Leukeran (chlorambucil) / Aspen Pharma, GSK - LARVOL DELTA

Fixed-duration ibrutinib-venetoclax versus chlorambucil-obinutuzumab in previously untreated chronic lymphocytic leukaemia (GLOW): 4-year follow-up from a multicentre, open-label, randomised, phase 3 trial. (PubMed, Lancet Oncol) - P3 | "After 4 years of follow-up, ibrutinib-venetoclax continues to significantly prolong progression-free survival (vs chemoimmunotherapy) in patients with previously untreated chronic lymphocytic leukaemia, supporting its use as a first-line option."

IO biomarker • Journal • P3 data • Cardiovascular • Chronic Lymphocytic Leukemia • Congestive Heart Failure • Heart Failure • Hematological Malignancies • Infectious Disease • Leukemia • Myelodysplastic Syndrome • Oncology • Pneumonia • Respiratory Diseases • IGH

Real-World Clinical Outcomes of Targeted Therapy in a Pakistani Cohort of Chronic Lymphocytic Leukemia (SOHO 2026) - "Patients were managed with ibrutinib, acalabrutinib, chlorambucil, or observation ("watch and wait"). BTK inhibitor-based therapy demonstrated favorable efficacy and tolerability in this real-world Pakistani CLL cohort, supporting the expanding role of targeted therapies in improving outcomes, even in advanced disease."

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

RITUXIMAB AND IBRUTINIB COMBINATION IS SAFE AND EFFECTIVE IN UNTREATED SPLENIC AND NODAL MARGINAL ZONE LYMPHOMAS: PLANNED SUBSET ANALYSIS OF THE IELSG47/MALIBU PHASE II STUDY (ICML 2023) - "The research was funded by: The research was supported partially by Janssen (financial and drug supply) and Roche (drug supply) Introduction: Although in a phase III trial of extranodal MZL (EMZL) patients (pts) the combination of rituximab and chlorambucil had superior progression-free and event-free survival (PFS, EFS) compared to either drug given alone (Zucca et al. The combination of rituximab and ibrutinib shows promising activity, especially in SMZL, with an acceptable toxicity profile."

P2 data • Hematological Malignancies • Lymphoma • Marginal Zone Lymphoma • Oncology

Long-term outcomes of chemoimmunotherapy with obinutuzumab/chlorambucil in chronic lymphocytic leukemia. (PubMed, Blood Adv) - No abstract available

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

Transcriptomic profiles and 5-year results from the randomized CLL14 study of venetoclax plus obinutuzumab versus chlorambucil plus obinutuzumab in chronic lymphocytic leukemia. (PubMed, Nat Commun) - P3 | "These data indicate sustained long-term efficacy of fixed-duration Ven-Obi in patients with previously untreated CLL. The distinct transcriptomic profile of MRD+ status suggests possible biological vulnerabilities."

Clinical • IO biomarker • Journal • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • ABCB1 • BCL2L11 • CD19

Acalabrutinib ± obinutuzumab versus obinutuzumab + chlorambucil in treatment-naïve chronic lymphocytic leukemia: Five-year follow-up of ELEVATE-TN. (ASCO 2022) - P3 | "After a 5-y follow-up, efficacy and safety of A+O and A monotherapy were maintained, with significantly longer OS in the A+O arm compared with O+Clb."

Chronic Lymphocytic Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology

VENETOCLAX-OBINUTUZUMAB FOR PREVIOUSLY UNTREATED CHRONIC LYMPHOCYTIC LEUKEMIA: 6-YEAR RESULTS OF THE RANDOMIZED CLL14 STUDY (ICML 2023) - " Pts with previously untreated CLL and coexisting conditions were randomized 1:1 to Ven-Obi or chlorambucil-obinutuzumab (Clb-Obi). These data confirm a long-term PFS benefit of fixed-duration Ven-Obi treatment compared to Clb-Obi, including pts with high-risk CLL. Five years after completing Ven-Obi, over half of pts remained in remission, and over 60% had not required second-line treatment. The 1-year Ven-Obi regimen is an effective fixed-duration option for pts with CLL and coexisting conditions."

Clinical • Hematological Malignancies • Lymphoma • Oncology • IGH • TP53

First-Line Fixed-Duration Ibrutinib Plus Venetoclax (Ibr+Ven) Versus Chlorambucil Plus Obinutuzumab (Clb+O): 55-Month Follow-up from the Glow Study (ASH 2023) - P3 | "With prolonged follow-up of 55 months in the GLOW study, all-oral, once-daily, fixed-duration Ibr+Ven continues to show superior PFS versus Clb+O. Among patients treated with Ibr+Ven, benefit in PFS was particularly observed in patients with uIGHV who achieved uMRD at EOT+3 and in patients with mIGHV regardless of MRD status at EOT+3. Moreover, Ibr+Ven fixed-duration combination treatment continues to demonstrate an OS advantage versus chemoimmunotherapy in patients with previously untreated CLL."

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

Ibrutinib Plus Venetoclax with MRD-Directed Duration of Treatment Is Superior to FCR and Is a New Standard of Care for Previously Untreated CLL: Report of the Phase III UK NCRI FLAIR Study (ASH 2023) - "A Phase III trial comparing I+V (15 months [mo]) with chlorambucil-obinutuzumab led to the approval of I+V. Ibrutinib plus venetoclax significantly improved progression-free and overall survival compared to FCR in untreated CLL. Using MRD to direct the duration of I+V maximizes outcome with 97.2% progression free survival at 3 years The efficacy seen in FLAIR is superior to previous Phase III CLL trials indicating that I+V with duration guided by MRD is a new gold standard for CLL treatment."

IO biomarker • P3 data • Acute Myelogenous Leukemia • Chronic Lymphocytic Leukemia • Infectious Disease • Oncology • IGH

Risk of Therapy-Related Myeloid Neoplasms in Patients With Chronic Lymphocytic Leukemia Treated With BTK Inhibitors: A Retrospective Multicenter Analysis Using the TriNetX Database (SOHO 2026) - "Adult patients with CLL treated with ibrutinib, acalabrutinib, or zanubrutinib were included. Patients with prior chemoimmunotherapy exposure, including fludarabine/cyclophosphamide, FCR, bendamustine/rituximab, and obinutuzumab/chlorambucil, were excluded to better isolate the long-term effects of BTKi therapy... In this large real-world TriNetX analysis of patients with CLL treated with BTK inhibitors and without prior chemoimmunotherapy exposure, therapy-related myeloid neoplasms were uncommon but increased over longer follow-up. MDS was the most frequent secondary myeloid neoplasm, followed by AML. The underlying immune dysregulation inherent to CLL, including impaired immune surveillance and defective T-cell function, may also contribute to the development of secondary malignancies in this population."

Retrospective data • Acute Myelogenous Leukemia • Chronic Lymphocytic Leukemia • Chronic Myelomonocytic Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Myeloproliferative Neoplasm • Oncology

Final analysis of the RESONATE-2 study: up to 10 years of follow-up of first-line ibrutinib treatment for CLL/SLL. (PubMed, Blood) - P3 | "With up to 10 years of follow-up, we report results from the final analysis of RESONATE-2 (NCT01722487/NCT01724346), a phase 3 study of first-line ibrutinib versus chlorambucil for the treatment of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). With the longest follow-up to date from a phase 3 study of any targeted CLL/SLL therapy, this landmark RESONATE-2 study defines median PFS and demonstrates continued OS benefit of first-line ibrutinib treatment for patients with CLL/SLL, including those with high-risk genomic features. Sustained efficacy and tolerability of ibrutinib reemphasize the favorable benefit-risk profile."

Journal • Cardiovascular • Chronic Lymphocytic Leukemia • Cough • Fatigue • Hematological Malignancies • Hypertension • Leukemia • Lymphoma • Musculoskeletal Pain • Non-Hodgkin’s Lymphoma • Oncology • Respiratory Diseases • Small Lymphocytic Lymphoma • IGH • TP53

FINAL ANALYSIS OF THE RESONATE-2 STUDY: UP TO 10 YEARS OF FOLLOW-UP OF FIRST-LINE IBRUTINIB TREATMENT IN PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA/SMALL LYMPHOCYTIC LYMPHOMA (EHA 2024) - P3 | " In this phase 3 study of older adults (≥65 years) with previously untreated CLL/SLL without del(17p), patients(pts) were randomly assigned 1:1 to receive either single-agent Ibr (n=136) or chlorambucil (Clb) (n=133). With the longest follow-up to date from a phase 3 study of any targeted therapy for CLL/SLL, this final analysisof the landmark RESONATE-2 study defines median PFS and demonstrates continued OS benefit of single-agent Ibr treatment for pts with previously untreated disease, including those with high-risk genomic features. Median PFS was significantly longer with Ibr versus Clb, and responses to Ibr were sustained over time. Atstudy completion, 27% of pts remained on Ibr, AE rates were stable, and no new safety signals emerged sincethe prior report."

Clinical • IO biomarker • Atrial Fibrillation • Cardiovascular • Chronic Lymphocytic Leukemia • Hematological Malignancies • Hypertension • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma • IGH • TP53

Venetoclax, Obinutuzumab and Atezolizumab (PD-L1 Checkpoint Inhibitor) for Treatment for Patients with Richter Transformation (ASH 2021) - P2 | "Previous therapy for CLL included ibrutinib, n=4; chlorambucil + OBIN and then acalabrutinib, n=1; BR, n=1; one pt had no prior therapy for CLL)...R/R RT (n=1) : One pt (58-year-old male) with previously untreated CLL (unmutated IGHV, del(17p), TP53 mutation, NOTCH1 mutation) developed RT and received R-CHOP for 3 cycles with no response... Treatment with combined VEN, OBIN and atezolizumab leads to high rates of remission in pts with previously untreated RT; all 7 pts achieved a remission and 3 pts proceeded to allo-SCT. With the limitation of small numbers, these results are encouraging in relation to combined ibrutinib plus nivolumab in previously untreated RT (7/14, 50% response rate; Jain, ASH 2018). Enrollment in the trial continues and updated data will be presented at the ASH meeting."

Checkpoint inhibition • Clinical • IO biomarker • Bone Marrow Transplantation • Diabetes • Diffuse Large B Cell Lymphoma • Lung Cancer • Melanoma • Metabolic Disorders • Oncology • Pancreatitis • Richter's Syndrome • Solid Tumor • Transplantation • IGH • NOTCH1 • TP53

VENETOCLAX-OBINUTUZUMAB FOR PREVIOUSLY UNTREATED CHRONIC LYMPHOCYTIC LEUKEMIA: 5-YEAR RESULTS OF THE RANDOMIZED CLL14 STUDY (EHA 2022) - "Background One-year fixed-duration venetoclax-obinutuzumab (Ven-Obi) has demonstrated significant improvement of progression-free survival (PFS) as compared to chlorambucil-obinutuzumab (Clb-Obi) in patients with previously untreated chronic lymphocytic leukemia (CLL) and coexisting conditions in the CLL14 trial. The majority of patients treated with Ven-Obi still have not required a second line of CLL therapy. Hence, the 1-year Ven-Obi regimen continues to be an effective fixed-duration option for patients with CLL and coexisting conditions, also in the context of high-risk disease."

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

Venetoclax and Obinutuzumab in Patients with CLL and Coexisting Conditions. (PubMed, N Engl J Med) - P3; "Among patients with untreated CLL and coexisting conditions, venetoclax-obinutuzumab was associated with longer progression-free survival than chlorambucil-obinutuzumab. (Funded by F. Hoffmann-La Roche and AbbVie; ClinicalTrials.gov number, NCT02242942.)."

Clinical • IO biomarker • Journal • Chronic Lymphocytic Leukemia • Hematological Disorders • Hematological Malignancies • Immunology • Leukemia • Neutropenia • Oncology

Characteristics and Clinical Outcomes of Patients with Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma Receiving Ibrutinib for ≥5 Years in the RESONATE-2 Study. (PubMed, Cancers (Basel)) - "Primary results from the phase 3 RESONATE-2 study demonstrated superior efficacy and tolerability with ibrutinib versus chlorambucil in patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). More than half (58%) of ibrutinib-randomized patients benefitted from ibrutinib treatment for ≥5 years regardless of baseline characteristics. Dose modification resolved AEs for most patients, thereby facilitating continued treatment."

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

Residual Disease Kinetics Among Patients with High-Risk Factors Treated with First-Line Fixed-Duration Ibrutinib Plus Venetoclax (Ibr+Ven) Versus Chlorambucil Plus Obinutuzumab (Clb+O): The Glow Study (ASH 2022) - P3 | "All-oral, once-daily, fixed-duration Ibr+Ven achieved uMRD responses that were better sustained than Clb+O during the first 18 months post-treatment. Notably, with Ibr+Ven, uMRD rates were higher and achieved earlier in pts with uIGHV CLL versus mIGHV CLL, while uMRD was similarly sustained post-treatment irrespective of IGHV status. Clinical progressions in the first 18 months post-treatment with Ibr+Ven were uncommon even among pts with detectable MRD ≥ 10-4."

Clinical • IO biomarker • Residual disease • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • IGH • TP53

VENETOCLAX-OBINUTUZUMAB FOR PREVIOUSLY UNTREATED CHRONIC LYMPHOCYTIC LEUKEMIA: 6-YEAR RESULTS OF THE RANDOMIZED CLL14 STUDY (EHA 2023) - " Patients with previously untreated CLL and coexisting conditions wererandomized 1:1 to 12 cycles of venetoclax with 6 cycles of obinutuzumab, or 12 cycles of chlorambucil with 6 cycles of obinutuzumab (Clb-Obi).The primary endpoint was investigator-assessed progression-freesurvival (PFS). These data confirm a long-term PFS benefit of fixed-duration Ven-Obi treatment compared to Clb-Obi, including patients with high-risk CLL.Fiveyears after completing Ven-Obi, over half of patients remained in remission,and over 60% had not required second-linetreatment.The 1-year Ven-Obi regimen is an effectivefixed-duration option for patients with CLL and coexisting conditions. Keywords: Obinutuzumab, Venetoclax, B-CLL, Chronic lymphocytic leukemia"

Clinical • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • Richter's Syndrome • IGH • TP53

Refined Continuous Risk Index for Accurately Predicting Outcomes of Patients With Chronic Lymphocytic Leukemia After Limited-Duration Therapy. (PubMed, J Clin Oncol) - "These results validate CIRI2-CLL in the context of limited-duration CLL therapy. Our approach suggests the models' adaptability to emerging additional longitudinal MRD and/or outcome data. By introducing CIRI2-CLL, we offer a dynamic tool for investigators to reliably identify patients with increased risk of disease relapse after limited-duration therapy with venetoclax and obinutuzumab, freely accessible at CIRI2 (Stanford University), with important implications for informed decision making and for future risk-adapted CLL trial design."

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

Pirtobrutinib Monotherapy for First-Line Chronic Lymphocytic Leukemia: A Non-Anchored Indirect Comparison Using Reconstructed Patient-Level Data. (PubMed, Hematol Rep) - "Compared with pirtobrutinib monotherapy, HRs for PFS were 0.5544 (95%CI, 0.2696-1.1397) versus venetoclax plus obinutuzumab, 0.4583 (95%CI, 0.2066-1.0200) versus venetoclax plus ibrutinib, and 1.4453 (95%CI, 0.6684-3.1240) versus acalabrutinib plus obinutuzumab... This exploratory non-anchored analysis suggests that pirtobrutinib monotherapy may provide PFS outcomes broadly comparable to current first-line combination regimens for CLL. Given the methodological limitations inherent to indirect comparisons, prospective head-to-head studies are needed to clarify the optimal positioning of pirtobrutinib in treatment-naïve CLL."

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

Venetoclax-Obinutuzumab for previously untreated chronic lymphocytic leukemia: 6-year results of the phase 3 CLL14 study. (PubMed, Blood) - P3 | "In the CLL14 study, patients with previously untreated CLL and coexisting conditions were randomized to 12 cycles of Ven-Obi (n=216) or chlorambucil-obinutuzumab (Clb-Obi, n=216). The sustained long-term survival, uMRD and QoL benefits support the use of one-year fixed-duration Ven-Obi in CLL. NCT02242942, EudraCT 2014-001810-24."

Journal • P3 data • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • IGH

Impact of Minimal Residual Disease on Progression-Free Survival Outcomes After Fixed-Duration Ibrutinib-Venetoclax Versus Chlorambucil-Obinutuzumab in the GLOW Study. (PubMed, J Clin Oncol) - "Molecular and clinical relapses were less frequent during the first year post-treatment with ibrutinib + venetoclax versus chlorambucil + obinutuzumab regardless of MRD status at EOT+3 and IGHV status. Even for patients not achieving uMRD (<10), PFS rates remained high with ibrutinib + venetoclax; this is a novel finding and requires additional follow-up to confirm its persistence over time."

Journal • Minimal residual disease • Residual disease • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • IGH

First-line treatment of chronic lymphocytic leukemia with ibrutinib plus obinutuzumab versus chlorambucil plus obinutuzumab: final analysis of the randomized, phase 3 iLLUMINATE trial. (PubMed, Haematologica) - "iLLUMINATE is a randomized, open-label phase 3 study of ibrutinib plus obinutuzumab (n=113) versus chlorambucil plus obinutuzumab (n=116) as first-line therapy for patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma. Eligible patients were aged ≥65 years, or."

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

Treatment Landscape of Relapsed/Refractory CLL in Low-Resource Countries (SOHO 2026) - "First-line therapies included Bruton tyrosine kinase (BTK) inhibitors (ibrutinib/acalabrutinib) in 11 patients (55%), venetoclax-based regimens in 5 patients (25%), and chemoimmunotherapy in 4 patients (20%). In the relapsed setting, second-line treatments included venetoclax-based regimens, BTK inhibitors, bendamustine-rituximab, and chlorambucil-based therapy, according to availability and affordability... Despite financial and diagnostic limitations in low-income countries, patients with R/R CLL can achieve favorable outcomes with targeted therapies, such as BTK inhibitors and venetoclax-based regimens. Improving affordability and access to molecular diagnostics and novel agents is essential to optimize care in resource-limited settings."

IO biomarker • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology

Comparative Efficacy and Safety of Pirtobrutinib vs Covalent BTK Inhibitors in Treatment-Naïve Chronic Lymphocytic Leukemia: A Systematic Review and Bayesian Network Meta-Analysis (SOHO 2026) - "In the NMA (random-effects model), SUCRA rankings were: pirtobrutinib, 75.4%; acalabrutinib-obinutuzumab, 73.7%; zanubrutinib, 60.0%; acalabrutinib, 52.2%; and ibrutinib, 51.3%, with all BTKis ranking substantially above chemotherapy. This independent NMA, the first to connect pirtobrutinib with all approved covalent BTKis in a unified network, shows directionally favorable but nonsignificant PFS comparisons against covalent BTKis under the random-effects model. These findings are limited by indirect estimation and short pirtobrutinib follow-up. A favorable cardiovascular safety profile was observed in direct comparison."

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