Zydelig (idelalisib) / Gilead - LARVOL DELTA

High Karyotypic Complexity and Translocations Are Adverse Prognostic Features in Patients with Chronic Lymphocytic Leukemia without TP53 Aberrations Treated with Venetoclax-Based Time-Limited Combinations (ASH 2022) - "Studies on the prognostic impact of CKT with targeted agents are not only heterogeneous in size and methodologies but also conflicting, with reports on both negative impact (venetoclax [ven] + rituximab [RVe] and ibrutinib monotherapy) and no impact (ven + obinutuzumab [GVe], ven + ibrutinib, idelalisib + rituximab) on progression-free (PFS) and overall survival (OS). In pts lacking TP53 aberrations, hCKT (≥5 CA) but not iCKT (3-4 CA) was associated with shorter PFS following treatment with time-limited ven combinations. While this study confirms the adverse impact of CKT with CIT, it identifies hCKT as an adverse prognostic factor in the context of ven-based combination treatment in CLL. Presence of translocations was associated with inferior PFS in all treatment arms."

Clinical • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • IL2 • TP53

Final Analysis of the Prospective Multicenter CLL2-Give Trial of Obinutuzumab (GA101, G), Ibrutinib (I), and Venetoclax (Ve) in Untreated Patients with CLL with 17p Deletion/TP53 Mutation (ASH 2022) - "Subsequent treatments were administered in 4 pts (1 pt with 3 therapies: venetoclax, idelalisib/rituximab, ibrutinib; obinutuzumab (n=1); acalabrutinib/venetoclax/obinutuzumab (n=2)). Most common cardiac disorder of any grade was atrial fibrillation in 14.6% of pts. Conclusion The CLL2-GIVe regimen is a potent and promising fixed-duration, first-line treatment for pts with high-risk CLL with a manageable safety profile worthy of further exploration in phase 3 studies."

Clinical • Atrial Fibrillation • Cardiovascular • Chronic Lymphocytic Leukemia • Congestive Heart Failure • Gastroenterology • Gastrointestinal Disorder • Heart Failure • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Neutropenia • Novel Coronavirus Disease • Oncology • Ovarian Cancer • Respiratory Diseases • Richter's Syndrome • Solid Tumor • Thrombocytopenia • IGH • TP53

EFFICACY OF PEMBROLIZUMAB MONOTHERAPY AND IN COMBINATION WITH BCR INHIBITORS FOR RICHTER TRANSFORMATION OF CHRONIC LYMPHOCYTIC LEUKEMIA (EHA 2024) - "Sixteen patients went on to receive a BCR kinase inhibitor (ibrutinib [n=15], idelalisib [n=1]) in combinationwith pembrolizumab, after SD or PD on pembrolizumab monotherapy. This expanded analysis confirmed that pembrolizumab has modest single agent activity in RT. Combinationtherapy with pembrolizumab and a BCR kinase inhibitor is associated with increased efficacy (ORR >60%),similar to other reports. These results support further investigation of immune checkpoint inhibitor-basedcombination therapy in RT."

Clinical • Combination therapy • IO biomarker • Monotherapy • Anemia • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Leukopenia • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Pneumonia • Pulmonary Disease • Richter's Syndrome • Thrombocytopenia • TP53

Zanubrutinib, a New Bullet Against Chronic Lymphocytic Leukemia Even When Localized in Central Nervous System. (PubMed, Case Rep Hematol) - "We report the case of a 45-year-old woman with refractory CLL who developed CNS and extralymphatic lesions after three prior lines of therapy, including rituximab-bendamustine, rituximab-idelalisib, and rituximab-venetoclax...Zanubrutinib's enhanced blood-brain barrier (BBB) penetration and favorable safety profile make it a promising option for CNS-CLL and also for other extralymphatic lesions. This case underscores the potential of zanubrutinib in addressing challenging CLL presentations."

Journal • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology

BRUIN CLL-321: Randomized Phase III Trial of Pirtobrutinib Versus Idelalisib Plus Rituximab (IdelaR) or Bendamustine Plus Rituximab (BR) in BTK Inhibitor Pretreated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (ASH 2024) - P3 | "Methods : Eligible CLL/SLL pts previously treated with cBTKi were randomized 1 : 1 to receive pirtobrutinib monotherapy (200mg QD) or IC of IdelaR or BR and stratified by prior use of venetoclax and del(17p) status. Summary/Conclusion : BRUIN CLL-321 is the first randomized study conducted exclusively in cBTKi pretreated CLL/SLL pts. In this heavily pretreated patient population with poor prognosis, pirtobrutinib treatment led to a significant improvement in PFS compared to IC, along with a more favorable safety profile."

Clinical • P3 data • Anemia • Atrial Fibrillation • Cardiovascular • Chronic Lymphocytic Leukemia • Fatigue • Hematological Disorders • Hematological Malignancies • Hypertension • Infectious Disease • Leukemia • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Pneumonia • Respiratory Diseases • Small Lymphocytic Lymphoma • IGH • TP53

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

Study Design and Baseline Characteristics of AURORA, a Randomized Placebo-Controlled Double-Blind Study of CAL101 in IPF (ERS 2026) - "This provides context for interpretation of the Week 28 efficacy analysis of CAL101. Parameter AURORA population (N=84)* Male sex 72 (86) Age, yrs 71.1 (6.7) IPF disease duration, yrs 3.4 (2.6) Background antifibrotic therapy Nintedanib Pirfenidone None 41 (49) 33 (39) 10 (12) FVC Absolute, mL % predicted 2807 (829) 76.5 (17.2) Extent of lung fibrosis, % (n=75) 15.0 (8.4) DLCO, % predicted 52 (15.9) Supplemental oxygen use 8 (10) Data presented as mean (SD) or n (%) *Randomized by 31 Jan, 2026"

Clinical • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Inflammation • S100A4

Phase III Trial of Pirtobrutinib Versus Idelalisib/Rituximab or Bendamustine/Rituximab in Covalent Bruton Tyrosine Kinase Inhibitor-Pretreated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (BRUIN CLL-321). (PubMed, J Clin Oncol) - "Pirtobrutinib improved PFS and TTNT, and demonstrated favorable tolerability, versus IdelaR/BR in exclusively cBTKi pretreated patients with CLL/SLL."

Journal • P3 data • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma

Acalabrutinib versus rituximab plus idelalisib or bendamustine in relapsed/refractory chronic lymphocytic leukemia: ASCEND results at 4 years of follow-up. (ASCO 2022) - P3 | "At ~4 years of follow-up, acala maintained efficacy compared with standard-of-care regimens and a consistent tolerability profile in R/R CLL."

Atrial Fibrillation • Cardiovascular • Chronic Lymphocytic Leukemia • Hematological Disorders • Hematological Malignancies • Hypertension • Infectious Disease • Leukemia • Oncology • IGH

REAL-WORLD OUTCOME OF PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA (CLL) TREATED WITH BTK INHIBITORS (BTKI): A SUBGROUP ANALYSIS OF OVER 1100 PATIENTS ENROLLED INTO THE GIMEMA CLL2121 STUDY (EHA 2024) - P=N/A | "852 pts were treated with ibrutinib-based therapies (534 1L, 318 2+L), 278 with acalabrutinib (2111L, 67 2+L), 23 with zanubrutinib (14 1L, 9 2+L), and 6 with pirtobrutinib (1 1L, 5 2+L)...Next line treatment afterthe BTKi was venetoclax-based combinations (62%), covalent BTKi (11%), idelalisib+/-rituximab (9%),chemoimmunotherapy (8%), anti-CD20 monoclonal antibodies (2%), pirtobrutinib (1%), and other (8%)... This real world study conducted on a large cohort of pts with CLL/SLL in Italy shows a high proportion of ptsdiscontinuing BTKi due to toxicity or progression, with a shorter TTNT in TN vs R/R pts, suggesting a lowerthreshold to switch treatment in clinical practice. BTKi discontinuation is a turning point in the disease history,that portends a short overall survival, with limited salvage options, being mainly venetoclax as also in ourseries. Additional analysis on an extended cohort will be presented at the meeting."

Clinical • IO biomarker • Real-world • Real-world evidence • Chronic Lymphocytic Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma • IGH

Reveal the diagnostic value of a neutrophil inflammation- and cell death-associated gene signature in rheumatoid arthritis. (PubMed, Medicine (Baltimore)) - "The GEO dataset GSE110169 was used as the training dataset to identify differentially expressed genes between RA patients and healthy controls...However, because direct NET markers were not experimentally evaluated, the selected genes should not be interpreted as NETs-specific biomarkers. Further experimental validation is required."

Gene Signature • Journal • Immunology • Inflammation • Inflammatory Arthritis • Ocular Inflammation • Primary Immunodeficiency • Rheumatoid Arthritis • Rheumatology • CLEC7A • ENO1 • OPA1 • RIPK1 • S100A8

PATIENT REPORTED OUTCOMES FROM BRUIN CLL-321: PHASE 3 TRIAL COMPARING PIRTOBRUTINIB TO IDELALISIB/RITUXIMAB OR BENDAMUSTINE/RITUXIMAB IN COVALENT BTKi PRETREATED CLL/SLL (ICML 2025) - "These analyses suggest a meaningful and clinically relevant improvement in CLL/SLL-related symptoms, physical functioning, and fatigue at most assessments between baseline and Week 25 in the pirtobrutinib group compared to IdelaR/BR. Most PRO assessments met clinically meaningful thresholds, and for those that did not there remained a consistent directional difference in favor of pirtobrutinib, suggesting a consistent benefit in terms of PF, CLL/SLL-related symptoms, and fatigue versus IdealR/BR. Keyword: chronic lymphocytic leukemia (CLL)"

Clinical • P3 data • Patient reported outcomes • Chronic Lymphocytic Leukemia • Lymphoma • Small Lymphocytic Lymphoma

Efficacy, Safety, and Resistance in Pirtobrutinib-Treated Chronic Lymphocytic Lymphoma/Small Lymphocytic Lymphoma After Covalent BTK Inhibitor Failure: A Systematic Review of the BRUIN Trial Program (SOHO 2026) - "BRUIN CLL-321 (n = 238, post-cBTKi) confirmed superiority over standard salvage therapy: median PFS 14.0 vs 8.7 months (HR, 0.54; 95% CI, 0.39–0.75), with fewer grade ≥3 adverse events and lower discontinuation rates vs idelalisib +rituximab or bendamustine+rituximab. Pirtobrutinib demonstrates consistent, durable efficacy across CLL treatment lines: ORR exceeding 73% post-cBTKi and an 80% reduction in progression risk in the frontline setting. Its favorable tolerability profile, particularly the low rates of atrial fibrillation and treatment discontinuation, addresses key limitations of prior BTK inhibitors. These findings establish pirtobrutinib as a transformative agent in CLL and support its integration into earlier treatment lines and combination strategies."

Clinical • IO biomarker • Review • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma

A first-in-human study of CAL101, a monoclonal antibody targeting S100A4. (PubMed, Br J Clin Pharmacol) - "CAL101 demonstrated an acceptable safety profile, predictable PK and PD effects consistent with extracellular S100A4 neutralization. These findings support further clinical development of CAL101 in fibro-inflammatory diseases."

Clinical • Journal • Dermatology • Immunology • Inflammation • Psoriasis • S100A4

Pirtobrutinib vs Idelalisib Plus Rituximab in Chronic Lymphocytic Leukemia: A Propensity-Matched Real-World Analysis (SOHO 2026) - "In this propensity-matched real-world analysis, pirtobrutinib was associated with significantly lower relapse and mortality compared with idelalisib plus rituximab in CLL. Given the substantial mortality difference, residual confounding by indication, particularly differential patient frailty and prior therapy burden, cannot be excluded and warrants cautious interpretation. The unrestricted diagnosis date window may also introduce survivorship bias, as idelalisib plus rituximab patients with older index dates could reflect a more treatment-refractory historical population."

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

IGF2BP1 Inhibition Impairs PI3K Signaling and Drives Metabolic Reprogramming in B-Cell Acute Lymphoblastic Leukemia (SOHO 2026) - "Our findings suggest that IGF2BP1 plays an important role in B-ALL by synergistically interacting with the PI3K pathway and influencing metabolism. Therefore, targeting IGF2BP1 and its associated pathways could be a potential therapeutic approach. BTYNB: 2-[[(5-bromo-2-thienyl)methylene]amino]-benzamide, CAL-101: idelalisib, CD19: cluster of differentiation 19, CRISPR: clustered regularly interspaced short palindromic repeats, ETV6::RUNX1: ETS variant transcription factor 6::RUNX1 partner transcriptional corepressor 1, G1: growth 1, LC-MS: liquid chromatography–mass spectrometry, MRD: measurable residual disease, PI3K: phosphoinositide 3-kinase, RT-qPCR: reverse transcription-quantitative polymerase chain reaction, TCA: tricarboxylic acid."

Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology • ETV6 • IGF2 • IGF2BP1 • RUNX1 • RUNX1T1 • TFAM

A comprehensive analysis of pirtobrutinib in Chinese patients with chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL): Results from the phase 3 study BRUIN CLL-321. (PubMed, Br J Haematol) - "In this heavily pretreated population, pirtobrutinib significantly improved progression-free survival (PFS) compared to investigator's choice (IC) of idelalisib/rituximab (IdelaR) or bendamustine/rituximab (BendaR). Pirtobrutinib showed a favourable safety profile, with fewer grade ≥3 treatment-emergent adverse events (36.8% vs. 93.3%) and serious adverse events (15.8% vs. 46.7%). These findings support pirtobrutinib as a clinically active and tolerable option for cBTKi-pretreated Chinese CLL/SLL population."

Journal • P3 data • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma

Predictive and concurrent validity of caregiver reported early childhood development assessments: A prospective cohort study of Tanzanian children. (PubMed, PLOS Glob Public Health) - "This study examined the predictive validity of the Caregiver-Reported Early Development Instrument (CREDI) at 12 months of age with the directly assessed International Early Learning and Development Assessment (IDELA) and the caregiver-reported Early Childhood Development Index 2030 (ECDI 2030) administered at 3.5-6 years of age...Our results demonstrate limited predictive power from a caregiver-reported assessment administered in infancy, highlighting how variable ECD is for young children. At preschool age, a directly assessed measure of ECD had better reliability than a shorter caregiver-reported measure, but scores on both measures correlated strongly, suggesting that caregiver-reported measures are capturing similar constructs to directly assessed measures of ECD when implemented at the same point in time."

Journal

Utility of mouse precision cut lung slices as an in vitro model for interrogating the lung immune response against bacterial pathogens in the context of immunomodulatory therapeutics. (PubMed, Respir Res) - "Naïve mouse PCLS were pre-treated with immunomodulatory drugs previously reported to exacerbate clinical infection risk (Idelalisib, Anakinra and Tofacitinib), followed by incubation with the lung pathogen Streptococcus pneumoniae. Notably, these pathways were modulated in the presence of Idelalisib and translation of the involvement of these pathways in the response to S. pneumoniae was confirmed in NHBE. In conclusion, the PCLS model offers potential to inform early risk assessment whilst aiding mechanistic understanding of the immunomodulatory impact of drug candidates on the lung."

Journal • Preclinical • Infectious Disease • Pneumococcal Infections • Pneumonia • Respiratory Diseases

Sex-Specific Safety Profiles of PI3K Inhibitors: A Real-World Pharmacovigilance Study Based on FAERS Database. (PubMed, Clin Ther) - "This research identifies sex-specific AE patterns for PI3K inhibitors. Subsequent to FDR correction, significant PT level sex differences were detected for alpelisib, yet not for idelalisib. Moreover, no differences at the standard of care SOC level persisted for either drug. The findings regarding copanlisib and duvelisib remain indeterminate. These results provide clinically relevant signals for sex-tailored AE surveillance and necessitate prospective validation."

Adverse events • Journal • Real-world evidence • Diabetes

Exposure-informed lung transcriptomic analysis links predicted NNK targets to cell type-specific remodeling programs in idiopathic pulmonary fibrosis. (PubMed, Funct Integr Genomics) - "The fixed epithelial ExposureA-core Top30 signature remained detectable in independent bulk lung transcriptomic cohorts without gene re-selection, coefficient fitting, or score optimization, with exploratory ROC analyses showing apparent IPF-control separation in GSE110147 and GSE92592...Overall, this study defines a focused exposure-informed IPF-associated transcriptional framework and prioritizes epithelial remodeling-related candidate features for future experimental validation. These findings support hypothesis-generating computational prioritization rather than direct evidence that NNK drives IPF pathogenesis."

Journal • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases • MMP7 • TGM2

Synergistic Profiling of Programmed Cell Death and Immune Responses Identifies a Novel Prognostic Index for Cervical Cancer. (PubMed, ACS Omega) - "Profiling of drug susceptibility revealed that the high-risk cohort of patients showed resistance to rapamycin and idelalisib but were sensitive to thapsigargin and linsitinib. Overall, the ICDI shows strong potential as a prognostic marker for forecasting clinical outcomes and could facilitate personalized treatment strategies for CC patients."

Journal • Cervical Cancer • Oncology • Solid Tumor • FADD • MUC4

School readiness and its determinants among children 4 to 6 years in Zanzibar: a baseline population-based cross-sectional survey. (PubMed, Front Public Health) - "School readiness was measured using the International Development and Early Learning Assessment (IDELA) with household vulnerability being measured by FHI360 Household Vulnerability Assessment Tool (HVAT)...A substantial proportion of preschool children in Zanzibar enter formal schooling without adequate readiness. Strengthening ECD strategies is required, with priority given to rural communities and vulnerable households to advance progress toward universal access to quality ECD and pre-primary education."

Journal

Cyclodextrin-Mediated Enantiomeric Separation of Idelalisib: A Validated Capillary Electrophoresis and NMR Study. (PubMed, Int J Mol Sci) - "These interactions may account for the superior enantioseparation observed with HP-β-CD of intermediate DS. Our validated CE method addresses the distomer determination while NMR insights provide mechanistic understanding of the chiral recognition."

Journal • Oncology

Gastrointestinal toxicity in the treatment of hematological tumors. Influence on nutritional status. (PubMed, Endocrinol Diabetes Nutr (Engl Ed)) - "Understanding the frequency and severity of gastrointestinal side effects of drugs used to treat hematological malignancies can facilitate early diagnosis and medical-nutritional management, which can be key to reducing malnutrition and improving clinical outcomes in hematological tumors."

Journal • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Chronic Lymphocytic Leukemia • Chronic Myeloid Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Mucositis • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • Sarcopenia