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

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

ELEVATE-TN: Acalabrutinib, Obinutuzumab and Chlorambucil in Treatment naïve CLL (clinicaltrials.gov) - P3 | N=535 | Active, not recruiting | Sponsor: Acerta Pharma BV | Trial primary completion date: Dec 2019 ➔ Feb 2019

Monotherapy • Trial primary completion date • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Oncology • CD20 • CD5 • FCER2

Cost Effectiveness of First-Line Therapies for Treatment-Naïve Chronic Lymphocytic Leukaemia in South Africa. (PubMed, Clin Drug Investig) - "In the South African public healthcare setting, CIT regimens (FCR and BR) represent cost-effective first-line treatment strategies for symptomatic, treatment-naïve CLL. Bendamustine-plus-rituximab emerged as the most decision-robust option under uncertainty, while FCR yielded the lowest point-estimate ICER. Among CIT regimens, FCR may be preferred in fit patients, while BR represents a more decision-robust option in older or unfit populations. Targeted therapies such as ibrutinib and VenO, despite superior clinical efficacy, are not cost effective at current prices. Substantial price reductions, generic entry, or targeted use in high-risk subgroups may improve their value and enable equitable access within South Africa's resource-constrained health system."

HEOR • Journal • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • 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

ELEVATE-TN: Acalabrutinib, Obinutuzumab and Chlorambucil in Treatment naïve CLL (clinicaltrials.gov) - P3 | N=510 | Recruiting | Sponsor: Acerta Pharma BV | Not yet recruiting ➔ Recruiting

Enrollment open • Monotherapy • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Oncology • CD20 • CD5 • FCER2

ELEVATE-TN: Acalabrutinib, Obinutuzumab and Chlorambucil in Treatment naïve CLL (clinicaltrials.gov) - P3 | N=535 | Active, not recruiting | Sponsor: Acerta Pharma BV | Unknown status ➔ Active, not recruiting | Trial completion date: Jul 2021 ➔ Sep 2025

Enrollment closed • Monotherapy • Trial completion date • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Oncology • CD20 • CD5 • FCER2

ELEVATE-TN: Acalabrutinib, Obinutuzumab and Chlorambucil in Treatment naïve CLL (clinicaltrials.gov) - P3 | N=535 | Active, not recruiting | Sponsor: Acerta Pharma BV | Trial completion date: May 2020 ➔ Jul 2021

Monotherapy • Trial completion date • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Oncology • CD20 • CD5 • FCER2

ELEVATE-TN: Acalabrutinib, Obinutuzumab and Chlorambucil in Treatment naïve CLL (clinicaltrials.gov) - P3 | N=510 | Recruiting | Sponsor: Acerta Pharma BV | Trial primary completion date: Aug 2019 ➔ Dec 2019

Monotherapy • Trial primary completion date • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Oncology • CD20 • CD5 • FCER2

ELEVATE-TN: Acalabrutinib, Obinutuzumab and Chlorambucil in Treatment naïve CLL (clinicaltrials.gov) - P3 | N=535 | Active, not recruiting | Sponsor: Acerta Pharma BV | Recruiting ➔ Active, not recruiting

Enrollment closed • Monotherapy • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Oncology • CD20 • CD5 • FCER2

ELEVATE-TN: Acalabrutinib, Obinutuzumab and Chlorambucil in Treatment naïve CLL (clinicaltrials.gov) - P3 | N=510 | Not yet recruiting | Sponsor: Acerta Pharma BV

Monotherapy • New P3 trial • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Oncology • CD20 • CD5 • FCER2

Longitudinal Whole Exome Sequencing Identifies Clonal Hematopoiesis and Genomic Heterogeneity as Predictors of Treatment Outcome in Newly Diagnosed Chronic Lymphocytic Leukemia Treated with Chlorambucil-Obinutuzumab (ICKSH 2026) - No abstract available

Clinical • Heterogeneity • Whole exome sequencing • Chronic Lymphocytic Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia

A feline case of intestinal small T-cell lymphoma with prominent lymphoid follicle formation and concurrent intestinal large B-cell lymphoma. (PubMed, J Vet Med Sci) - "Postoperative chemotherapy with chlorambucil and prednisolone was performed. The cat survived for 728 days since initial presentation, with no recurrence of clinical signs or ultrasonographic abnormalities. To the best of our knowledge, this is the first report describing a feline case of intestinal small T-cell lymphoma with prominent lymphoid follicle formation and concurrent intestinal large B-cell lymphoma."

Journal • Anorexia • B Cell Lymphoma • Hematological Malignancies • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • T Cell Non-Hodgkin Lymphoma

CLL14: Comparison of the Treatments of Obinutuzumab + Venetoclax Versus Obinutuzumab + Chlorambucil in Patients With Chronic Lymphocytic Leukemia (clinicaltrials.gov) - P3 | N=445 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Sep 2021 ➔ Sep 2020

Trial completion date • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Oncology

CLL14: Comparison of the Treatments of Obinutuzumab + Venetoclax Versus Obinutuzumab + Chlorambucil in Patients With Chronic Lymphocytic Leukemia (clinicaltrials.gov) - P3 | N=432 | Not yet recruiting | Sponsor: Hoffmann-La Roche

New P3 trial • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Oncology

CLL14: Comparison of the Treatments of Obinutuzumab + Venetoclax Versus Obinutuzumab + Chlorambucil in Patients With Chronic Lymphocytic Leukemia (clinicaltrials.gov) - P3 | N=445 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Sep 2020 ➔ Aug 2025

Trial completion date • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Oncology

CLL14: Comparison of the Treatments of Obinutuzumab + Venetoclax Versus Obinutuzumab + Chlorambucil in Patients With Chronic Lymphocytic Leukemia (clinicaltrials.gov) - P3 | N=432 | Recruiting | Sponsor: Hoffmann-La Roche | Not yet recruiting ➔ Recruiting

Enrollment open • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Oncology

CLL14: Comparison of the Treatments of Obinutuzumab + Venetoclax Versus Obinutuzumab + Chlorambucil in Patients With Chronic Lymphocytic Leukemia (clinicaltrials.gov) - P3 | N=445 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Trial primary completion date: Nov 2018 ➔ Aug 2018

Trial primary completion date • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology

CLL14: Comparison of the Treatments of Obinutuzumab + Venetoclax Versus Obinutuzumab + Chlorambucil in Patients With Chronic Lymphocytic Leukemia (clinicaltrials.gov) - P3 | N=445 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Recruiting ➔ Active, not recruiting

Enrollment closed • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Oncology

Field-testing the MALT-IPI in a single center real-world cohort of patients with extranodal marginal zone lymphoma. (PubMed, Blood Adv) - "Although it was developed in the context of the IELSG-19 trial exclusively in patients treated with chlorambucil, rituximab or their combination, it is commonly used across virtually all disease settings. Incorporation of autoimmunity identified a small subgroup with inferior PFS and OS but provided limited incremental prognostic power beyond the established index in most patients. Our results support context-specific applicability of the MALT-IPI and highlight autoimmunity as a prognostically relevant factor in a small cohort of patients."

Journal • Real-world evidence • Extranodal Marginal Zone Lymphoma • Hematological Malignancies • Infectious Disease • Lymphoma • Marginal Zone Lymphoma • Oncology

ROS-Activated Peptide-Based Prodrug for Chemoselective Covalent Targeting in Cancer Cells. (PubMed, J Med Chem) - "Herein, we report IRS1, a peptide-based prodrug comprising an integrin-targeting RGD motif, an ROS-responsive thiomorpholine unit, and a chlorambucil-derived covalent warhead for efficient cancer inhibition...IRS1 effectively disrupts membrane integrity, activates extrinsic apoptosis, and induces cancer cell death in vitro. In UM xenograft models, IRS1 shows potent antitumor efficacy with reduced systemic toxicity, highlighting a peptide-reconfiguration strategy for tumor-selective covalent therapeutics."

Journal • Eye Cancer • Melanoma • Oncology • Solid Tumor • Uveal Melanoma

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

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

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