Zydelig (idelalisib) / Gilead - LARVOL DELTA

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

Patient assistance for drug cost sharing: Highlighting the variability across pharmaceutical manufacturers of specialty oral anticancer medications for blood cancers (ASH 2025) - "Two of the three manufacturers that did not offer a PAP had discontinued their free-drug program (idelalisib and duvelisib) whereas one never had a free drug program (revumenib). All SOAMs for blood cancer have copay assistance programs for commercially insured and nearly all directly provide free-drugs for select individuals. However, eligibility by insurance type, income level, and associated documentation requirements vary considerably across manufacturers. Future work needs to evaluate whether this variability results in inequitable access across SOAM agents within same indication."

Clinical • Drug cost • HEOR • Hematological Malignancies • Oncology • Oral Cancer

Integrating oncofertility: Contraceptive guidance in chronic lymphocytic leukemia (ASH 2025) - "BTK inhibitors (e.g ibrutinib) increase thrombotic risk through platelet dysfunction and coagulopathy and may reduce the efficacy of estrogen-containing contraceptives through CYP3A4 induction. Similarly, BCL-2 inhibitors (e.g venetoclax) increase thrombotic risk, particularly when combined with other platelet-function impairing agents, warranting cautious use of estrogen-based contraceptives...Furthermore, conventional chemotherapy (e.g fludarabine, cyclophosphamide) and some target therapies (e.g idelalisib) also present high thrombosis risk and hepatotoxicity, potentially impairing hormonal contraceptive metabolism...On the other hand, immunotherapy agents (e.g rituximab) demonstrate variable thrombosis risks, especially when used in combination therapies... Contraception in women with chronic lymphocytic leukemia (CLL) presents complex challenges requiring individualized care. As many CLL treatments have gonadotoxic and teratogenic properties, it is imperative to..."

Chronic Lymphocytic Leukemia • Hematological Malignancies • Infectious Disease • Leukemia • Long-acting Reversible Contraceptives • Thrombosis • CYP3A4

PI3Kδ inhibition enhances trametinib efficacy by suppressing feedback-activated PI3K/AKT signaling in PTPN11-mutant JMML (ASH 2025) - "These data collectively support thenotion that MEK inhibition relieves feedback inhibition on RAS, resulting in its hyperactivation anddiversion of signaling through bypass pathways such as PI3K/AKT.To counteract compensatory PI3K/AKT activation under MEK inhibition, we tested Trametinib combinedwith Idelalisib, a selective PI3Kδ inhibitor. This dual blockade strategy provides a mechanistic rationale andpreclinical proof-of-concept for combination therapy in PTPN11-mutant JMML, which is historicallyresistant to single-agent MEK inhibitors. These results support future clinical investigation of MEK andPI3Kδ co-inhibition to improve treatment outcomes in this high-risk JMML subgroup."

Clinical • Chronic Myelomonocytic Leukemia • Hematological Malignancies • Juvenile Myelomonocytic Leukemia • Leukemia • Thrombocytopenia • PIK3CD • PTPN11

A decade of progress: A comparative analysis of real-world survival in chronic lymphocytic leukemia across therapeutic eras (ASH 2025) - "The ECOG E1912 randomized study demonstratedsuperior overall survival of ibrutinib-based therapy compared to chemoimmunotherapy with fludarabine,cyclophosphamide, and rituximab (FCR)...For these cohorts, 5-year all-cause mortality was comparedbetween the pre-2015 and 2015-2020 groups, and 2-year all-cause mortality was compared between thepre-2015 and post-2020 groups.Second, to directly compare treatment effectiveness, patients who received systemic therapy werestratified into two cohorts based on the class of agent received, irrespective of the treatment date:Chemoimmunotherapy (CIT): Regimens including FCR, BR, Fludarabine with Rituximab,Chlorambucil ± Obinutuzumab, and Alemtuzumab-based treatments.Novel Targeted Therapy: Regimens including covalent BTK inhibitors (Ibrutinib, Acalabrutinib,Zanubrutinib), BCL-2 inhibitor Venetoclax (± Rituximab or Obinutuzumab), and PI3K inhibitors(Idelalisib, Duvelisib).For these treatment-regimen cohorts, 10-year outcomes..."

Clinical • Real-world • Real-world evidence • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia

Inhibition of lysine acetyltransferases p300/CBP overcomes BTK inhibitor resistance in a xenograft model of Mantle Cell Lymphoma by suppressing MYC signaling (ASH 2025) - P1/2 | "Thesynergistic effect of p300/CBPi was greater than when combined with PI3K inhibitor (idelalisib) or BCL2inhibitor (venetoclax)...Mean tumor volumes (mm³) at the endpoint were: DMSO, 1314.7; ibrutinib, 949.0; A-485, 1022.8; and combination, 397.2 (all p < 0.001 vs. combination)...No significant weight loss ortoxicity was observed in any treatment group. Western blot analysis of harvested xenograft tumorsshowed that the combination reduced phosphorylation of BTK, AKT, and STAT3, and decreaseddownstream MYC protein expression.Conclusionp300/CBP inhibition overcomes BTKi resistance in MCL primarily by suppressing MYC-driven signaling.These findings provide strong preclinical support for clinical evaluation of BTKi and p300/CBPicombination therapy in patients with BTKi-resistant MCL."

IO biomarker • Preclinical • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • ANXA5 • CCND1 • IL6 • MYC • PLCG2

Integrated single-cell RNA sequencing and TCR profiling identifies immune drivers of severe early toxicity in CLL patients treated with idelalisib (ASH 2025) - "PI3K inhibitors, such as idelalisib and duvelisib, have demonstrated efficacy in relapsed/refractory chroniclymphocytic leukemia (CLL) but severe autoimmune toxicities limit their clinical use. This aligns with prior findings that CD4+ Tcells reprogram metabolism and promote Th17 responses via HIF-1α and GLUT1 in rheumatoid arthritis,an autoimmune disease.Overall, our findings suggest idelalisib-induced toxicity develops in patients with a predisposed immunemicroenvironment with sustained higher clonal diversity and metabolic-immune dysregulation, leading tothe expansion of CD8+ and CD4+ T cell clones with TH17/TH1 polarization, cytotoxicity, and migratoryphenotypes. These insights into PI3Kδ inhibitor-induced toxicity may suggest potential targets to mitigateadverse effects."

Clinical • Chronic Lymphocytic Leukemia • Hematological Malignancies • Immunology • Inflammatory Arthritis • Leukemia • Rheumatoid Arthritis • Rheumatology • Transplant Rejection • ACLY • BACH2 • CD4 • CD8 • CXCR3 • EGR1 • FOXP3 • GZMB • HIF1A • IFNG • IFNGR1 • IL7R • IRF1 • JAK2 • LDHA • MTHFD2 • PIK3CD • PRF1 • RAC2 • SLC2A1 • STAT1 • TBX21 • TMSB4X • ZEB1

Population-Based Registry Data over 15 Years Suggests Comparable Overall Survival for CLL Patients Treated with Chemoimmunotherapy and Targeted Therapies As First-Line Treatments (ASH 2024) - "The first-line treatments with CT included chlorambucil (Chl) 60.8%, fludarabine ± cyclophosphamide (FC) 32.6%, and bendamustine (Ben) 6.6%. CIT included FC/FCM (mitoxantrone) with a CD20 antibody (ab) 52.1%, Ben with a CD20 ab 16.6%, Chl with a CD20 ab 27.2%, alemtuzumab ± CT 2.0%, and other regimens 4.0%. TT included acalabrutinib ± Obinutuzumab (O) 29.7%, ibrutinib ± rituximab (R) 36.4%, venetoclax ± O or ibrutinib 26.1%, idelalisib ± R 3.6%, and zanubrutinib 3.6%...In this population-based registry study, it was shown that only around a third of patients with CLL required treatment, and there was no OS advantage from initiating patients on targeted therapy as a first line compared to chemoimmunotherapy followed by targeted therapy upon relapse. This concept should be validated in prospective trials."

Clinical • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology

Chronic lymphocytic leukemia in routine care in Germany: Changes in standard of care – results from the prospective RUBIN registry (DGHO 2025) - P | "Chemoimmunotherapy (CIT) regimens (rituximab(R)-bendamustine (53.4%), FCR (25.2%) and R-chlorambucil (6.1%)) were by far the most common between 2009 and 2015. In contrast, since 2023, obinutuzumab(O)-venetoclax (31.6%) was the most frequent regimen, followed by the 2nd generation BTKis acalabrutinib (16%) and zanubrutinib (15.5%).Of 516 prospectively documented 2L treatments, 122 (23.6%) started between 2009 and 2013, 98 (19.0%) between 2014 and 2018, and 296 (57.4%) between 2019 and 2024.Change from CIT towards targeted agents was also observed in 2L. R-bendamustine (40.8%) was still the most common regimen 2014 - 2018, followed by ibrutinib (17.3%) and R-idelalisib (8.2%)... The data from RUBIN show that after their approval, novel agents for CLL treatment are rapidly adopted into real-world practice. Current treatment guidelines are reflected, with venetoclax based regimen and 2nd generation BTKis as most frequent regimens. Outcome data over time will also be..."

Clinical • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma

Relative Efficacy of Systemic Treatments for Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia: A Network Meta-Analysis According to 17p Deletion/TP53 Mutations (ASH 2024) - "Ibrutinib was used as reference treatment.Results : Twelve trials involving 4,437 patients and 13 treatment options were included in the meta-analysis : three Bruton tyrosine kinase (BTK) inhibitors (ibrutinib, acalabrutinib, and zanubrutinib), two BTK inhibitors combined with other treatments (ibrutinib plus rituximab plus bendamustine [RB] and ibrutinib plus rituximab), two phosphoinositide 3-kinase (PI3K) inhibitors (idelalisib and duvelisib), three PI3K inhibitors combined with other treatments (idelalisib plus ofatumumab, idelalisib plus RB, idelalisib plus rituximab), three anti-CD20-based treatment (RB, ofatumumab, and rituximab), and one BCL-2 inhibitor (venetoclax plus rituximab). In the 17p deletion/TP53 mutation subgroup, zanubrutinib demonstrated the most favorable efficacy (HR 0.52, 95% CI 0.31-0.88 versus ibrutinib) with the highest SUCRA value (97%). For patients without these mutations, venetoclax plus rituximab was the most effective (HR 0.49, 95% CI..."

IO biomarker • Retrospective data • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • TP53

Financial Toxicity and Quality of Life in Patients Taking Oral Therapy for Hematologic Malignancies (ASH 2023) - "MethodsWe used database query to identify patients at a midwestern, tertiary care, academic medical center who were 18 years or older and were prescribed Enasidenib, Ivosidenib, Venetoclax, Gilteritinib, Midostaurin, Ibrutinib, Acalabrutinib, Imatinib, Nilotinib, Ponatinib, Bosutinib, Duvelisib, or Idelalisib within the past 3 months. Financial stress and hardship were associated with worse satisfaction with QoL and worse experience of SE. Further study should define change in these features over time and interventions to mitigate distress."

Clinical • HEOR • Acute Myelogenous Leukemia • Chronic Lymphocytic Leukemia • CNS Disorders • Depression • Hematological Malignancies • Mood Disorders • Oncology • Oral Cancer • Psychiatry

A Phase 2 Study of Zanubrutinib and Venetoclax (ZV) in Relapsed or Refractory (R/R) Chronic Lymphocytic Leukemia (CLL) (ASH 2024) - P2 | "One pt had prior therapy with ibrutinib and venetoclax (double-exposed), another pt had prior ibrutinib and acalabrutinib which were stopped due to intolerance, and two had prior idelalisib. Conclusions Fixed-duration combination therapy with ZV is active and well-tolerated in R/R CLL, including in pts with previous exposure to targeted agents. This study is actively accruing, and larger numbers of pts with longer follow-up will help further improve our understanding of the potential benefits of this regimen in R/R CLL."

P2 data • Atrial Fibrillation • B Cell Lymphoma • Cardiovascular • Chronic Lymphocytic Leukemia • Febrile Neutropenia • Hematological Disorders • Infectious Disease • Leukemia • Lymphoma • Neutropenia • Oncology • Septic Shock • Thrombocytopenia • BCL2 • IGH • NOTCH1 • SF3B1 • TP53

Systematic Review of Real-World Data on the Effectiveness and Safety Profiles of First-Line Therapies in Chronic Lymphocytic Leukemia (ISPOR-EU 2025) - "OBJECTIVES: To investigate the real-world effectiveness and safety profiles of targeted therapies—such as venetoclax+obinutuzumab (VEN+OBI), ibrutinib (IBR), zanubrutinib (ZAN), acalabrutinib (ACA), and other first-line treatment options—for chronic lymphocytic leukemia (CLL), and to compare these real-world data (RWD) with outcomes reported in randomized controlled trials (RCTs). A systematic review was performed to identify RWD by searching MEDLINE, EMBASE, and the reference lists of eligible studies (search date: January 2, 2025; CRD42024549185)...In contrast, idelalisib+rituximab (IDE+RTX) was associated with lower 24-month OS (77%) and PFS (72%), and the highest TdAE rate (63%)... Among first-line therapies for CLL, IBR has the most extensive and consistent RWD, with results closely reflecting those from RCTs. ZAN and ACA show promising outcomes, while data for VEN+OBI remain limited. IDE+RTX appears less favorable in terms of real-world effectiveness."

Clinical • Real-world • Real-world evidence • Review • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia

Inhibition of Lysine Acetyltransferases p300/CBP Overcomes BTK Inhibitor Resistance in Mantle Cell Lymphoma Cells (ASH 2023) - "We compared three BTKis, ibrutinib, acalabrutinib and tirabrutinib, using DMSO as a control...This effect was even greater than that of existing drugs, including venetoclax (a BCL-2 inhibitor), and idelalisib (a PI3K inhibitor), which are thought to have synergistic effects... Our CRISPR screen identified lysine acetyltransferases p300/CBP as BTK inhibitor resistance genes in human MCL cells. The combination of a p300/CBP inhibitor and a BTK inhibitor synergistically suppresses both BTK and AKT, leading to NFκB suppression. Taken together, we first identified that the combination of p300/CBP inhibition and BTK inhibition could be a promising strategy for treating patients with MCL."

IO biomarker • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Oncology • NFKBIA • PLCG2

Advances in the Management of Relapsed/Refractory CLL and Richter Transformation (ICML 2025) - P=N/A, P2, P3 | "BRUIN CLL-321 is a phase 3, registrational study that evaluated pirtobrutinib compared to the investigator's choice of idelalisib plus rituximab (IdelaR) or bendamustine plus rituximab (BR) [23]...Nemtabrutinib is now being evaluated in the registrational, phase 3 BELLWAVE-010 trial (NCT05947851) for patients with R/R CLL, comparing nemtabrutinib plus venetoclax to venetoclax plus rituximab...An ongoing, open-label, first-in-human phase 1/2 study is evaluating the BTK degrader BGB-16673 as monotherapy in patients with R/R CLL [27, 28]...NX-2127 is an investigational, first-in-class BTK degrader currently being evaluated in a phase 1 trial for patients with relapsed or refractory B-cell malignancies, CLL [29, 30]...NX-5948 is another investigational and more selective BTK degrader in an ongoing Phase 1a/1b clinical trial...This trial aims to establish lisaftoclax plus acalabrutinib as a potential alternative to venetoclax-based BTKi combination..."

IO biomarker • Acute Myelogenous Leukemia • B Cell Lymphoma • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Leukemia • Non-Hodgkin’s Lymphoma • Oncology • Richter's Syndrome • Small Lymphocytic Lymphoma • BCL2L1 • TP53

Analysis of Ventricular Arrhythmias and Sudden Death with Acalabrutinib from 5 Prospective Clinical Trials (ASH 2023) - " Incidence and relative risk of nonfatal and fatal VAs and SDs were analyzed using pooled data from 5 prospective acalabrutinib clinical trials (nonrandomized trials: CL-001 [acalabrutinib monotherapy], CL-003 [acalabrutinib + obinutuzumab]; randomized trials: CL‑006 [acalabrutinib vs ibrutinib], CL-007 [acalabrutinib ± obinutuzumab vs chlorambucil + obinutuzumab], CL-309 [acalabrutinib vs idelalisib + rituximab OR bendamustine + rituximab]). This pooled analysis of prospective acalabrutinib clinical trials demonstrates that the risk of VA and SD with acalabrutinib is low and similar to that of standard-of-care therapies when adjusted for exposure. The current analysis with more than 1200 patients treated with acalabrutinib points to favorable safety outcomes and no specific trend with SDs and VAs. Additional analyses with larger cohorts from the clinical development program and all postmarketing sources will continue to further characterize the safety profile of..."

Clinical • Atrial Fibrillation • Cardiovascular • Chronic Lymphocytic Leukemia • Hematological Malignancies • Hypertension • Leukemia • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma

The Pharmacological Atlas of Meningiomas (SNO 2025) - "The top five drugs with the lowest IC50 values were romidepsin, dactinomycin, carfilzomib, plicamycin, and omacetaxine, with median values of 10, 31, 145, 303, and 400 nM, respectively. Considering the ratio of peak serum concentration (Cmax) to IC50 as a potential predictor of treatment efficacy (>1), the HDAC inhibitors belinostat (74.5), romidepsin (69.7), along with the proteasome inhibitor carfilzomib (34.6), and the anthracyclines epirubicin (2.6), and doxorubicin (1.8), and the PI3K inhibitor idelalisib (1.6) are the most promising drug candidates for further evaluation. This study offers the first comprehensive insight into the pharmacological landscape of meningiomas, providing a crucial foundation for future clinical trials aimed at developing systemic treatments for aggressive meningiomas."

Brain Cancer • Meningioma • Solid Tumor

Targeted therapies and resistance mechanisms in lymphoma: Current landscape and emerging solutions. (PubMed, Oncoscience) - "We comprehensively evaluate FDA-approved targeted agents, including monoclonal antibodies (rituximab, brentuximab vedotin, obinutuzumab, mogamulizumab), immune checkpoint inhibitors (nivolumab, pembrolizumab), CAR T-cell therapies (axi-cel, tisa-cel, liso-cel, brexu-cel), bispecific T-cell engagers (mosunetuzumab, epcoritamab), and small-molecule inhibitors (ibrutinib, idelalisib, venetoclax). In conclusion, understanding the molecular basis of lymphoma and resistance mechanisms is critical to optimizing targeted therapy. This review synthesizes current evidence to inform clinical decision-making and outlines future directions for durable, personalized lymphoma care."

IO biomarker • Journal • Review • Hematological Disorders • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • BTK • CCR4 • CD20 • TNFRSF8

BRIDGING THERAPY TO CAR-T CELLS IN RELAPSED/ REFRACTORY SECONDARY CENTRAL NERVOUS SYSTEM B NON-HODGKIN LYMPHOMAS (SIE 2025) - "Pts had leukapheresis (LK): Axi-cel (n=9/25,36%), Tisa-cel (n=7/25,28%), Liso-cel 7/25,28%), and Brexu-cel (n=2/25,8%)...CT were: Etoposide-Ifosfamide (HLXVP16)+/-Rituximab(R)(n=10), R-Methotrexate-Cytarabine (R-MTXARAC)(n=2), R-Gemcitabine-Oxaliplatin (n=1), R-HLX-Cisplatin-VP16 (n=1), R-Dexamethasone-ARAC-Oxaliplatin (R-DHAX)(n=1). CT+TT (concomitant and/or sequential) included R-HLX-VP16+Ibrutinib (Ibru)(n=1) or Lenalidomide (Len)(n=1), R-MTX-ARAC/R-HLXVP16+Zanubrutinib (n=1), R-DHAX/Ibru (n=1). TT were: Venetoclax (n=1), Ibru (n=1), Idelalisib (n=1), Len (n=1)...In conclusion, BT in SCNSL is safe and can improve disease control as well as PS leading to a high injection rate in this population characterized by a dismal outcome. Despite a small population, our data suggest encouraging results for combination strategies of BT."

CAR T-Cell Therapy • Anemia • B Cell Lymphoma • CNS Lymphoma • Hematological Disorders • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Secondary Central Nervous System Lymphoma

Dual PI3Kδ/γ inhibition enhances radiotherapy-induced antitumor immunity via macrophage-dependent cGAS-STING-type I interferon signaling. (PubMed, Biochem Biophys Res Commun) - "In the syngeneic CT26 model, dual PI3Kδ/γ inhibition (BR101801 or duvelisib), unlike selective PI3Kδ inhibition (idelalisib), synergized with RT (7.5 Gy) to suppress tumor growth and induce durable immune memory. Furthermore, blockade of the IFN-I receptor abolished CD8+ T cell infiltration and M2-like macrophage suppression, abrogating antitumor efficacy and confirming the requirement for IFN-I signaling. These findings identify macrophage-driven activation of the cGAS-STING-IFN-I axis as a key mechanism by which dual PI3Kδ/γ inhibition potentiates RT, providing a strong scientific rationale for its development as an immunomodulatory radiosensitizer."

Journal • Colorectal Cancer • Oncology • Solid Tumor • CD8 • CGAS • CXCL10 • PIK3CD • PIK3CG • STING

Silico, in vitro, and in vivo studies of a 2-substituted quinazolin-4(3H)-one in T-cell acute lymphoblastic leukemia. (PubMed, Toxicol Appl Pharmacol) - "Comparative analysis with idelalisib revealed similar toxicity profiles to Qona11, distinct from vincristine. In vivo studies in NOD/SCID mice bearing Jurkat xenografts showed that Qona11 (100 mg.kg-1) was well tolerated with no systemic toxicity, although it did not inhibit leukemia cell proliferation in immune-independent models. Overall, Qona11 exhibits promising anticancer activity and low systemic toxicity, warranting further preclinical investigation in solid tumor models and combination therapies."

Journal • Preclinical • Acute Lymphocytic Leukemia • Cardiovascular • Hematological Malignancies • Leukemia • Oncology • Solid Tumor • T Acute Lymphoblastic Leukemia • T-cell Acute Lymphoblastic Lymphoma • CASP3

A Study of DZD8586 Versus Investigator's Choice in r/r CLL/SLL (TAI-SHAN6) (clinicaltrials.gov) - P3 | N=250 | Recruiting | Sponsor: Dizal (Jiangsu) Pharmaceutical Co., Ltd. | Not yet recruiting ➔ Recruiting

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

Establishing a lymphoma patient-derived xenograft (PDX) in vivo platform (DGHO 2025) - "These are mostly derived from heavily pre-treated patients (e.g. failure of high-dose chemotherapy, bortezomib, venetoclax, ibrutinib, pirtobrutinib, idelalisib or CAR T-cell therapy). Our constantly growing well-characterized lymphoma PDX repository provides a promising versatile experimental platform to expand lymphoma in vivo studies."

Preclinical • B Cell Lymphoma • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Gastrointestinal Disorder • Hematological Malignancies • Large B Cell Lymphoma • Leukemia • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • CCND1 • CD34 • PRKDC • SOX11

Mapping the Drug Combination Landscape for AML: An Integrative Ex Vivo Functional and Computational Approach (ASH 2024) - "Clinical outcomes and ex vivo Venetoclax+Azacitidine (VenAza) DSS were derived from 12 patients treated with VenAza (Chow et al...Notably, 68 combinations surpassed VenAza in both efficacy and CI, including approved drug partners like Ven (n=12), Trametinib (n=11) and Idelalisib (n=11)...These clusters showed differential response towards 77 combinations, with biases in primitive clusters for Ven + Aza/Ibrutinib and mature clusters for Ven + Palbociclib/Quizartinib...By integrating multiomics data and rigorously testing over 100 different variables, our findings reinforced cell maturation states as determinants of combination drug responses. A novel finding reveals maturation status is accompanied by activation of inflammatory states in AML, indicating a role of differentiation block in shaping immune response."

Preclinical • Acute Myelogenous Leukemia • Oncology • FLT3 • NPM1

Resistance to FLT3 Inhibitors in FLT3-Mutated AML Is Associated with CD45RA+CD200- leukemic Cells and Can be Overcome By Combination with SMAC Mimetics (ASH 2024) - "Subsequent validation confirmed synergy between the midostaurin and the SMAC-mimetics birinapant and LCL161, while the BH3 mimetic venetoclax and the PI3K inhibitor idelalisib only showed an additive effect. Our data shows specific differences in myeloid maturation and LSC (Leukemic Stem Cell) phenotype between midostaurin responders and non-responders, together with a potential functional shift in cell signaling in immune signaling and anti-apoptotic pathways. Moreover, ex vivo drug testing data demonstrates that while there is less overall sensitivity to drug treatment in non-responders, combination therapies including apoptotic modulators such as the SMAC mimetics could overcome FLT3i resistance and improve FLT3mut patient outcomes."

IO biomarker • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CD200 • CD33 • CD40 • FLT3 • IL12RB1 • ITGAX • PD-L1