Venclexta (venetoclax) / Roche, AbbVie - LARVOL DELTA

Azacitidine and Venetoclax in Previously Untreated Acute Myeloid Leukemia. (PubMed, N Engl J Med) - P3 | "The incidence of febrile neutropenia was higher in the venetoclax-azacitidine group than in the control group. (Funded by AbbVie and Genentech; VIALE-A ClinicalTrials.gov number, NCT02993523.)."

Journal • P3 data • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Neutropenia • Oncology • Thrombocytopenia

Olutasidenib (FT-2102) induces durable complete remissions in patients with relapsed or refractory IDH1-mutated AML. (PubMed, Blood Adv) - P1/2 | "Response rates were similar in patients who had and who had not received prior venetoclax. The observed efficacy represents a therapeutic advance in this molecularly defined, poor-prognosis patient population with mIDH1 R/R AML. This trial is registered at www.clinicaltrials.gov as NCT02719574."

Journal • Acute Myelogenous Leukemia • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Leukemia • Neutropenia • Oncology • Thrombocytopenia • IDH1

Menin inhibition with revumenib for NPM1-mutated relapsed or refractory acute myeloid leukemia: the AUGMENT-101 study. (PubMed, Blood) - P1/2 | "The protocol-defined efficacy-evaluable population for the primary analysis included 64 adult patients (≥3 prior lines of therapy, 35.9%; prior venetoclax, 75.0%). The safety profile of revumenib was consistent with previously reported results. This trial was registered at www.clinicaltrials.gov as NCT04065399."

Journal • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • Transplantation • KMT2A • NPM1

Azacitidine, Venetoclax, and Revumenib for Newly Diagnosed NPM1-Mutated or KMT2A-Rearranged AML. (PubMed, J Clin Oncol) - P1/2 | "In older adults newly diagnosed with NPM1m or KMT2Ar AML, the combination of azacitidine, venetoclax, and revumenib was able to be safely administered with high rates of CR and clinical activity."

Journal • Acute Myelogenous Leukemia • Hematological Disorders • KMT2A • NPM1

The All-Oral Combination of Revumenib, Decitabine and Venetoclax for Relapsed or Refractory Acute Myeloid Leukemia (SAVE). (PubMed, J Clin Oncol) - "This combination was associated with high response rates and durable remissions, with an acceptable safety, in heavily pretreated patients with AML harboring alterations susceptible to menin inhibition."

IO biomarker • Journal • Acute Myelogenous Leukemia • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Neutropenia • Oncology • Respiratory Diseases • Thrombocytopenia • KMT2A • NPM1 • NUP98

OPTI-AML: PROSPECTIVE RANDOMIZED PHASE 2 TRIAL OF 28 VERSUS 14 DAY SCHEDULE OF VENETOCLAX AND AZACITIDINE FOR 2 CYCLES IN NEWLY DIAGNOSED GENOMICALLY AGNOSTIC ACUTE MYELOID LEUKEMIA PATIENTS ≥60 YEARS (EHA 2026) - P1/2 | "Our study demonstrates the challenges in delivering continuous AV28 per label, however AV14 appears to not be equivalent to AV28 for all genomic subgroups given the heterogeneous nature of AML. Development of aza/ven-based triplet regimens warrants further study to optimize ven duration in molecularly defined subsets."

Clinical • P2 data • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • IDH1 • IDH2 • KRAS • NPM1 • TP53

Long-Term Outcomes of Azacitidine, Venetoclax and Gilteritinib in Newly Diagnosed FLT3-Mutated AML. (PubMed, Blood Adv) - P1/2 | "Randomized studies comparing this regimen to standard of care approaches are warranted. This trial is registered at www.clinicaltrials.gov #NCT04140487."

Journal • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Disorders • Transplantation • FLT3

Targeting CD38 with bispecific antibody XmAb 18968 in patients with relapsed/refractory acute myeloid leukemia and T-cell acute lymphoblastic leukemia. (PubMed, Leukemia) - P1 | "Prior lines of therapy (median 3, range 1-8) included venetoclax (77.3%), allogeneic HCT (22.7%), CD7 CAR-T cell therapy and daratumumab (11.1%). Median OS was 8.5 months in AML and 8.7 months in T-ALL. XmAb18968 is safe and tolerable with encouraging preliminary efficacy, supporting further investigation of CD38 targeting therapies in this setting (NCT05038644)."

Journal • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Neutropenia • Oncology • T Acute Lymphoblastic Leukemia • T-cell Acute Lymphoblastic Lymphoma • Thrombocytopenia • CD7

First-line ibrutinib plus venetoclax for non-blastoid mantle cell lymphoma in patients ≥65 years or with TP53 mutations. (PubMed, Blood) - P3 | "First-line ibrutinib plus venetoclax showed promising efficacy, with high CR rates and durable remissions, in patients with previously untreated non-blastoid MCL and may be an option for patients ≥65 years or patients of any age with TP53m. NCT03112174."

Journal • Fatigue • Hematological Disorders • Hematological Malignancies • Infectious Disease • Lymphoma • Mantle Cell Lymphoma • Neutropenia • Novel Coronavirus Disease • Oncology • TP53

Treatment Naive GPRC5D Negative Multiple Myeloma With t(11;14) (IMS 2026) - P1 | "Clinical validation was performed in 32 RRMM patients enrolled in two anti-GPRC5D CART trials (NCT04555551, NCT05431608) and 117 patients treated with Talquetamab...As additional validation, in the Talquetamab cohort (n=117), patients with t(11;14) and prior Venetoclax sensitivity showed no GPRC5D expression and primary refractoriness to anti-GPRC5D... This study identifies a strong association of GPRC5D negativity with a t(11;14), B-cell-like profile, and genomically indolent myeloma subgroup, potentially conferring refractoriness to anti-GPRC5D therapy. As this group accounts for 10% of NDMM, and GPRC5D protein measurement can be performed by IHC, this represents a feasible and accessible biomarker for immunotherapy selection in myeloma. Importantly, these patients usually have a genomically indolent profile and are particularly sensitive to anti-BCMA therapies (Maura et al."

IO biomarker • Hematological Malignancies • Multiple Myeloma • CD2 • GPRC5D • TP53

Dosing decitabine and venetoclax for terminal differentiation to improve outcomes in TP53 mutant MDS and AML. (ASCO 2025) - P2 | "Venetoclax (Ven) added to the hypomethylating agents (HMA) of Decitabine or Azacitidine is the current standard of care for elderly patients with AML and is frequently used in high-risk MDS (HR-MDS). In this cohort, of elderly patients with poor risk TP53 mutated MDS and AML the use of a non-cytotoxic dosing schedule of Decitabine and Ven resulted in over half the patients achieving a CR and transfusion independence. The median OS of 11.3 months compares favorably to currently approved cytotoxic dosing of HMA/Ven."

Acute Myelogenous Leukemia • Myelodysplastic Syndrome • TP53

Monotherapy update from Phase 1 portion in Phase1/2 trial of the menin-MLL inhibitor enzomenib (DSP-5336) in patients with relapsed or refractory acute leukemia (ASH 2025) - P1/2 | "N=108 (93.1%) had AML and med prior regimen was 2 (1-9); 36 pts (31.0 %) had priorallogeneic stem cell transplant, 86 pts (74.1%) prior venetoclax...DSwas manageable with brief treatment interruption, corticosteroids and hydroxyurea as needed, with nodeaths, study discontinuations, or dose reductions due to DS... ENZO has been well tolerated with no DLTs in 116 pts. ENZO has low lipophilicity and highclearance, leading to a short half-life and has demonstrated a wide therapeutic window. This may allowdosing to be tailored to the specific biology of different AML subtypes."

Clinical • Monotherapy • P1/2 data • Central Nervous System Leukemia • Hematological Malignancies • Leukemia • HOXA9 • KMT2A • MEIS1 • NPM1 • NUP98 • TP53

Cases and Conversations: Sequencing Strategies in Relapsed and Refractory CLL (ASH 2026) - "Pivotal phase 3 readouts — AMPLIFY (acalabrutinib + venetoclax ± obinutuzumab), CLL17, BRUIN CLL-313/-314 (pirtobrutinib), CELESTIAL-TN (sonrotoclax + zanubrutinib), and MAJIC — have reshaped both the treatment armamentarium and the decision framework around fixed-duration vs continuous therapy. Real-world data show persistent gaps in molecular testing, treatment selection, and toxicity management. This Medical Crossfire® session uses focused didactic primers paired with moderated expert debate to examine the frontline decision points clinicians face every day, with attention to molecular testing, fixed-duration vs continuous therapy, MRD-guided approaches, and proactive AE management."

Clinical • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia

Announcement of Awards: William Dameshek Prize, Janet Rowley Basic Science Medal, and Helen M. Ranney Clinical and Translational Science Medal (ASH 2026) - "His research identified the mechanism of action for thalidomide, lenalidomide, and related molecules for multiple myeloma and a subtype of myelodysplastic syndromes. Building upon this work, he codeveloped and led clinical trials on BH3 mimetics, including the first in-human clinical trial of venetoclax and first venetoclax combination trials for chronic lymphocytic leukemia and lymphoma. His pioneering research established a novel class of targeted therapies, BCL2 inhibitors, which have fundamentally reshaped the treatment landscape for patients with hematologic malignancies."

Clinical • First-in-human • IO biomarker • Chronic Lymphocytic Leukemia • Genetic Disorders • Hematological Malignancies • Leukemia • Lymphoma • Multiple Myeloma • Myelodysplastic Syndrome • Sickle Cell Disease • Targeted Protein Degradation

Ernest Beutler Lecture and Prize (ASH 2026) - "Suzanne Cory, PhD, of the Walter and Eliza Hall institute of Medical Research in Melbourne, Australia, will provide a historical overview of the molecular biology of apoptosis and describe how this ultimately led to the development of the BH3 mimetic venetoclax, a highly specific BCL2 inhibitor, which was initially created as a treatment for chronic lymphocytic leukemia. Marina Konopleva, MD, PhD, of the Albert Einstein College of Medicine, will summarize translational work that credentialed BCL2 as a therapeutic target in acute myeloid leukemia (AML), as well as describe the rapidly changing landscape in the clinical care of AML patients in which BCL2 inhibition is incorporated into a multitude of chemotherapy and targeted therapy combinations."

Acute Myelogenous Leukemia • Chronic Lymphocytic Leukemia • Follicular Lymphoma • Hematological Malignancies • Leukemia • Lymphoma

Are We There Yet? Improving Outcomes in MDS (ASH 2026) - "She will highlight recent findings from the phase III VERONA trial and discuss the role of venetoclax in clinical practice in light of these results. Dr. Maximilian Stahl will examine the role of targeted therapies in MDS and clonal cytopenias of undetermined significance (CCUS), identifying patient subsets most likely to benefit and summarizing ongoing efforts to integrate targeted approaches into clinical care."

Acute Myelogenous Leukemia • Aplastic Anemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome

Chronic Lymphocytic Leukemia - From Clonal Evolution to Novel Therapies (ASH 2026) - "Finally, Dr. Coombs will focus on late-line CLL, including patients failed by covalent BTK inhibitors and venetoclax and Richter's transformation."

Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Richter's Syndrome

Targeted Therapies for AML: Bulls Eye! (ASH 2026) - "Lastly, the impactful development and future directions of novel combinations of menin inhibitors with frontline azacitidine/venetoclax and intensive chemotherapy for newly diagnosed AML patients will be reviewed and summarized. Kadia will review future directions in the treatment of AML, including the use of new combination strategies: new chemotherapy backbones, new targeted therapy combinations. Also, will touch on mechanisms of resistance to currently available therapies and the development of next generation therapies to address these mechanisms of resistance."

Acute Myelogenous Leukemia

The Golden Era of ALL Management: Rapid Advances Across the Age Spectrum (ASH 2026) - "Further augmentations of B-ALL chemotherapy with venetoclax, inotuzumab, tyrosine kinase inhibitors, and other agents are being tested and may improve outcomes in specific patient subsets. Emphasis will be placed on integrating disease biology, fitness, antigen expression, and MRD kinetics to guide sequencing of inotuzumab ozogamicin, blinatumomab, TKI-based therapy for Ph-positive disease, CAR T-cell therapy, and alloHCT. Key clinical challenges include discordant flow versus NGS MRD results, persistent MRD after sequential immunotherapy, antigen escape, and individualized escalation strategies aimed at durable MRD-negative remission with preserved quality of life."

IO biomarker • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • T Acute Lymphoblastic Leukemia

Greasy Situations: Unraveling Lipid-Mediated Therapy Resistance (ASH 2026) - "Dr. Mala Shanmugam will elucidate the mechanistic basis of how fatty acids alter BCL-2 dependence and sensitivity to BCL-2 targeting agents like venetoclax in multiple myeloma."

IO biomarker • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Multiple Myeloma • Obesity • BCL2

NCI-2018-01589: Liposome-encapsulated Daunorubicin-Cytarabine and Venetoclax in Treating Participants With Relapsed, Refractory or Untreated Acute Myeloid Leukemia (clinicaltrials.gov) - P2 | N=72 | Recruiting | Sponsor: M.D. Anderson Cancer Center | N=52 ➔ 72

Enrollment change • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Combination Targeted Therapy in Relapsed Diffuse Large B-Cell Lymphoma. (PubMed, N Engl J Med) - P1/2 | "Treatment with ViPOR was associated with durable remissions in patients with specific molecular DLBCL subtypes and was associated with mainly reversible adverse events. (Funded by the Intramural Research Program of the National Cancer Institute and the National Center for Advancing Translational Sciences of the National Institutes of Health and others; ClinicalTrials.gov number, NCT03223610.)."

IO biomarker • Journal • P1 data • P2 data • Cerebral Hemorrhage • CNS Disorders • Diffuse Large B Cell Lymphoma • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Indolent Lymphoma • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Thrombocytopenia • BCL2 • BCL6 • MYC

PRELIMINARY RESULTS OF THE ONGOING MULTICENTER, PHASE 2 STUDY OF RETREATMENT WITH VENETOCLAX PLUS OBINUTUZUMAB (ReVenG) IN PATIENTS WITH RECURRENT CLL (ICML 2025) - P2 | "In this interim analysis of the initial pts on ReVenG, efficacy was observed, and the safety of Ven-Obi in these relapsed pts was similar to prior studies. The study is actively accruing, and more pts with longer follow-up are needed to more completely assess Ven-Obi re-treatment."

Clinical • IO biomarker • P2 data • Chronic Lymphocytic Leukemia • Lymphoma • BCL2

CELESTIAL-TNCLL: An ongoing, open-label, multiregional, phase 3 study of sonrotoclax (BGB-11417) + zanubrutinib vs venetoclax + obinutuzumab for treatment-naïve (TN) CLL. (ASCO 2024) - P3 | "Background: The combination of venetoclax (ven), the first-generation BCL2 inhibitor, and ibrutinib, a BTK inhibitor, has demonstrated efficacy in patients with CLL (Wierda et al. Other secondary endpoints include PFS as assessed by investigator (INV); CRR by INV; rate of uMRD4 based on flow cytometry; overall response rate by IRC and INV; duration of response by IRC and INV; patient-reported outcomes; and safety and tolerability. Recruitment is ongoing."

Clinical • IO biomarker • P3 data • Chronic Lymphocytic Leukemia • Hematological Disorders • Neutropenia • TP53

Preliminary Safety and Efficacy from a Multicenter, Investigator-Initiated Phase II Study in Untreated TP53 Mutant Mantle Cell Lymphoma with Zanubrutinib, Obinutuzumab, and Venetoclax (BOVen) (ASH 2021) - P2 | "Obinutuzumab, ibrutinib, and venetoclax has been shown to be well tolerated and associated with high response rates in relapsed and untreated MCL patients (Le Gouill Blood 2021). BOVen was well tolerated in untreated TP53 mutant MCL. The preliminary efficacy is promising in this high-risk subset of MCL, however, follow-up is limited. Updated response data, including minimal residual disease assessment using a next-generation immunosequencing (IS) assay, will be presented at the meeting."

Clinical • IO biomarker • P2 data • Hematological Disorders • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Neutropenia • Oncology • Thrombocytopenia • CARD11 • SMARCA4 • TP53