboring TP53 and DNMT3A mutations, who developed grade 2 ICANS following blinatumomab treatment. Therapy was continued without interruption, and symptoms resolved with levetiracetam intervention. Case 2 was a 29-year-old male with B-ALL and ETV6::RUNX1 fusion gene, who developed grade 4 ICANS (seizures, impaired consciousness, epileptic episodes) on day 4 of blinatumomab therapy. The patient required intensive care and comprehensive intervention, leading to symptom resolution but discontinuation of treatment. Neither case exhibited central nervous system infiltration, and cranial CT scans showed no abnormalities.Discussion and conclusionICANS may be associated with cytokine release, blood-brain barrier disruption, and genetic background, presenting with heterogeneous symptoms. Elderly patients or those with specific genetic mutations may face increased risks, necessitating individualized dose adjustments (e.g., stepwise dosing) and close monitoring of neurological functions and cytokines (e.g., IL-6). Early recognition of subtle symptoms (e.g., tremors) combined with corticosteroids and antiepileptic drugs can improve outcomes. The use of blinatumomab requires careful balancing of efficacy and neurotoxicity, particularly in high-risk patients. This case report provides valuable insights for the clinical recognition and management of ICANS.

6506 Background: Venetoclax has been approved for the treatment of newly diagnosed acute myeloid leukemia (AML) in elderly or unfit pts but failed in the high-risk myelodysplastic syndromes (MDS). Mesutoclax is a novel, potent, highly selective BCL-2 inhibitor. It exhibits favorable pharmacokinetic profile without any major metabolites. Methods: ICP-CL-01205 (NCT06656494) is an ongoing, global, phase I study evaluating mesutoclax in combination with azacitidine (AZA) in pts with AML or MDS. In the dose escalation part, mesutoclax at100 mg, 125 mg, and 150 mg in combination with AZA were evaluated for safety and tolerability. 100 mg and 125 mg were selected as Recommended dose for expansion (RDE) for further evaluation. Antitumor activity in AML and MDS is assessed based on ELN 2017 and IWG 2006/2023 criteria, respectively. Herein, we report safety, tolerability and efficacy for mesutoclax with AZA in pts with AML and MDS in this phase 1 study. Results: As of January 12, 2026, a total of 59 pts were enrolled including 8 R/R AML, 39 TN AML and 12 TN MDS. The median age of AML and MDS pts was 65 (range: 23, 81) and 67 years (range: 54, 75), respectively. Adverse risk per 2017 ELN was identified in 51.1% AML pts. Azole prophylaxis and G-CSF treatment were used in 5% and 22% pts. Among the 35 evaluable TN AML pts, 30 (85.7%) achieved composite CR (cCR, CR+CRi) with central assessment of CR rate of 65.7% (23/35). Among those who achieved cCR, 86.7% (26/30) were MRD negative per flow cytometry. MRD negative in CR (CR MRD- ) was 60% (21/35). cCR was 75% in adverse risk per 2017 ELN classification. The DOR rate at 3-months was 91.7%. The 6-month OS rate was 94.1%. Among 10 response evaluable TN MDS pts, the overall response rate (ORR) per IWG 2006 criteria was 100%, including CR in 20%, marrow CR in 80%. The composite CR rate was 70% per IWG 2023 criteria including 30% CR even when most pts only received 1 cycle treatment. There were no DLT or TLS events. The most common (≥10%) grade ≥ 3 TEAEs in pooled analysis of 59 AML and MDS were neutrophil count decreased (62.7%), platelet count decreased (50.8%), anemia (33.9%), infection (16.9%), and lymphocyte count decreased (11.9%). There were 5.1% grade ≥ 3 febrile neutropenia and no TEAEs lead to dose discontinuation. SAEs were reported in 25.4% pts. For pts with TN AML, the median intervals between cycle 1 and cycle 2 initiation (requiring neutrophil ≥1*10 9 /l and platelet ≥ 100*10 9 /l) was 39 days and the median duration of grade 4 neutropenia and thrombocytopenia were 17 and 9 days, respectively. Conclusions: The combination of mesutoclax and azacitidine demonstrated a favorable safety profile and encouraging anti-tumor activity not only in AML but also in MDS pts, supporting its continued development for the treatment of myeloid malignancies. These preliminary results warrant further investigation in larger, randomized trials. Clinical trial information: NCT06656494 .

Background Homoharringtonine (HHT) suppresses the expression of the CCAAT/enhancer-binding protein alpha (CEBPA). Our previous retrospective analysis indicated that favorable outcomes were observed in acute myeloid leukemia (AML) with double-mutated CEBPA (CEBPAdm) when patients received an HHT-based induction regimen. To confirm these observations, we performed a prospective multicenter, single-arm trial to assess the efficacy of homoharringtonine, daunorubicin, and cytarabine (HAD) induction regimen in patients with CEBPAdm AML. Methods This prospective multicenter single-arm trial enrolled patients with newly diagnosed CEBPAdm AML who received the HAD induction regimen between June 1, 2020, and October 1, 2023. Consolidation therapy comprised three cycles of high-dose cytarabine (HDAC). The trial was registered at ClinicalTrials.gov (NCT04415008). The primary outcomes were event-free survival (EFS) and relapse-free survival (RFS). Secondary endpoints included complete remission (CR) rate, 30-day mortality, and overall survival (OS). Survival outcomes were estimated using the Kaplan-Meier method and compared with the log-rank test. Results A total of 61 patients with newly diagnosed CEBPAdm AML (median age 40 years, interquartile range [IQR] 30–47 years) were enrolled. After one course of HAD induction, 57 patients (93.44%) achieved complete remission (CR), and the overall CR rate after one or two courses reached 95.08% (58/61). Among the 58 responders, 46 patients (79.31% [46/58]) achieved measurable residual disease (MRD) negativity after the first induction. The 30-day mortality rate was 3.28% (2/61). At a median follow-up of 31.97 months (IQR 21.27–37.77), the estimated 3-year EFS, RFS, and OS rates were 77.86%, 82.16%, and 87.27%, respectively. Exploratory subgroup analyses showed a numerical trend toward inferior RFS in patients with the co-occurring colony stimulating factor 3 receptor (CSF3R)T618I mutation (P = 0.064); however, given the small subgroup size, these findings are hypothesis-generating only and require validation in larger cohorts. Conclusions The HAD regimen demonstrated promising clinical activity and an acceptable safety profile in young adult patients with CEBPAdm AML, with 3-year EFS and RFS rates that met the predetermined objectives of 72% and 75%, respectively. Trial registration No. NCT04415008; https://classic.clinicaltrials.gov.

e23343 Background: Adult patients with relapsed/refractory (R/R) extramedullary B-ALL have a dismal prognosis with conventional therapies. Despite the success of CD19 CAR-T in hematologic relapse, its efficacy in extramedullary disease remains underexplored, as pivotal trials often excluded these high-risk pts. This large, multicenter, real-world study aims to define the outcomes of Inaticabtagene autoleucel (Inati-cel) in this challenging population. Methods: Eligible patients had R/R extramedullary B-ALL, underwent apheresis for Inati-cel following its approval (November 7, 2023), and completed at least 30 days of follow-up. The primary endpoints were overall survival (OS) and relapse-free survival (RFS). Secondary outcomes included the complete remission (CR) rate, minimal residual disease (MRD) negativity rate, and toxicity profiles. CR was defined as ≤5% bone marrow blasts morphologically, no circulating lymphoblasts, and resolution of extramedullary disease. MRD was evaluated via flow cytometry, RQ-PCR, and/or NGS. CRS and ICANS were graded according to ASTCT criteria. Results: As of the data cutoff (December 31, 2025), a total of 50 patients with R/R extramedullary B-ALL from over 20 centers across China received Inati-cel therapy. The median age was 39.5 years (range, 14–79), and 60% were male. Extramedullary disease involved the central nervous system (CNS) in 64%(32/50) of pts, non-CNS disease in 28%(14/50), and both in 8%(4/50). Following infusion, 41 of 48 evaluable pts (85.4%) achieved CR in both bone marrow and EM disease, with 100% of responders achieving bone marrow MRD negativity. Among pts with CNS involvement, the CR rate was 93.3% (28/30), compared with 78.6% (11/14) in those with non-CNS EM disease and 50% (2/4) in pts with both CNS and non-CNS EM disease. After a median follow-up of 7.2 months, the median OS and RFS had not been reached; Notably, the 1-year OS and RFS rates were 86.8% and 61.9%, respectively. Compared to their Ph-positive counterparts, patients with Ph-negative disease had significantly worse OS (100% vs 76.4%; P = 0.026) and RFS (81.2% vs 45.6%; P = 0.039). Similarly, IKZF1 deletion was associated with significantly poorer OS (89.4% vs 66.7%; P = 0.044) and RFS (67.1% vs 33.3%; P = 0.004). Regarding safety, any-grade CRS occurred in 66% of pts (4% Grade 3–4), and ICANS occurred in 14% (4% Grade 3). All toxicities were manageable and reversible, with no treatment-related deaths. Conclusions: This largest real-world study demonstrates that commercial CD19 CAR-T therapy with Inati-cel induces high response rates and durable survival in adult patients with high-risk R/R extramedullary B-ALL, exhibiting a manageable safety profile. These findings establish Inati-cel as an effective standard-of-care option for this population and support its use even in settings typically excluded from clinical trials.

Abstract Background Treatment outcomes for high-risk B-ALL remain suboptimal. Blinatumomab, a CD19/CD3 bispecific T-cell engager, has shown efficacy in trials, but real-world data in Chinese high-risk patients are limited. Methods This single-center retrospective study analyzed 29 high-risk B-ALL patients treated with blinatumomab (7–28 days/cycle). We assessed short-term efficacy (MRD negativity rate), safety, and the impact of genetic factors and treatment duration. Results The overall MRD negativity rate after one cycle of blinatumomab was 82.8% (24/29). All patients with the Ph-like subtype (3/3, 100%) and 71.4% (10/14) of Ph+ patients achieved MRD negativity. However, clinical outcomes were inferior in patients harboring specific genetic alterations: 50% (2/4) of patients with the BCR::ABL1 T315I mutation experienced early relapse, and only one of two patients with E2A::PBX1 rearrangement achieved transient MRD negativity. The median event-free survival (EFS) was 9.6 months (95% CI: 6–16.75). Grade ≥ 3 hematologic toxicity occurred in 48.3% (14/29) of the patient cohort. Conclusion Blinatumomab achieved high short-term MRD response rates in high-risk B-ALL. Inferior outcomes appeared to be associated with the presence of BCR::ABL1 T315I mutations and E2A::PBX1 rearrangements.

Abstract Before November 2023, CD19 chimeric antigen receptor (CAR) T-cell therapies had not been approved in China for patients with relapsed or refractory B-cell acute lymphoblastic leukemia (R/R B-ALL), leaving a significant unmet need. In response, inaticabtagene autoleucel (Inati-cel), a novel CD19 CAR T-cell therapy with a distinct single-chain variable fragment (HI19α), was developed and showed promising efficacy in preliminary clinical research. We conducted a phase 2, single-arm, multicenter study of Inati-cel in adult CD19+ R/R B-ALL in China. The primary end point was the overall remission rate (ORR) at the end of month 3. Forty-eight patients who underwent Inati-cel infusion were evaluated for both efficacy and safety. Among them, 34 patients achieved and maintained remission beyond 3 months, with a 3-month ORR of 70.8% (95% confidence interval [CI], 55.9-83.1). The best ORR was 85.4%, with all responders reaching minimal residual disease negativity. With a median follow-up of 23.7 months, the median duration of remission was 20.7 months (95% CI, 6.4 to not reached), and the median overall survival was not reached (95% CI, 13.0 months to not reached). Additionally, grade ≥3 cytokine release syndrome and neurologic events occurred in 12.5% and 6.2% of patients, respectively. The 2-year follow-up data suggest that Inati-cel demonstrates encouraging and durable responses with manageable safety profiles in R/R B-ALL. Based on the data from this pivotal trial, Inati-cel was approved as the first CAR T-cell therapy for adult R/R B-ALL in China and underscores its potential therapeutic benefits for this patient population. This trial was registered at www.ClinicalTrials.gov as #NCT04684147.

BACKGROUND:The death rate of hematological malignancies is high, and the death rate of patients with COVID-19 infection is further increased. Although there have been expert consensus and relevant guidelines to introduce the recommendations of the guidelines for patients with hematological malignancies complicated with COVID-19 infection, there is limited understanding of the clinical characteristics of Chinese patients with acute leukemia complicated with COVID-19 infection. AIMS:This study aimed to analyze the clinical manifestations, mortality, and determinants of viral shedding duration in Chinese AL patients infected with COVID-19. METHODS:We conducted a retrospective study of 100 AL patients with COVID-19 infection in Henan Province, China, from December 1, 2022, to January 31, 2023. Data on demographics, leukemia subtype, symptoms, treatments (antibiotics/antivirals), and viral shedding duration were collected. Follow-up was conducted over three months to assess mortality. Univariate and multivariate analyses were performed to identify risk factors. RESULTS:The median age was 49.5 years (58% male, 42% female), with 76% having acute myeloid leukemia (AML) and 24% acute lymphoblastic leukemia (ALL). Most patients (86%) were asymptomatic. Antibiotics and antivirals were administered to 35% and 25% of patients, respectively. Severe cases and fatalities exhibited prolonged viral shedding. Neutropenic patients on antibiotics had significantly extended shedding duration, whereas antiviral therapy or delayed primary disease management shortened it. The overall mortality rate was 6%. Univariate analysis identified neutropenia as a key mortality risk factor, though multivariate analysis showed no significant associations. CONCLUSION:Early antiviral treatment may reduce viral shedding duration and potentially mitigate symptom severity and mortality in AL patients with COVID-19. Neutropenia emerged as a critical factor influencing outcomes. These findings underscore the importance of tailored therapeutic strategies for this high-risk population.

Background and aimMucormycosis is a life-threatening invasive fungal infection. This study aimed to analyze the clinical characteristics of patients with hematologic malignancies complicated with mucormycosis.MethodsThis retrospective study investigated the clinical characteristics, epidemiological features, treatment, and prognosis of 46 patients with hematological diseases and Mucor infection as indicated by mNGS from August 28, 2020 to September 11, 2023. Metagenomic next-generation sequencing (mNGS) refers to the application of high-throughput sequencing technology for the comprehensive analysis of nucleic acid content in patient samples, facilitating the detection and characterization of microbial DNA and/or RNA, and then comparing and analyzing the results with an information database to determine the types of pathogenic microorganisms present in the sample.ResultsThe median age of admission for the included patients was 49 years (9-78). Multivariate analysis identified age over 60 years (p = 0.006 < 0.05), high-dose corticosteroids (p = 0.001 < 0.05), neutropenia lasting more than 10 days (p = 0.041 < 0.05), and two or more Mucor infections (p = 0.004 < 0.05) were independent risk factors for OS in patients with hematological diseases. Moreover, differences between groups were analyzed using the Fisher exact probability method, and no significant difference was observed in the efficacy of various types of antifungal therapies.ConclusionPatients with hematologic malignancies benefit greatly from early diagnosis and treatment when suspected of Mucor infection. mNGS is an important supplementary method for early diagnosis of Mucor infection. Moderated use of corticosteroids, reducing the duration of neutropenia, and enhancing autologous immune function are important measures to reduce patient mortality rate.

Abstract Background: Acute leukemia is the most common hematological malignancy, mainly including acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). Nucleophosmin 1 mutations (mNPM1) occur in 20%-30% of AML patients. Patients with mNPM1 have a 5-year survival rate of ~50%, with a median overall survival (OS) of 6.1-7.3 months in relapsed/refractory (R/R) patients. The gene rearrangement of the lysine methyltransferase 2A (KMT2Ar) occurs in ~10% of acute leukemia patients. Patients with a KMT2A rearrangement have a 5-year survival rate of ~20%-25%, with a median OS 2.4-6 months in R/R patients. Menin is a scaffolding protein that interacts with aberrant NPM1 or KMT2A to upregulate the HOXA/MEIS1 pathway, resulting in leukemogenesis. Menin inhibitors are a new class of targeted therapy that inhibit the interaction of menin and KMT2A, thus allowing differentiation of blasts. Zefamenib is a potent small molecule inhibitor targeting menin. In mouse studies, zefamenib has been shown to significantly reduce the tumor burden and reduce the proliferation of leukemia cell in peripheral blood, bone marrow, and spleen. Zefamenib has also demonstrated anti-leukemia efficacy and safety in relapsed/refractory acute leukemia patients in a phase 1 dose escalation/dose optimization study; results were presented at ASH in 2024. Of the 28 patients with mNMP1 or KMT2Ar treated with the RP2D of 600 mg BID, the overall response rate and CR/CRh rate was 89.3% and 57.1%, respectively. No patient had a dose-limiting toxicity, and the toxicity profile was acceptable with 2 pts with grade 1 QT prolongation and 2 pts with grade 2 differentiation syndrome. This study is currently enrolling in the phase 2 portion and is designed to evaluate the efficacy, safety, pharmacokinetics (PK), and efficacy of zefamenib in Chinese patients with relapsed/refractory acute leukemia. Study Design and Methods: This study (NCT06052813) is a phase 2, multicenter, open-label study of zefamenib monotherapy in Chinese patients with relapsed/refractory acute leukemias who have either a KMT2A or or an NPM1 gene mutation. Key eligibility criteria include patients diagnosed with relapsed/refractory acute leukemia (including AML, ALL, and mixed lineage leukemia, excluding acute promyelocytic leukemia) according to the World Health Organization 2022 criteria, bone marrow morphological changes (blasts/immature cells ≥5%), confirmed NPM1 gene mutation or KMT2A or NUP98 rearrangement, and meet one of the following four conditions: (i) primary refractory disease; (ii) first relapse and duration of first response ≤12 months; (iii) relapsed/refractory disease after 2 or more lines of therapy; (iv) relapse after allogeneic hematopoietic stem cell transplantation. Zefamenib will be administered twice daily for 28-day treatment cycles until disease progression/recurrence, intolerable toxicity, loss to follow-up, withdrawal of informed consent, death, or the investigator's judgment to terminate the study drug, whichever occurs first. The primary objective of the phase 2 dose expansion phase is to evaluate the efficacy of zefamenib in 30-48 patients using the RP2D dose obtained in phase 1. The patients will be divided into 3 cohorts (10-16 patients per cohort): (A) patients with AML with NPM1 mutations; (B) patients with AML with KMT2A rearrangements; and (C) other patients, including patients with relapsed/refractory ALL or mixed lineage leukemia with KMT2A rearrangement; patients with AML with NUP98 rearrangement; patients with AML or ALL with other types of gene alterations that meet protocol requirements. The primary endpoint for the phase 2 dose expansion phase CRc (CR+CRh+CRi). Key secondary endpoints include CR, CR+CRh, objective response rate, MRD negative remission rate, duration of response, duration of CR+CRh, duration of CRc, EFS, OS, cumulative relapse rate, cumulative mortality, safety, and pharmacokinetics. Based on the phase 1 results of this study, a global phase 2 study assessing the efficacy and safety of zefamenib monotherapy in acute leukemias with NUP98r, HOXA9r, or mNPM1 will be started in Q2 2026.

ObjectiveTo evaluate the clinical efficacy of maintenance therapy with sorafenib combined with interferon α-1b, interleukin-2, and thalidomide (the ITI regimen) in patients with FLT3-ITD-positive acute myeloid leukemia (AML).Methods19 FLT3-ITD(+) AML patients were retrospectively analyzed, who received the sorafenib combined with ITI regimen as maintenance therapy after achieving remission at Affiliated Cancer Hospital of Zhengzhou University (January 2014–December 2024). Minimal residual disease (MRD) levels were monitored, and clinical outcomes, including survival duration, were assessed.ResultsThis study included 19 patients (9 males, 10 females) with a median age at diagnosis of 59 years (range: 21–76). The median white blood cell count was 32.25×109/L (range: 0.7–254×109/L). Among them, 13 patients (68.4%) maintained sustained MRD negativity during sorafenib combined with TI regimen therapy, while 3 patients experienced morphological relapse and 3 had molecular relapse. Median overall survival (mOS) was not reached, with 12- and 24-month OS rates of 100% (19/19) and 94.7% (18/19), respectively. During maintenance therapy with sorafenib combined with ITI, median relapse-free survival (mRFS) was also not reached, with 12- and 24-month RFS rates of 73.7% (14/19) and 57.9% (11/19), respectively.ConclusionThe sorafenib combined with ITI regimen is an effective maintenance therapy for FLT3-ITD (+) AML, significantly reducing relapse risk and prolonging survival.

Abstract Introduction: Inaticabtagene autoleucel (Inati-cel), featuring a CD19 scFv derived from the HI19a clone and a 4-1BB/CD3-ζ costimulatory domain, was approved in China for adult patients with r/r B-ALL and demonstrated high MRD-negative CR/CRi rate (85.4%) and an estimated 2-year OS rate of 55.2% (Wang Y et al. Blood Adv. 2025). Here, we report the real-world outcomes with more patients and key subgroups described. Methods: The multi-center real-world study (NCT06450067) was conducted from 2023. The endpoints included overall remission rate (ORR), minimal residual disease (MRD) negativity rate, overall survival (OS), relapse-free survival (RFS) and other relevant measures. Both OS and RFS were calculated from the day of Inati-cel infusion. Results: From November 20, 2023, to July 22, 2025, 210 patients underwent leukapheresis, with 156 receiving Inati-cel and 145 included in efficacy and safety analyses. Fifty-four patients underwent apheresis but did not receive the infusion due to manufacture failure (4 pts: 1 for insufficient lymphocytes in the apheresis product, 1 for low CD4/CD8 ratio, and 2 for unknown reasons) or infection (2 pts), or still waiting for infusion. The median age was 39 years (range, 13-76), with 28 patients aged≥60 years. Patients were pretreated with a median of 1 prior lines of therapy (range 1-5). Prior immunotherapies included: HSCT (21.4%), inotuzumab ozogamicin (18.6%), and blinatumomab (28.3%). There were 81 (55.9%) R/R ALL patients:15 (10.3%) primary refractory and 26 (17.9%) with extramedullary lesions, and 64 (44.1%) in CR1 (12 MRD-positive and 52 MRD-negative). About 50% carried high-risk genetic abnormity such as TP53 deletion or mutation (7.6%), MLL rearrangement (9.7%), alterations of IKZF1 (16.6%), Ph-like (4.8%), alterations of PAX5 (5.5%). The median infusion dose was 0.60 (range: 0.42-1.14) ×108CAR-T live cells, with 88% of patients receiving bridge therapy. With a median follow-up of 6.18 months (range: 0.85–19.13months), the BOR in all patients was 92.4% (134/145), and among the cases with remission, the MRD negativity rate was 97.8%. In R/R ALL caess, the BOR and MRD negativity rate were 86.4% (70/81) and 97.1%, respectively. Among the 12 patients with MRD-positive, the MRD-negativity rate reached 100%. Of the 26 patients with extramedullary disease, the ORR was 80%; notably of the 16 patients with CNSL, 15 attained CR. Of the 71 patients with available MRD results assessed by q-PCR or NGS for IG rearrangement after Inati-cel, 87.3% achieved MRD negative. Following infusion, expansion of Inati-cel was observed, even in patients with MRD-negative CR prior to infusion, with peaking around day 14. The longest detectability lasted up to 15 months post-infusion in a patient maintaining CR. The median OS, RFS and DOR have not been reached. The estimated 1-year OS, RFS and DOR rates were 89.3%, 78.1% and 84.7%, respectively. Seven proceeded to allo-HSCT following Inati-cel. Among all responsed patients no significant differences were observed in OS and RFS (P = 0.59 and 0.60, respectively) regardless of the subsequent transplant status, however, significant difference in RFS was observed between patients with subsequent anti-tumor treatment and those without (P = 0.003). Thirteen relapses were observed, with 6 CD19-positive, 6 CD19-negative, and 1 with unknown CD19 status. In the univariate analysis, the number of prior treatment lines, age, previous exposure to blinatumomab, or inotuzumab ozogamicin, and prior history of HSCT were not identified as significant prognostic factors for RFS and OS. A total of 9 patients died: 5 died from disease progression, 2 from transplant-related complications, 1 from infection, and 1 from unknown causes. The most common adverse events (AEs) of special interest were cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). The incidence rates of CRS and ICAN were 53.8% and 4.9%, respectively, while grade ≥3 CRS and ICANS occurring in 2.8% and 2.8%, respectively. All patients recovered without sequelae, with 38 treated with corticosteroids, and 33 with tocilizumab or siltuximab. Conclusion: Real-world data on Inati-cel corroborates its robust response rate, favorable toxicity profile, and survival benefits. Inati-cel demonstrates efficacy in patients with active extramedullary diseases, particularly those with CNSL. In vivo expansion was observed across different disease states.

Introduction Inaticabtagene autoleucel (Inati-cel) featuring a CD19 single-chain variable fragment derived from an HI19a clone and a 4-1BB/CD3-ζ costimulatory domain has been approved in China for adult patients with relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). Inati-cel yielded a high minimal residual disease (MRD)-negative complete remission (CR)/CR with incomplete count recovery (CRi) rate (85.4%) and an estimated 2-year overall survival (OS) rate of 55.2% (Wang Y. et al., Blood Adv, 2025). Adding tyrosine kinase inhibitors (TKIs) significantly improves the prognosis of Ph-positive (Ph+) B-ALL. However, some patients remain resistant to conventional therapies or relapse post-treatment. Emerging evidence indicates that chemotherapy-free treatments for Ph+ B-ALL are associated with high rates of molecular response and favorable survival outcomes. Herein, we evaluate the efficacy and safety of Inati-cel in Ph+ B-ALL patients. Methods We conducted a multi-institutional real-world study of Inati-cel (NCT06450067), enrolling patients treated since 2024. Endpoints included OS, complete hematologic response, complete molecular response, relapse-free survival (RFS), and other relevant measures. OS and RFS were calculated from the day of Inati-cel infusion. Results From January 8, 2024, to July 20, 2025, 156 patients received Inati-cel, among whom 54 cases with Ph+ B-ALL underwent efficacy and safety evaluations. Their median age was 45 years (range: 15–76 years), with 13 patients (24.1%) aged ≥ 60 years. The patients had received a median of 1 prior line of therapy (range: 1–5). Prior therapies included hematopoietic stem cell transplantation (HSCT) (24.1%), inotuzumab ozogamicin (14.8%), and blinatumomab (24.1%). Patients with R/R disease and those in first complete remission (CR1) each accounted for 50%. Fourteen patients had extramedullary relapses, including 13 with central nervous system leukemia (CNSL). The median infusion dose was 0.60 (range: 0.44–1.00) × 108viable CAR-T cells, with 88.9% of patients receiving bridge therapy. The median interval from apheresis to infusion was 38 days (range: 23–181). With a median follow-up of 6.25 months (range: 0.95–16.93), the best overall response rate (ORR) in the R/R patients was 96.7%; among responders, the MRD negativity rate (assessed using flow cytometry) was 100.0%. All 5 patients with baseline MRD positivity achieved MRD negativity after Inati-cel administration. Of the 48 patients with available BCR/ABL1 fusion genes assessed using q-PCR post-infusion, 87.5% achieved negativity. Notably, of the 13 patients with CNSL, the ORR was 92.3%. Post-infusion, Inati-cel expanded even in patients with MRD-negative CR pre-infusion, with peak levels observed around day 14. The longest duration of detectability was 15 months post-infusion in a patient in sustained CR. Detectable CAR-T cells were observed in the cerebrospinal fluid of some patients. No patients underwent subsequent allo-HSCT while in remission; most received maintenance therapy with TKIs, with the longest RFS exceeding 16 months. The median OS and RFS were not reached in the overall population. In the R/R and CR1 patients, the estimated 1-year OS and RFS rates were 93.3% and 84.7%, respectively, and 100% and 95.2%, respectively. In a univariate analysis, IKZF1 abnormalities, prior exposure to inotuzumab ozogamicin, and the fusion gene turning negative after Inati-cel use were not significant prognostic factors for RFS or OS. Three relapses were documented: 1 with CD19 positivity, and 2 with CD19 negativity. Five patients exhibited persistent BCR/ABL1 fusion gene positivity, and 3 experienced fusion gene relapses. One patient died from unknown causes (more than 3 months after Inati-cel infusion). The most common adverse events of interest were cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). CRS occurred in 50.0% of patients, with only 1 case of grade 3; ICANS developed in 2 patients-both grade 1. All patients recovered without sequelae: 9 received corticosteroids, and 11 received tocilizumab. Conclusion Real-world data demonstrate that Inati-cel exhibits excellent efficacy in patients with Ph+ B-ALL, yielding low toxicity, short treatment cycles, high complete molecular response rates, and favorable long-term survival. Extended follow-up could illuminate the long-term outcomes of Inati-cel use.

OBJECTIVE:To retrospectively investigate the short-term efficacy and safety of the triple-drug combination regimen of venetoclax + azacitidine + homoharringtonine (VAH regimen) in patients with acute myeloid leukemia (AML). METHODS:Retrospective analysis was conducted on a total of 45 patients with newly diagnosed or refractory/relapsed AML, who were admitted to the Affiliated Cancer Hospital of Zhengzhou University, the First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, the Huaihe Hospital of Henan University, and The First Affiliated Hospital of Xinxiang Medical University from July 2022 to October 2024 and treated with the VAH regimen. The overall response rate and safety of this regimen were analyzed, and the relevant literature was reviewed. RESULTS:In the 23 newly treated patients, the overall response rate (ORR) (CR+CRi) was 65.2 % on day 15 of the VAH regimen and 82.6 % on day 29 after the end of cycle 1. The median duration of grade 3-4 neutropenia was 12.6 days. In the 22 refractory/relapsed patients, the ORR (CR+CRi) was 68.2 % on day 15 of the VAH regimen and 86.4 % on day 29 after the end of cycle 1, and the median duration of neutropenia was 14.4 days. The most common adverse reactions were myelosuppression and infection, both of which were within controllable limits. There was no death due to adverse reactions during treatment. CONCLUSION:The VAH regimen yields a high remission rate in newly diagnosed and refractory/relapsed AML patients. This retrospective study provides a novel treatment strategy for AML patients.

Abstract Introduction Treating acute myeloid leukemia (AML), a diverse group of hematological cancers affecting bone marrow and blood, remains difficult, with a five-year survival rate of about 30%. Although screening for genetic mutations and fusion genes has become essential in AML diagnosis and risk stratification, the clinical significance of copy number aberrations (CNAs) remains poorly understood. To this end, we conducted a multicenter prospective clinical trial (ChiCTR2300077695) to characterize the genomic landscape of CNAs using shallow whole-genome sequencing (sWGS), termed LeukoPrint, in AML. Interim results from the first 205 patients (pts) are reported here. Methods In this prospective multicenter clinical trial, we aim to enroll 600 newly diagnosed AML pts (excluding APL) across 13 participating hospitals in China. Bone marrow samples were collected and underwent CNA profiling via LeukoPrint (1× sWGS) at three stages: pretreatment, post-induction, and relapse. CNAs only those greater than 5 Mbp were analyzed. Conventional karyotyping analysis was performed in parallel for this cohort, and its diagnostic performance was compared with LeukoPrint. European Leukemia Net (ELN)-defined CNAs were used for risk stratification, consistent with standard cytogenetic analysis protocols. The trial received approval from the Ethics Committees of all participating hospitals, and all pts provided informed consent. By April 9, 2025, 205 pts were enrolled in this study, with 136 in the younger group (aged 18–59) and 69 in the older group (aged ≥60). All pts underwent CNA profiling using LeukoPrint at least twice, at pretreatment and post-induction phases. Results Using LeukoPrint, we detected 193 CNAs in 87 pts (42.4% of the cohort). No notable difference in detection rates was observed between younger and older groups (41.9% vs. 43.5%). CNAs were frequently identified in chromosomes 7, 8, 11, and Y (each with >5% prevalence), with the most common recurrent CNAs occurring at 8q24.21 (13% prevalence), the locus containing the MYC oncogene. Recurrent deletions were predominantly observed in 5q31.3 and 7q36.1, the genomic regions harboring the oncogenes ACSL6, CD74, and EZH2. LeukoPrint outperformed karyotyping in CNA detection (42.4% vs. 27.3%), enhancing results for 51 pts (24.9% of the cohort). Notably, 38 pts, initially classified with normal karyotypes or failed karyotyping, were reclassified as carrying CNAs. Applying the 2022 ELN criteria, three pts initially classified as low- or intermediate-risk based on genetic mutations, fusions, and karyotypes were reclassified as high-risk following LeukoPrint analysis in place of karyotyping. Clinical follow-up in two cases confirmed poor outcomes in one, supporting LeukoPrint’s prognostic value. LeukoPrint demonstrates strong potential for prognostic prediction by monitoring dynamic change of molecular response in 115 pts. A significantly higher proportion of pts with post-induction CNAs were identified as non-responders than those without CNAs (6 vs. 3). Similarly, the proportion of pts without detectable post-induction CNAs was 95.5% in complete remission (CR, n=22), 83.3% in CR with partial hematologic recovery (CRh, n=6), 71.4% in CR with incomplete hematologic recovery (CRi, n=7), 0% in partial remission (PR, n=3), and 0% in non-responders (NR, n=3). Copy-neutral loss of heterozygosity (CN-LOH) occurs when one allele is lost and the remaining allele is duplicated, resulting in no net change in copy number. This genomic alteration, such as TP53 CN-LOH, can have significant clinical impact but is undetectable by traditional karyotyping or fluorescence in situ hybridization (FISH). LeukoPrint identified CN-LOH in 43 (20.9%) of 205 pts in this cohort. Notably, CN-LOH was detected in 25 out of 114 pts without detectable CNAs, revealing that LeukoPrint provides additional insights into chromosomal aberrations in 12% (25/205) of pts. Combined with 24.9% from standard LeukoPrint analysis, LeukoPrint enhanced CNA detection in at least 36.9% of pts. Conclusions LeukoPrint outperforms traditional karyotyping in detecting CNAs, improving data accuracy in over one-third of pts in this cohort. It enables dynamic monitoring of treatment response and disease progression, demonstrating strong correlation with clinical outcomes. These findings suggest that LeukoPrint holds significant promise as a complementary or alternative tool for conventional cytogenetic methods in AML.

Objective:To investigate the efficacy and safety of venetoclax (Ven) in combination with hypomethylating agents (HMAs) for the treatment of mixed-phenotype acute leukemia (MPAL). Methods:From July 2023 to April 2025, 4 newly diagnosed MPAL patients treated with Ven combined with HMAs at the Affiliated Cancer Hospital of Zhengzhou University, Luoyang Central Hospital and Anyang Regional Hospital were retrospectively analyzed to determine the efficacy and safety of this treatment. The relevant published studies were reviewed. Results:This study included four patients (2 males, 2 females) with a median age of 47 years (range: 40-80 years). Three patients were classified as having B/myeloid MPAL, and one was classified as having T/myeloid MPAL. All patients achieved complete remission (CR) after one cycle of venetoclax combined with HMAs. Notably, Patient 3, who tested positive for the BCR::ABL1 fusion gene, received additional tyrosine kinase inhibitor (TKI) therapy. The median duration of myelosuppression during induction therapy was 26 days (range: 7-36). Patients 1 and 4 developed infections during induction, which were controlled with aggressive antimicrobial treatment and supportive care. In contrast, Patients 2 and 3 tolerated the regimen well without significant adverse events. Conclusion:The treatment of MPAL with Ven combined with HMAs achieved a high remission rate and can be used as an alternative treatment for MPAL.

Introduction Blinatumomab, a bispecific antibody targeting CD3/CD19, can significantly improve the complete remission (CR) rate, measurable residual disease (MRD) clearance, and survival in patients with relapsed and refractory (R/R) or newly diagnosed B-ALL, especially those with MRD-positive (MRD+) disease. Although clinical studies and guidelines recommend administering blinatumomab in a 28-day cycle, prospective studies have shown that a 14-day short course of blinatumomab combined with low-dose chemotherapy for first-line treatment is not significantly different from the standard cycle in terms of early efficacy. However, the clinical efficacy of short-course blinatumomab remains not fully understood. AIMS To compare the differences in CR rate, MRD negative rate, and survival outcomes between the 14-day and >14-day courses of blinatumomab in B-ALL patients. To assess the clinical benefit for patients receiving a shortened 14-day course of blinatumomab. METHODS: This multicenter retrospective study was conducted from March 2022 to July 2025 on patients with B-ALL who had detectable leukemia burden, defined as being at least MRD-positive, after one cycle of standard chemotherapy or those who were relapsed or refractory. These patients were treated with blinatumomab as reinduction therapy and were divided into two cohorts: those with a treatment duration of ≤14 days (12-14 days) and those with a treatment duration of >14 days. The outcomes assessed included CR rate, MRD-negative rate, overall survival (OS), and progression-free survival (PFS), with comparisons made between the two cohorts. Hematopoietic toxicity, cytokine response syndrome (CRS), and infections were also evaluated. RESULTS: A total of 119 B-ALL patients with detectable leukemia burden were analyzed, including those with high leukemia burden (>50% blast cells) (n = 36), intermediate burden (5-50%) (n = 35), and low burden (≤5% and MRD+) (n = 48). These patients received either ≤14 days (12-14) (n = 50) or >14 days of blinatumomab (n = 61), including 21 days (15-21 days) (n = 30) and 28 days (22-28 days) (n=31). Cohort analysis revealed no significant differences in CR/CRi rates (76.67% vs. 76.19%, P = 0.99) and MRD-negative rates (66.67% vs. 73.81%, P = 0.602) between the two cohorts of ≤14 days and >14 days of blinatumomab for reinduction therapy in patients with medium-to-high leukemia burden. Similarly, there was no significant difference in the MRD-negative rate (89.47% vs. 90%) between the two cohorts in patients with MRD-positive status prior to blinatumomab. The MRD-negative rate in patients with medium-to-high leukemia burden was significantly lower than in those with a low burden (70.83% vs. 89.74%, P = 0.03). For patients who had not achieved CR/CRi or MRD negativity after 14 days of blinatumomab (n = 37), extending treatment to 21 or 28 days did not significantly increase the CR/CRi rate or MRD negativity rate. Notably, in high-load patients (n = 17) who received >14 days of blinatumomab treatment, the CR/CRi rate and MRD-negative rate were 70.59% (12/17) and 88.24% (15/17), respectively, which were slightly higher than those at 14 days (both CR rate and MRD-negative rates were 64.71% (11/17)). However, the differences were not statistically significant (both P values were > 0.05). For MRD+ patients (n = 9), the MRD-negative rate at 14 days was 77.78% (7/9), which remained unchanged at 21 days. With a median follow-up of 21.47 months, the median progression-free survival (PFS) in the 14-day cohort was 9.90 months, compared to 9.33 months in the >14-day cohort. The 1-year PFS rates were 46.6% (95% CI 36.2-60.1) and 46.4% (95% CI 34.7-62.2), respectively, with no significant differences observed between the two cohorts. Regarding toxicity, there were no significant differences in the incidence and severity of CRS between the two cohorts. Lymphocyte depletion was more pronounced in the >14-day cohort, with an infection rate of 49.27% (34/69), which was significantly higher than the 28% (14/50) in the ≤14-day cohort (P = 0.0036). However, there was no significant difference in infections of grade ≥ 3. CONCLUSIONS: Recognizing the limits of a retrospective comparison, a 14-day course of blinatumomab yields response rates and survival outcomes similar to the standard course, particularly in patients with a low leukemia burden. Patients with high tumor burden may benefit from more than 14 days of treatment.