Venclexta (venetoclax) / Roche, AbbVie - LARVOL DELTA

Outcomes of Pharmacist-Driven Venetoclax Appeals in Acute Myeloid Leukemia (HOPA 2026) - "Findings may support pharmacist advocacy, streamline institutional workflows, and inform payer policy to reduce barriers for patients with AML requiring venetoclax."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia

Treatment Outcomes in Relapsed/Refractory KMT2A-Rearranged Acute Myeloid Leukemia (HOPA 2026) - "Furthermore, menin inhibitors, such as revumenib, have recently also shown efficacy in the phase I/II trials.(2) However, several of these studies have small sample sizes and/or do not have a comparator arm, making it difficult to make definitive conclusions regarding the comparative effectiveness of these regimens...OBJECTIVE To compare efficacy and safety between intensive chemotherapy and hypomethylating agent-venetoclax regimens in adult patients with R/R KMT2-rearranged AML c. METHODS This study is a single-center retrospective cohort study...e. CONCLUSIONS Results pending."

Clinical • Acute Myelogenous Leukemia • Febrile Neutropenia • Gene Therapies • Hematological Disorders • Hematological Malignancies • Leukemia • Neutropenia • KMT2A

Assessing the Safety and Efficacy of Cladribine, Low-Dose Cytarabine Plus Venetoclax in Patients with Newly Diagnosed, and Relapsed/Refractory Acute Myeloid Leukemia (HOPA 2026) - "Despite this, complete remission rates with azacitidine and venetoclax remain modest at approximately 36.7%2, underscoring the ongoing need for additional effective and tolerable treatment options. Conclusion to be presented upon completion of final data analysis."

Clinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia

Retrospective Real-World Evaluation of Treatment Strategies and Outcomes in TP53-Mutated Acute Myeloid Leukemia (HOPA 2026) - "Background/Rationale: TP53-mutated acute myeloid leukemia (TP53m AML), which accounts for 5-15% of de novo AML, about 18% of secondary AML, and up to 30% of therapy-related AML, represents a poor-risk subset with an overall survival of approximately 6 months independent of age and fitness.1,2 Treatment strategies for these patients remain unclear, as TP53 mutations confer resistance to most standard-of-care approaches such as intensive chemotherapy and venetoclax with hypomethylating agents (HMAs)... Conclusions pending."

HEOR • Real-world • Real-world evidence • Retrospective data • Tumor mutational burden • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • TMB • TP53

Real-World Effectiveness of Intensive Venetoclax plus Purine Analog-Based Induction (FLAG-IDA-Ven or CLIA-Ven) for Newly Diagnosed Acute Myeloid Leukemia (HOPA 2026) - "Background/rationale: Cytarabine plus daunorubicin (7+3) remains a standard induction regimen for adults with newly diagnosed acute myeloid leukemia (AML). research in progress"

Clinical • Real-world • Real-world effectiveness • Real-world evidence • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia

A retrospective cohort study of outcomes of CLL/SLL patients initiating venetoclax-based treatment following covalent BTKi therapy with or without bridging therapy (HOPA 2026) - "Discussion/Conclusion Results pending. This study aims to generate real-world evidence on the clinical impact of BTKi bridging during venetoclax initiation and may inform future treatment sequencing strategies in CLL/SLL."

Retrospective data • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Small Lymphocytic Lymphoma

Clinical and Molecular Characteristics of Long-Term Responders to HMA-Venetoclax Therapy in Acute Myeloid Leukemia: A Retrospective Analysis (HOPA 2026) - "Background : The combination of hypomethylating agents (HMAs), azacitidine or decitabine, and venetoclax has become a standard treatment for older adults or patients with comorbidities diagnosed with acute myeloid leukemia (AML) deemed unfit for intensive chemotherapy.1 While the VIALE-A trial reports a median overall survival (OS) of 14.7 months for those treated with azacitidine-venetoclax, a subset of patients demonstrates prolonged responses beyond two years.2 Objective: This study aims to identify clinical and molecular characteristics associated with durable remission (≥24 months) in patients receiving HMA-venetoclax for AML. Patients aged 18 years and older who received ≥ 24 months of HMA-venetoclax for AML were eligible for the study. Results : Results pending Conclusion : Conclusion pending"

Retrospective data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia

Phase 3 Study to Evaluate Efficacy and Safety of Pemivibart, an IgG1 Monoclonal Antibody, for the Prevention of COVID-19 (CANOPY): Subset Analysis of Participants With Chronic Lymphocytic Leukemia (HOPA 2026) - P3 | "In all, 9 (31%) participants were receiving antineoplastic agents, including venetoclax (n=3), acalabrutinib (n=2), and ibrutinib (n=2). Pemivibart was well tolerated in a subset of adults with CLL. None of the study patients had COVID-19 in the 6 months after the administration of pemivibart."

Clinical • P3 data • Chronic Lymphocytic Leukemia • Hematological Malignancies • Infectious Disease • Leukemia • Novel Coronavirus Disease • Respiratory Diseases

Dual FLT3/BRAF inhibitor PHI3 overcomes RAS-driven resistance in FLT3-mutant AML (AACR 2026) - "Background: FLT3 mutations define a high-risk subset of AML, and FLT3 inhibitors are routinely used in combination with induction chemotherapy in fit patients, and with a low-intensity HMA/Venetoclax backbone in older patients...RAS mutations emerge in ~20% of patients who progress on gilteritinib or other FLT3 inhibitors, driving sustained MAPK activation and therapy resistance... PHI3 is a potent dual BRAF/FLT3 inhibitor that effectively suppresses MAPK pathway reactivation and overcomes RAS-driven resistance to FLT3 inhibitors in AML. Its strong in vivo efficacy and tolerability positions PHI3 as a promising therapeutic candidate. These findings provide a clear mechanistic and translational rationale for advancing dual FLT3/BRAF targeting in patients with FLT3-mutant and FLT3/RAS co-mutant AML."

Acute Myelogenous Leukemia • Oncology • FLT3 • KRAS • NRAS

Discovery of first-in-class YTHDC1 small molecule inhibitors for the treatment of MYC-driven cancers (AACR 2026) - "Moreover, YTHDC1 inhibition shows pronounced synergy with standard of care agents such as venetoclax in AML. Collectively, these findings establish YTHDC1 as a tractable therapeutic target for MYC-driven malignancies."

Acute Myelogenous Leukemia • Genito-urinary Cancer • Genitourinary Neuroendocrine Carcinoma • Hematological Malignancies • Leukemia • Lung Cancer • Oncology • Prostate Cancer • Small Cell Lung Cancer • Solid Tumor • YTHDC1

Optimizing the linker of venetoclax-artemisinin conjugates to improve water solubility and antileukemia effects (AACR 2026) - "These modifications led to further increased aqueous solubility and colony-forming inhibitory activity. These novel conjugates represent promising next-generation venetoclax derivatives capable of overcoming resistance."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • BCL2L1 • MCL1

Eflornithine and venetoclax combination therapy: Targeting senescence to induce apoptosis in neuroblastoma (AACR 2026) - "Together, these findings establish a novel mechanistically informed combinatorial strategy in which polyamine depletion converts senescent tumor cells into apoptotically vulnerable targets, offering a promising therapeutic avenue for HRNB. Ongoing in vivo studies will determine the translational potential of eflornithine + venetoclax as a rational senescence-targeting regimen."

Combination therapy • IO biomarker • Hematological Malignancies • Neuroblastoma • Oncology • Solid Tumor • CASP3 • CDKN1A • GLS1 • IFNG • IL1B • IL6 • MCL1

BGB-21447, a next generation Bcl-2 inhibitor, shows high potential in Bcl-2 overexpressing B cell non-Hodgkin lymphomas (NHL) cancers in preclinical studies (AACR 2026) - "In this study, we evaluate the potential of BGB-21447, a next-generation Bcl-2 inhibitor structurally distinct from sonrotoclax (BGB-11417), mainly in DLBCL/B-NHL via preclinical studies. Cell viability was assessed by CTG assay in vitro. These findings indicate that BGB-21447 is a Bcl-2 inhibitor with substantially greater potency than venetoclax and strong potential in indications such as DLBCL where venetoclax has suboptimal efficacy. Clinical trials are needed to validate these results."

IO biomarker • Preclinical • B Cell Non-Hodgkin Lymphoma • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology

A novel CD33 and TRAIL-R2 targeting bispecific antibody to treat relapsed/refractory acute myeloid leukemia (AACR 2026) - "Furthermore, current therapies such as hypomethylating agents (HMA) and venetoclax (Ven) fail in patients with TP53 mutations...Safety was assessed ex vivo using human liver microtissue and immune cells.TRIO-863 showed potent CD33-dependent killing of AML cells including high risk TP53-mutant and drug-resistant models, with over 3700-fold greater potency than Mylotarg...This approach addresses major limitations of current treatments. Clinical trials are planned for relapsed/refractory AML, including TP53-mutant and drug-resistant cases."

Bispecific • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CD33 • CD34 • MCL1 • TNFRSF10B

Antitumor synergy of AOH1996 and next-generation caPCNA Inhibitors in combination with targeted and chemotherapeutic agents (AACR 2026) - " Both AOH1996 and its next-generation analogs demonstrated synergy with some DNA-damaging and repair inhibiting agents such as cisplatin. AOH1996 and its next-generation analogs exhibit potent synergistic activity with targeted therapies and DNA repair inhibitors, supporting PCNA inhibition as a promising strategy to enhance therapeutic efficacy and overcome resistance. These findings provide a preclinical rationale for clinical development of AOH1996 combination regimens, as well as continued optimization of caPCNA-targeting analogs with superior potency and tolerability."

Combination therapy • Neuroblastoma • Oncology • Solid Tumor • PCNA

Actimab-A, a CD33-targeted actinium-225 radioconjugate, drives mutation-agnostic anti-leukemic activity and synergizes with standard therapies in AML through transcriptional reprogramming (AACR 2026) - "Clinical studies have shown encouraging responses when combined with CLAG-M chemotherapy in relapsed/refractory AML, including in patients with TP53 mutations or venetoclax resistance...To explore mechanisms of synergy, AML cell lines harboring common mutations (FLT3, KMT2Ar: MV-4-11, MOLM-13 cells, NPM1c: OCI-AML3, and mutant TP53: Kasumi-1, HL-60 cells) were treated for 24 hours with standard-of-care (SOC) therapies: FLT3 inhibitors (gilteritinib, quizartinib), menin inhibitors (revumenib, ziftomenib) or azacitidine alone or in combination with lintuzumab-Ac225... Lintuzumab-Ac225 shows broad mutation-independent anti-leukemic activity in AML cell lines and primary AML patient samples. When combined with standard therapies, it drives complementary transcriptional programs that enhance depth and durability of response. Together, these findings support the clinical evaluation of lintuzumab-Ac225-based combinations as a strategy to overcome resistance and enhance..."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CD33 • FLT3 • KMT2A • MYC • NPM1

Exploiting MYC Oncogenic Stress for Therapeutic Benefit in Lymphoma (AACR 2026) - "Genome-wide CRISPR screens sorted on viable, non-apoptotic cells treated with venetoclax +/- MYC degradation demonstrated that the strongest genetic regulators of differential response to venetoclax were DNA replication and damage and cell cycle genes. These results indicated that disruption of these pathways could synergize with high MYC to promote sensitivity of DHIT-GCB cells to venetoclax.Finally, functional assays with clinically available targeted therapies perturbing DNA damage and cell cycle highlighted how MYC levels relate to these processes in malignant B-cells and thus modulate response to BCL2 inhibition.These studies may suggest drug combinations strategies that would harness the synergism between MYC and BCL2 in DHIT-GCB, and hopefully improve therapeutic outcomes for these DLBCL patients."

IO biomarker • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • MYC

CLK inhibitor BH-30236 synergizes with venetoclax in anti-leukemia activity via splicing modulation in preclinical AML and CLL models (AACR 2026) - P1 | "This finding is consistent with BH-30236 modulation of leukemia stem cells via regulation of alternative splicing. BH-30236 is currently under clinical investigation, either as a single agent or in combination with venetoclax, in adults with relapsed or refractory AML or higher risk MDS in a Phase 1/1b clinical trial (NCT06501196)."

IO biomarker • Preclinical • Acute Myelogenous Leukemia • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • MCL1

Cuproptosis induction in TP53-mutated acute myeloid leukemia (AACR 2026) - "In contrast, cytarabine, idarubicin, and venetoclax activity was substantially diminished in TP53-deficient cells, consistent with the known resistance of TP53-mutated AML to these standard therapies. Notably, combining low-dose elesclomol with the hypomethylating agent decitabine, which has established clinical efficacy in TP53-mutated AML, produced a synergistic increase in apoptosis in TP53-deficient AML cells.Together, these findings demonstrate that copper ionophores can bypass TP53-associated resistance to AML cell death by activating cuproptosis rather than relying on p53-dependent apoptotic pathways. The robust activity of copper ionophores across diverse TP53-deficient AML models, coupled with the enhanced efficacy observed in combination with decitabine, underscores cuproptosis induction as a promising therapeutic approach for TP53-deficient AML."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • TP53

CD47 blockade induces necroptosis and complements the effects of BCL-2 inhibition in hematologic malignancies (AACR 2026) - "This cell death mechanism has yet been well-characterized, thus warranting investigation to comprehensively unravel the mechanism of CD47 blockade and to facilitate the identification of optimal drug partners for combination therapy. Anti-CD47 monoclonal antibodies (mAb), SRF231, magrolimab, B6H12, were evaluated for cell death mechanisms such as apoptosis, autophagy or necroptosis. Our study unravels a novel cell death mechanism of CD47 blockade through necroptosis, thereby permitting the inclusion of venetoclax-induced apoptosis, a complementary combination worthy of further study against BCL-2 dependent hematologic malignancies in the clinic."

Acute Myelogenous Leukemia • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • ANXA5

Venetoclax enhances radiation-induced anticancer immunity in breast cancer (AACR 2026) - "Collectively, our findings identify both BCL2 and mitophagy as immune checkpoints that suppress RT-induced immune responses. These pathways represent actionable targets for novel therapeutic strategies to overcome immunotherapy resistance not only in ER+ breast cancer, but also in other "cold" tumor types."

IO biomarker • Breast Cancer • Estrogen Receptor Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • ATG7 • ER

Preclinical evaluation of a cardiosafe first-in-class MCL-1 degrader for the treatment of hematological malignancies (AACR 2026) - "Combination with low-dose venetoclax (7.5 mpk) promoted tumor regression at 5 mpk using an intermittent dosing regimen (2 days on/5 days off)...These findings support MCL-1 degradation as a promising therapeutic approach for hematologic malignancies. The compound is advancing through IND/CTA-enabling studies, with a first-in-human Phase 1 trial planned for 2026."

First-in-human • Preclinical • Hematological Malignancies • Leukemia • Lung Cancer • Mantle Cell Lymphoma • Multiple Myeloma • Oncology • Solid Tumor • BCL2 • MCL1 • TNNI3

Cell Avidity: The Next-Gen cell binding assay to understand therapeutic mechanism of action through quantifying cell-cell and cell-protein interaction strength (AACR 2026) - "• Assess the impact of Venetoclax treatment on NK cells, finding improvements to cytoskeleton remodeling and lytic granule polarization, which contributed to a more efficient IS, enhancing NK cell-mediated killing of AML cells... We developed a Cell Avidity platform that enables the characterization and screening of molecular binders and cellular products, including antibodies, small molecules, and cell therapies. Cell Avidity provides comprehensive information on potency, selectivity, sensitivity, and kinetics, offering key insights into the mechanism of action for cell therapies."

Genito-urinary Cancer • Oncology • Pancreatic Adenocarcinoma • Renal Cell Carcinoma • Solid Tumor

Targeting BCL2 pathway to enhance immunogenicity in ALK+ NSCLC (AACR 2026) - "However, this has not been studied in the context of ALK+ NSCLC.We hypothesized that ALK-directed therapy in combination with BH3 mimetics would initiate ICD through the release of DAMPs and increase sensitivity to ALK TKIs. We evaluated the efficacy of ALK TKIs (Lorlatinib, Alectinib) alone and in combination with the BH3 mimetics navitoclax (BCL-2/BCL-xL inhibitor), venetoclax (BCL-2 inhibitor) and s63845 (MCL-1 inhibitor) to induce damage-associated molecular patterns (DAMPs) in ALK+ NSCLC cell lines. ALK+ cancer cell lines exhibited high expression of MCL-1 and BCL-xL proteins, indicating their dependency on BCL-2 family proteins for survival. ALK-directed therapy has the potential to induce immunogenic cell death (ICD) and elicit antitumor immune responses. Combining BH3 mimetics with ALK TKIs can be a promising therapeutic strategy to enhance anti-tumor immunity and overcome ALK TKI resistance in ALK+ NSCLC"

IO biomarker • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • BCL2L1 • CXCL10 • IFNB1

BGB-21447, a next-generation Bcl-2 inhibitor, demonstrates superior potency and overcomes Venetoclax resistance in preclinical models of hematologic malignancies (AACR 2026) - P1 | "At 1.5 mg/kg, BGB-21447 showed superior antitumor efficacy compared to VEN at 15 mg/kg and ABBV-453 (AbbVie's selective Bcl-2 inhibitor) at 1.5 mg/mL. No significant weight loss or laboratory toxicities were observed.In conclusion, BGB-21447 surpasses VEN in potency and mutant coverage, and durably inhibits VEN-resistant tumors at well-tolerated doses in preclinical models. These findings support the ongoing Phase 1 clinical trials (NCT05828589, NCT06756932) evaluating BGB-21447 in B-cell malignancies and metastatic breast cancer."

IO biomarker • Preclinical • Breast Cancer • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor • ANXA5 • BCL2A1 • BCL2L1 • BCL2L2 • CASP3 • CASP7 • MCL1