Venclexta (venetoclax) / Roche, AbbVie - LARVOL DELTA

Real-world efficacy of inaticabtagene autoleucel in adult B-cell acute lymphoblastic leukemia patients with high-risk molecular alterations (ASH 2025) - P | "The CR1-MRD⁻ group exhibited a trend toward superior median RFS compared to the combined CR1-MRD⁺ and R/R group (not reached vs. 404 days [95% CI: 30-777 days], P=0.073).In terms of post-CAR-T management, 20 patients received combination therapy (including three patients received tyrosine kinase inhibitors, one patients received zanubrutinib, two patients received pomalidomide, three patients received venetoclax, one patients received blinatumomab, one patients received inotuzumab ozogamicin, and four patients received allo-HSCT), while 21 patients underwent observation only. Front-line consolidation with CAR-T during CR1-MRD⁻ in patients with high-risk molecular alterations may yield better RFS outcomes compared to treatment administered in R/R or MRD⁺ settings. No RFS benefit from post-CAR-T combination therapy was observed in this cohort, highlighting the need for validation with longer follow-up durations and larger patient cohorts."

Clinical • IO biomarker • Real-world • Real-world effectiveness • Real-world evidence • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • IKZF1 • KMT2A • TP53

Venetoclax and Obinutuzumab Followed by Epcoritamab for the Treatment of Untreated Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma, LonGEVity Trial (clinicaltrials.gov) - P2 | N=33 | Recruiting | Sponsor: City of Hope Medical Center | Not yet recruiting ➔ Recruiting | Trial completion date: Aug 2028 ➔ Jun 2029 | Trial primary completion date: Aug 2028 ➔ Jun 2029

Enrollment open • Trial completion date • Trial primary completion date • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma

Phase 1/2, multi-center, open-label clinical study to evaluate the safety, pharmacokinetics, and efficacy of Zefamenib combined with chemotherapy or targeted Agents in patients with Acute Myeloid Leukemia (ASH 2025) - P1/2 | "Menin inhibitor revumenib combined with venetoclax and azacitidine have shown complete remission (CR) rate of 88.4% in newly diagnosed AML patients harboring these aberrations...Cohort A and D will enroll untreated AML patients, who will receive zefamenib combined with standard 7+3 chemotherapy for induction and zefamenib combined with high dose cytarabine for consolidation...This study will be the first to clarify the feasibility of zefamenib with intensive chemotherapy or targeted agents in the frontline treatment of AML patients or the efficacy and safety of zefamenib with targeted agents in R/R AML patients harboring NPM1 mutation or KMT2A/NUP98 rearrangements. Results of this study will provide ideas and evidence to improve the prognosis of Chinese AML patients with these genetic aberrations."

Clinical • P1/2 data • PK/PD data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • KMT2A • MEIS1 • NPM1 • NUP98

Tagraxofusp and low-intensity chemotherapy for the treatment of CD123-positive relapsed or refractory Acute Myeloid Leukemia (ASH 2025) - P1/2 | "Background and Significance: The combination of venetoclax and a hypomethylating agent (Ven/HMA) is the standard frontline (1L) therapy for patients with acute myeloid leukemia (AML) who are ineligible for intensive chemotherapy (IC)...Cladribine (CLAD) with low-dose cytaratbine (LDAC) has previously been shown to be well-tolerated and effective in IC-ineligible patients with newly diagnosed AML...The study began enrolling patients in January 2025 and is actively recruiting. Clinical Trial Registration NCT06561152"

IO biomarker • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • BCL2 • CD123 • IL3RA

Trials in progress: Phase IB/II of CPX-351 as maintenance therapy in AML patients ineligible for bone marrow transplantation (ASH 2025) - "In patients ineligible for allogenic hematopoietic stem cell transplant (HSCT), oral azacitidine is the only FDA approved treatment option...Eligible patients are newly diagnosed with AML in CR that have received any induction regimen with standard consolidation or a hypomethylating agent (HMA) and venetoclax, for at least 6 cycles and no more than 12 cycles...Prior HSCT patients are excluded, as well as cumulative lifetime anthracycline (doxorubicin equivalent) dose equal to or greater than 345 mg/m2, and for patients with prior mediastinal radiation therapy, anthracycline dose equal to or greater than 295 mg/m2...This investigator-sponsored study was supported by a research grant and provision of study drug from Jazz Pharmaceuticals. The study was independently designed and conducted by the investigators."

Clinical • P1/2 data • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Transplantation

Trial in progress: Phase II Study of (early) combination salvage therapy with venetoclax and intensified decitabine in relapsed/refractory AML (VenSwitch) (ASH 2025) - P2 | "A scientific companion program includes spatial assessment of the bone marrow microenvironment under therapy and sequential transcriptomic analyses by single-cell RNA-sequencing of bone marrow samples. The trial started enrollment in November 2023 an has enrolled 18 patients to date."

IO biomarker • P2 data • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Lymphoma • Myelodysplastic Syndrome • FLT3 • TP53

Comparing the efficacy and safety of the ABC-14 regimen (Azacitidine, Venetoclax, and Chidamide) with traditional "3+7" intensive induction regimen or AB-14 regimen (Venetoclax Combined with Azacitidine) in newly diagnosed AML: Study protocol for a prospective, multicenter, randomized, open-label clinical trial (ASH 2025) - P2 | "To provide a alternative treatment for induction therapy of newly diagnosed AML indiscriminately. Trial registration ClinicalTrials.gov NCT06451861, Registered on 2024.06.11, https://clinicaltrials.gov/study/NCT06451861 Keywords Acute myeloid leukemia, unfit-AML, fit-AML, induction therapy, Protocol"

Clinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • FLT3 • MCL1 • RUNX1 • TP53

Trial in progress: Phase I trial to evaluate safety of oral azacytidine in combination with pomalidomide as maintenance therapy in AML (ASH 2025) - "Oral azacitidine has demonstrated improved relapse-free and overall survival in older, transplant-ineligible patients, establishing a role in AML maintenance (Hunault-Berger M Blood Cancer J. 2017). In resource-limited settings, delivery of high-dose cytarabine or allogeneic transplant is frequently compromised due to multidrug-resistant infections, poor performance status (PS), and lack of donors...Participants must have adequate hematologic recovery, ECOG PS 0–2, with no prior exposure to azacytidine or venetoclax...Participants are enrolled sequentially into each cohort to ensure safety. Dose escalation is ongoing as per protocol."

Clinical • Combination therapy • P1 data • Acute Myelogenous Leukemia • Acute Promyelocytic Leukemia • Heart Failure • Hematological Malignancies • Immunology • Infectious Disease • Leukemia • Liver Failure • Nephrology • Renal Disease • CRBN • IKZF1 • IKZF3

Ivosidenib combined with venetoclax and azacitidine for the treatment of newly diagnosed IDH1-mutant Acute Myeloid Leukemia: A prospective, two cohorts, multicenter study (ASH 2025) - "Previous data showed that the multi-drug combination regimen of IVO demonstrates good tolerability and efficacy. This study will be the first to clarify the feasibility of multi-drug regimens in the treatment of IDH1m AML patients in China, providing ideas and evidence to improve the prognosis of Chinese IDH1m AML patients."

Clinical • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • IDH1

Update AML: Updated disease monitoring and treatment to enhance outcomes for pediatric AML (NCT07059975) (ASH 2025) - P1 | "These patients will receive the common salvage regimen Idarubicin-fludarabine-cytarabine (IdaFLA) as the second cycle (Induction 2) in lieu of standard DA8 (Daunorubicin-Cytarabine) chemotherapy...In UPDATE AML, IR patients will receive VIA in place of MA (mitoxantrone-cytarabine) to eliminate exposure to the cardiotoxic agent mitoxantrone. HR patients will receive VIA as Intensification 1 prior to SCT, in place of the genotoxic agent etoposide and to provide venetoclax exposure prior to SCT...All newly diagnosed patients at TXCH >1 month to <30 years old with non-FLT3-ITD+ AML will be eligible for enrollment after completing standard Induction 1 chemotherapy consisting of combination of daunorubicin and cytarabine +/- gemtuzumab...Over 3 years, the study is anticipated to accrue 36-40 patients and generate important feasibility data for our treatment and molecular MRD innovations. Our results will inform future cooperative group trials with respect to..."

Clinical • IO biomarker • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Pediatrics • FLT3

CaDAnCe-302, a phase 3, open-label, randomized study of BGB-16673 compared with idelalisib + rituximab (R), bendamustine + R, or venetoclax + R re-treatment in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma previously exposed to both a BTK and BCL2 inhibitor (ASH 2025) - P1/2, P3 | "Secondary endpoints include overall survival, PFS in patients with prior exposure to noncovalent BTK inhibitors by IRC, PFS by INV, overall response rate by IRC and INV, rate of partial response with lymphocytosis or higher by IRC and INV, duration of response by IRC and INV, time to next treatment, and safety/tolerability per National Cancer Institute Common Terminology Criteria for Adverse Events v5.0. Recruitment is ongoing."

Clinical • IO biomarker • P3 data • B Cell Lymphoma • Chronic Lymphocytic Leukemia • Leukemia • Lymphoma • Prolymphocytic Leukemia • Richter's Syndrome • Small Lymphocytic Lymphoma

Real-world outcomes associated with azacitidine and venetoclax in Myelodysplastic Syndromes (ASH 2025) - "Conclusion : Treatment with azacitidine and venetoclax in patients with higher-risk MDS may be helpful to achieve disease control quickly providing benefit in those intending to proceed to SCT. In our population, azacitidine and venetoclax did not provide long term disease control, especially in TP53-mutated disease."

Clinical • Real-world • Real-world evidence • Acute Myelogenous Leukemia • Aplastic Anemia • Febrile Neutropenia • Hematological Malignancies • Infectious Disease • Leukemia • Myelodysplastic Syndrome • Neutropenia • Septic Shock • Thrombocytopenia • TP53

Meta-analysis confirms venetoclax plus decitabine as a frontline game-changer in elderly AML (Acute Myeloid Leukemia) (ASH 2025) - "This meta-analysis provides compelling evidence that VEN + DEC significantly improves remission and survival outcomes in elderly AML patients, with an acceptable safety margin. The VEN 400 mg + DEC regimen appears to offer the most pronounced clinical benefit. These findings support VEN + DEC as a front-line therapeutic option and call for further prospective trials to optimize patient selection and treatment duration"

Retrospective data • Acute Myelogenous Leukemia • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Leukopenia • Neutropenia • Pneumonia • Respiratory Diseases • BCL2

Venetoclax-based salvage therapy achieves high remission rates after 7+3 or low-dose cytarabine (ASH 2025) - "Introduction: In the Brazilian public health system (SUS), salvage chemotherapy for fit patients with relapsed/refractory (R/R) acute myeloid leukemia (AML) after standard 7+3 induction (7 days of cytarabine plus 3 days of an anthracycline) is usually FLAG-IDA (fludarabine, cytarabine, granulocyte colony-stimulating factor [G-CSF], and idarubicin) or MEC (mitoxantrone, etoposide, and cytarabine)...Although the venetoclax–cytarabine (VEN-ARAC) or venetoclax–azacitidine (VEN-AZA) combination is approved as first-line therapy for unfit patients, it is generally not available in SUS... In this real-world study, VEN-based salvage therapy induced rapid and high CR rates after 7+3 or LDAC, with a favorable safety profile, and may serve as a less-toxic bridge to allo-HSCT."

Clinical • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Neutropenia

Azole-adjusted venetoclax-based regimens in unfit AML patients: A real-world brazilian experience from a resource-limited setting (ASH 2025) - "After 2020, unfit patients were treated with Venetoclax-based regimens (n=54), either combined with Azacitidine 75 mg/m²/day SC for 7 days (AZA-VEN) or with low-dose Cytarabine 20 mg/m²/day SC for 10 days (LoDAC-VEN). All patients received, after ramp-up, azole-adjusted dosing of Venetoclax: 100 mg when combined with Voriconazole or 200 mg with Fluconazole... In this real-world study, Venetoclax-based regimens with azole-adjusted dosing showed better outcomes in unfit AML patients compared to LoDAC or BSC, reinforcing the applicability of such regimens in resource-limited settings. While overall survival in our cohort was lower than reported in pivotal trials, likely due to infectious complications and limited access to supportive care, response rates were comparable. These results support broader incorporation of this approach across diverse healthcare systems."

Clinical • Real-world • Real-world evidence • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Neutropenia

Real-world characteristics, treatment modifications, and outcomes for patients with Acute Myeloid Leukemia (AML) receiving hypomethylating agents (HMA) + venetoclax (VEN) as first-line treatment (1L) (ASH 2025) - "Background: Older patients with acute myeloid leukemia (AML), those with multiple comorbidities, and/or poor performance status are generally considered ineligible for intense chemotherapy and are often treated with combination therapy of hypomethylating agents (HMAs) (azacitidine or decitabine) and venetoclax (VEN) as the standard of care. This real-world study showed that 1L combination of HMA+VEN was effective in managing AML patients that are ineligible for intense chemotherapy. However, treatment modifications due to cytopenia were common. The longer observed rwOS is likely reflective of a younger, high-functioning patient population with favorable ELN risk profile, subsequent therapies used (including stem cell transplant), and/or improvements in dose optimization in clinical practice."

Clinical • Real-world • Real-world evidence • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Neutropenia

Real-world outcomes of myelodysplastic syndrome and chronic myelomonocytic leukemia treated with IDH1 and IDH2 inhibitors in the frontline setting (ASH 2025) - "Selective IDH1/2 inhibitors including ivosidenib (IDH1), olutasidenib (IDH1), and enasidenib (IDH2) are currently approved for IDH1/2-mutated (mIDH1/2) relapsed/refractory (r/r) acute myeloid leukemia; ivosidenib is also approved for mIDH1 r/r MDS based on clinical benefit observed in 18 patients on trial AG120-C-001...Patients previously treated with venetoclax (VEN) or a hypomethylating agent (HMA) were excluded... This study highlights safety and efficacy of IDH inhibitors, particularly among older adults with treatment-naïve MDS or CMML. Nearly half of our cohort were adults >80 years, a group often underrepresented in pivotal clinical trials. The overall response rate (CR + CRl + CRh) was 88.9% among 9 patients with BME; 50% of the entire cohort achieved PB-CR and median OS was 26 months."

Clinical • Real-world • Real-world evidence • Acute Myelogenous Leukemia • Chronic Myelomonocytic Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Neutropenia • IDH1 • IDH2

Utilization patterns of venetoclax-based regimens for AML in a community based setting & representative populational analyses (ASH 2025) - "In first line setting, 22 patients (52.3%) received Venetoclax with azacitidine, 17 patients 40.1% received decitabine, 2 patients (4.8%) with cladribine and cytarabine, and 2 patients (4.8%) received Venetoclax alone...6 patients (40%) received azacitidine with venetcloax, 6 patients (40%) received decitabine, 1 patient (6.7%) received cytarabine, 1 patient (6.7%) received enasidenib, and one patient (6.7%) received nelarabine, cyclophosphamide, and cytarabine... The median age at diagnosis was 64 years (range 21-86). 47% patients were female gender. 24.5% of patients were Black or African-American, 71.4% were White, 1% were Asian, and 3.1% were more than one race."

Clinical • Acute Myelogenous Leukemia • Febrile Neutropenia • Hepatology • Liver Failure • Neutropenia • Renal Disease • CEBPA • DDX41 • NPM1 • TP53

Evaluation of psychosocial impact of myelodysplastic syndromes evaluation by self report (ASH 2025) - P | "Eight (29.6%) were currently on treatment including DNMTi, erythropoietin, venetoclax, and luspatercept. These data also provide valuable feedback on participation in clinical trials and a host of unmet needs in health care delivery. This information can help health care professionals offer tailored support and planning of future intervention trials to improve clinical outcomes, as well as to help patients cope more effectively with their condition."

Acute Myelogenous Leukemia • CNS Disorders • Depression • Erectile Dysfunction • Hematological Malignancies • Infectious Disease • Mood Disorders • Myelodysplastic Syndrome • Post-traumatic Stress Disorder

Validation of the ELN2024 less-intensive prognostic stratification in newly diagnosed AML patients receiving venetoclax-azacitidine: A real-world study from China (ASH 2025) - "In this real-world Chinese cohort, ELN 2024 Less-Intensive stratification clearly separated survival outcomes and outperformed ELN 2022 in VA-treated AML. MRD negativity remained a robust predictor of favorable RFS, and PTPN11 mutations were associated with early relapse. Larger multicenter studies are warranted."

Clinical • Real-world • Real-world evidence • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • PTPN11

Ixazomib combined with daratumumab-based regimens as first-line therapy for transplant-ineligible patients with newly diagnosed multiple myeloma: A real-world historical database analysis from China (ASH 2025) - P2 | "The DI-based regimens included DICd (C: cyclophosphamide; d: dexamethasone) plus vinorelbine (VDS), DId plus VDS, DId plus denosumab, DId plus venetoclax (VEN), DIPd (P: pomalidomide), DIR (R: lenalidomide), and DIRd plus VEN. Conclusion The DI-based regimen, as an initial treatment option for transplant-ineligible NDMM patients, demonstrates efficacy comparable to that observed in previous prospective randomized controlled trials (RCTs) (NCT03012880, NTR6297, ORR: 71–96%). This real-world study conducted in China further supports the promising efficacy and acceptable safety profile of the ixazomib plus daratumumab-based regimen as a first-line treatment for transplant-ineligible NDMM patients in routine clinical practice, including among elderly patients with multiple comorbidities."

Clinical • Real-world • Real-world evidence • Cardiovascular • CNS Disorders • Diabetes • Hematological Disorders • Hematological Malignancies • Hepatology • Hypertension • Metabolic Disorders • Multiple Myeloma • Nephrology • Renal Disease • Transplantation • Vascular Neurology

Transfusion burden across hematologic and solid tumors: A real-world comparative study in AML, multiple myeloma, lung cancer, and melanoma (ASH 2025) - "In parallel, patients with lung cancer or melanoma receiving immune checkpoint inhibitors (ICIs)—nivolumab or pembrolizumab—were followed for 30 days, reflecting delayed hematologic effects...The AML transfusion rate exceeds that seen in phase 3 venetoclax trials, suggesting a greater real-world demand for hematologic support...Such tools could inform real-time transfusion protocols, trigger-based monitoring, or risk-adapted care pathways—particularly in settings with constrained supportive care resources. Future directions include integrating transfusion need into clinical risk models, exploring its role in treatment response prediction, and tailoring supportive care strategies accordingly."

Clinical • IO biomarker • Real-world • Real-world evidence • Acute Myelogenous Leukemia • Hematological Malignancies • Infectious Disease • Leukemia • Lung Cancer • Melanoma • Multiple Myeloma • Neutropenia • Oncology • Solid Tumor

National practice patterns and preferences in the use of fixed-duration vs. treat-to-progression therapies for CLL (ASH 2025) - "In the R/R setting, fixed-duration preferences included venetoclax plus rituximab (39%) and venetoclax plus obinutuzumab (34%)...Among TTP strategies, first-line use of acalabrutinib (56%) and zanubrutinib (52%) was prominent in the survey, aligning with claims data that showed both agents as the most prescribed TTP therapies (28% each)... This data highlighted evolving practice patterns in the management of CLL and revealed variation in treatment preferences among academic and community-based clinicians and between survey and claims data. While adoption of genetic testing and newer therapeutic options appears high, clinicians face ongoing challenges in selecting and implementing appropriate regimens, particularly when balancing patient-centered factors with clinical efficacy and operational realities. Both fixed-duration and TTP strategies offer distinct advantages and limitations."

IO biomarker • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • IGH • TP53

Improved survival in chronic lymphocytic leukemia over two decades: A SEER-based population analysis (2000–2021) (ASH 2025) - "Over the past twenty years, there has been a marked evolution in the landscape of treatment modalities, typified by the incorporation of chemoimmunotherapy in the early 2000s, followed by the advent of targeted therapeutic agents, including Bruton tyrosine kinase (BTK) inhibitors (ibrutinib, acalabrutinib) and BCL2 inhibitors (venetoclax) commencing in the year 2013. Among individuals diagnosed with Chronic Lymphocytic Leukemia (CLL) from the year 2000 to 2021, relative survival rates exhibited significant enhancement across all assessed temporal intervals: 1-year: 85.9% 2-year: 81.2% 5-year: 75.4% - Sex disparities: Female patients demonstrated a superior 5-year survival rate (77.3%) in comparison to their male counterparts (73.5%). - Age disparities: Patients below the age of 65 exhibited a 5-year survival rate exceeding 80%, Whereas patients aged 65 years and older experienced survival rates below 70% prior to the year 2010, yet this figure improved to over 74%..."

Clinical • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia

Real-world treatment utilization, sequencing, and outcomes in Mantle Cell Lymphoma: Emerging treatment patterns in the United States (ASH 2025) - "Treatment regimens were categorized into 7 mutually exclusive groups: bendamustine (B)-based chemotherapy, R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone, with or without cytarabine), Bruton tyrosine kinase inhibitors (BTKi; covalent: zanubrutinib, acalabrutinib, ibrutinib, and non-covalent: pirtobrutinib), bortezomib (bort)-based, venetoclax (ven)-based, intensive chemotherapy (high-dose cytarabine, HyperCVAD (hyperfractionated cyclophosphamide, vincristine, adriamycin, and dexamethasone, etc.), and other regimens (CAR-T or others). However, chemotherapy and/or immunotherapy were associated with the highest HCRU while BTKi were associated with the lowest HCRU. Notably, more than half of patients previously treated with BTKi and anti-CD20 therapies were subsequently treated with another covalent BTKi or a non-covalent BTKi, while approximately one-third received chemotherapy and/or immunotherapy, further emphasizing the need for novel..."

Clinical • HEOR • Real-world • Real-world evidence • B Cell Non-Hodgkin Lymphoma • Chronic Lymphocytic Leukemia • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma