P3, N=698, Active, not recruiting, Novartis Pharmaceuticals | Trial primary completion date: Feb 2027 --> Aug 2024

P1, N=76, Recruiting, Daewoong Pharmaceutical Co. LTD.

P2, N=3, Active, not recruiting, M.D. Anderson Cancer Center | N=24 --> 3 | Trial completion date: Jun 2024 --> Dec 2025

P2, N=62, Active, not recruiting, Guangzhou Lupeng Pharmaceutical Company LTD. | Recruiting --> Active, not recruiting

P2, N=76, Active, not recruiting, Seoul National University Hospital | Recruiting --> Active, not recruiting

P1, N=23, Not yet recruiting, City of Hope Medical Center

P1/2, N=38, Completed, Prof. Dr. Clemens Schmitt | Active, not recruiting --> Completed | Trial primary completion date: Jun 2024 --> Nov 2024

P1, N=25, Completed, Dizal Pharmaceuticals | Recruiting --> Completed | Trial primary completion date: Aug 2024 --> May 2024

The complete response rate was 25.0% and 42.9% in the lenalidomide 15- and 20-mg cohorts, respectively. Due to acceptable toxicity and preliminary efficacy, the lenalidomide 20-mg dose was selected for further investigation.

P1, N=20, Not yet recruiting, University of Miami

P3, N=194, Active, not recruiting, Principia Biopharma, a Sanofi Company | Recruiting --> Active, not recruiting

P1, N=25, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Nov 2024 --> Nov 2025 | Trial primary completion date: Nov 2024 --> Nov 2025

P2, N=12, Completed, Bnai Zion Medical Center | Active, not recruiting --> Completed

P2, N=360, Active, not recruiting, ECOG-ACRIN Cancer Research Group | Trial completion date: Mar 2025 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025

P1, N=20, Completed, University Hospital Tuebingen | Active, not recruiting --> Completed

Adverse events were as expected with zanubrutinib; rate of atrial fibrillation was 7.1%. At a median follow-up of 61.2 months, the results supported the initial SEQUOIA findings and suggested that zanubrutinib was a favorable treatment option for untreated patients with CLL/SLL.

AVO was highly active and well-tolerated in patients with previously untreated CLL with high-risk CLL, supporting its use as a new standard of care treatment option.

An Ara-C-containing intensified induction therapy followed by autologous stem cell transplantation (ASCT) is considered a highly effective treatment strategy in younger mantle cell lymphoma (MCL) patients, inducing long-lasting remissions...With the recently published results of the TRIANGLE trial, showing superiority of an ibrutinib-containing immunochemotherapy induction followed by ASCT compared with the standard therapy and, more strikingly, a noninferiority of an ibrutinib-containing regimen without ASCT compared with the standard regimen with ASCT, we consider the addition of ibrutinib to first-line therapy in younger MCL patients as a new standard of care...For patients with TP53 aberrations, ASCT should not be recommended due to potential toxicity and limited efficacy in this high-risk subgroup. Large randomized clinical trials such as ECOG-ACRIN 4151 will help to ultimately clarify the role of ASCT.

Background : Maintenance therapy with the Bruton's tyrosine kinase inhibitor (BTKi) ibrutinib following ibrutinib-containing chemoimmunotherapy with or without high-dose chemotherapy and autologous stem cell rescue (HDT/ASCR) in younger patients (pts) with mantle cell lymphoma (MCL) has demonstrated superior efficacy over standard chemoimmunotherapy with ASCR (Dreyling et al...Concurrent maintenance with rituximab was not used...At 2 years, the PFS rate (95% confidence interval) was 73.5% (35.9, 91.1) in the overall study population, 37.5% (1.1, 80.8) in pts with MRD+, and 88.9% (43.3, 98.4) in pts with MRD-U (MRD based on status at Day 100).Conclusions : Acalabrutinib demonstrated a tolerable safety profile and promising results in maintaining MRD-U, supporting the use of acalabrutinib as maintenance therapy post-HDT/ASCR in pts with MCL. Given the early study closure, the limited sample size, and the need for longer follow-up for PFS, additional investigations may provide further insights into the role of BTKi maintenance in the post-HDT/ASCR setting.

Base substitution or indel variants were detected in TP53 (28% of cases), KMT2D (25%), CREBBP (14%), EZH2 (8%), MYD88 (8%), TNFRSF14 (8%), ATM (8%), NOTCH1 (7%), ARID1A (6%), B2M (6%), TNFAIP3 (6%), PIM1 (4%), CD79B (3%), BTK (2%, 97% of which were C481X ibrutinib resistance mutations in cases of CLL), MEF2B (2%), BCL2 (1%), and PLCG2 (1%)...Overall, 75% of FLs harbored a canonical IGH : : BCL2 rearrangement and 86% of MCLs harbored a canonical IGH : : CCND1 rearrangement.Conclusions : This analysis of 3,692 samples demonstrated that the F1H assay platform reliably detects a broad landscape of genomic alterations across a range of mature B-cell lymphoma/leukemia subtypes. By detecting all classes of genomic alterations in a single sequencing reaction, F1H provides an important advantage over single-gene and small-panel molecular tests in an era when the diagnosis, prognosis, and treatment of hematological malignancies increasingly rely on assessing the presence, as well as the absence, of numerous genomic alterations.

Uni- and multi-variate analyses of clinical variables that may be associated with clinical and MRD outcomes are underway.Conclusions : Bendamustine, rituximab and acalabrutinib front-line therapy for WM is safe and well tolerated in a relatively elderly population with a toxicity profile consistent with the utilized drugs and not greater than that seen with BR and Placebo in the randomized ECHO trial in untreated Mantle Cell Lymphoma. Initial clinical results show that this treatment is associated with a very high proportion of CR + VGPRs as well as MRD negativity.

P1/2, N=34, Active, not recruiting, US Oncology Research | N=26 --> 34 | Trial completion date: Jun 2024 --> Jan 2025 | Trial primary completion date: Jun 2024 --> Jan 2025

P1/2, N=24, Active, not recruiting, Acerta Pharma BV | Trial completion date: Dec 2025 --> Apr 2026

P2, N=60, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Jan 2025 --> Jan 2027 | Trial primary completion date: Jan 2025 --> Jan 2027

P1/2, N=58, Not yet recruiting, Eli Lilly and Company

P1, N=45, Active, not recruiting, Janssen Research & Development, LLC | Trial completion date: Dec 2026 --> Apr 2025 | Trial primary completion date: Nov 2024 --> Apr 2025

P1, N=85, Active, not recruiting, Janssen Research & Development, LLC | Trial completion date: Dec 2026 --> Apr 2025 | Trial primary completion date: Apr 2026 --> Apr 2025

P3, N=700, Recruiting, Janssen Research & Development, LLC | Enrolling by invitation --> Recruiting

P1, N=75, Active, not recruiting, Janssen Research & Development, LLC | Trial completion date: Dec 2026 --> Jul 2025

Additionally, high ZAP-70 expression was linked to less cell death in the spleen. Overall, our study enhances understanding of CLL genetics and patient response to ibrutinib and provides a framework applicable to the study of similar drugs.

The phase 3 ASPEN study compared the efficacy and safety of zanubrutinib with ibrutinib in patients with WM. While further investigation is required, this analysis supports the potential use and further exploration of Bruton tyrosine kinase inhibitors to treat PN symptoms in patients with WM. ClinicalTrials.gov: NCT03053440.

P=N/A, N=35, Not yet recruiting, Ono Pharmaceutical Co. Ltd

P2, N=87, Recruiting, BeiGene | Not yet recruiting --> Recruiting

Oral health care providers should include CLL in the differential diagnosis for multiple erythematous papules of the palatal mucosa, particularly in the presence of absolute lymphocytosis. Early recognition of oral manifestations associated with CLL can prompt a timely referral.

The topical application of the drug successfully reduced irritation and toxicity in the skin, and the drug was shown to successfully permeate the stratum corneum and reach the viable skin layers in therapeutic concentrations. Overall, our data encourage the topical application of IBR to treat melanoma, paving the way for future studies in this theme.

P2, N=72, Recruiting, Mayo Clinic | N=45 --> 72

P2, N=35, Active, not recruiting, Weill Medical College of Cornell University | Trial primary completion date: Sep 2024 --> Feb 2025

Lasalocid-A exhibited strong antitumor efficacy in xenograft mouse models, induced disease remission in ibrutinib-resistant lymphomas, and showed synergistic activity with the BCL2 inhibitor venetoclax. This study highlights the potential of inducing MYD88 L265P degradation using small molecules, offering promising strategies for treating lymphomas that harbor the MYD88 L265P mutation.

Clinical trials that studied the combination of the first generation BTKi ibrutinib and V have shown the feasibility and efficacy of the regimen. Given the favorable safety profile and sustained efficacy of acalabrutinib, combination regimens with venetoclax without (AV) or with obinutuzumab [O] (AVO) have been studied in the first line setting, and favorable efficacy and safety have been reported...Patients with significant cardiovascular disease, absorption issues, active bleeding or history of bleeding diathesis or required/currently receiving anticoagulation with warfarin or equivalent vitamin K antagonists were excluded...Clinical responses including uMRD4 at the end of treatment and the safety profile will be assessed. The trial is actively enrolling at Fred Hutchinson Cancer Center/University of Washington.

Emerging long-term data from the cBTKi pivotal trials demonstrated that only a minority of pts can remain on Tx long-term (e.g. 42% of pts were still on ibrutinib [Ibr] at 89-months follow-up [FU] in the RESONATE-2 trial, with 24% having discontinued due to an AE; Barr et al...Pts (aged ≥18 years) are eligible to enroll if they have received ≥6 months of a cBTKi (Ibr, acalabrutinib [Acala], or zanubrutinib [Zanu]) for 1L Tx of CLL and are on a stable dose with a partial response (PR) or complete response (CR), per International Workshop on CLL criteria...Approximately 100 pts are planned for enrollment at around 28 sites in the US. The study is actively recruiting.

Introduction : The combination of venetoclax, the first-generation BCL2 inhibitor, and ibrutinib, a BTK inhibitor, has demonstrated efficacy in patients with chronic lymphocytic leukemia (CLL) (Wierda et al. Other secondary endpoints include PFS as assessed by investigator (INV); CRR by INV; rate of uMRD4 based on flow cytometry; overall response rate by IRC and INV; duration of response by IRC and INV; patient-reported outcomes; and safety and tolerability. Recruitment is ongoing at approximately 230 study sites in 20 countries, including 50 sites in the US, 6 in Brazil, and 15 in Canada.

Patients will receive obinutuzumab 2000 mg IV on C1D1-2, followed by glofitamab step-up dosing of 2.5 mg IV on C1D8, 10 mg on C1D15, and 30 mg on day 1 of C2-12 (21-day cycles). In the current trial we evaluate a regimen which we anticipate will be tolerable and highly active in R/R MCL, with the potential for MRD-guided limited-duration therapy. The trial is currently open for enrollment at UCSF and is expected to open at multiple centers through the University of California Hematologic Malignancies Consortium.