Chronic Lymphocytic Leukemia

At present, BTK inhibitors, PI3K inhibitors, spleen tyrosine kinase (SYK) inhibitors and BCL-2 inhibitors are the most studied targeted therapeutic drugs for CLL/SLL. This article reviews the research progress of different types of targeted therapeutic drugs in the treatment of CLL/SLL.

P2, N=20, Completed, The First Affiliated Hospital of Soochow University | Recruiting --> Completed | Trial completion date: Jun 2025 --> Apr 2024 | Trial primary completion date: Jun 2023 --> Apr 2024

The median time to hospitalization after infection in CLL patients with a reactive ORF8 response was 12 days versus not reached for patients with a non-reactive ORF8 response with a hazard ratio of 7.7 (95% CI: 2.4-132, p=0.005). These results provide new insight on the monocyte inflammatory response to virus with implications in a broad range of disorders involving monocytes.

Our findings highlight the diverse prognostic influence of genetic aberrations depending on the IGHV status in symptomatic CLL patients receiving first-line CIT. The prognosis of gene mutations and cytogenetic abnormalities needs to be investigated with a compartmentalized methodology, taking into account the IGVH status of patients receiving first-line BTK and/or BCL2 inhibitors.

P1/2, N=48, Recruiting, M.D. Anderson Cancer Center | Not yet recruiting --> Recruiting

This research provides a refined genetic understanding of the CHC-DLBCL connection, opening avenues for targeted therapeutic research and intervention.

P2, N=50, Recruiting, Weill Medical College of Cornell University | Trial completion date: May 2028 --> Dec 2027 | Trial primary completion date: Mar 2027 --> Jan 2025

P1, N=100, Recruiting, Newave Pharmaceutical Inc | Trial completion date: Aug 2024 --> Oct 2025 | Trial primary completion date: Aug 2024 --> Oct 2025

Other explanatory hypotheses include neoplastic stem cells, a genetic predisposition to malignancy, the use of immunosuppressive agents for the treatment for a first neoplasm, viral agents, and modulation of the B-cell system by monoclonal T-cell proliferation (1,5,6,9,10). Regular follow-up is mandatory for all patients with CTCL as well as MF, in order to identify the disease progression but for the timely detection of second malignancies.

P=N/A, N=50, Recruiting, iOMEDICO AG | Trial completion date: Apr 2025 --> Oct 2025 | Trial primary completion date: Apr 2025 --> Oct 2025

P=N/A, N=132, Recruiting, University of Surrey

P2, N=60, Recruiting, Inhye Ahn | Not yet recruiting --> Recruiting | Initiation date: Sep 2024 --> Apr 2024

P=N/A, N=56, Active, not recruiting, Oncology Institute of Southern Switzerland | Trial completion date: Oct 2023 --> Dec 2024

P2/3, N=226, Not yet recruiting, Beijing InnoCare Pharma Tech Co., Ltd.

MNDA was highly expressed in MZL with a potential utility in differential diagnosis between MZL and RLH as well as FL, whereas its value in distinguishing MZL from MCL, CLL/SLL is limited. In addition, MNDA expression in DLBCL was more frequently seen in the non-GCB group and the BCL2/MYC double-expression group, and demonstrated a correlation with CD5, which deserves further investigation. The clinical relevance of MNDA and its correlation with the prognosis of these lymphomas also warrant to be fully elucidated.

Undetectable minimal residual disease at the end of treatment with chemoimmunotherapy or venetoclax-based combination regimens is an independent predictor of improved survival among patients with previously untreated or relapsed/refractory CLL/SLL. The selection of treatment is based on the disease stage, presence or absence of del(17p) or TP53 mutation, immunoglobulin heavy chain variable region mutation status, patient age, performance status, comorbid conditions, and the agent's toxicity profile. This manuscript discusses the recommendations outlined in the NCCN Guidelines for the diagnosis and management of patients with CLL/SLL.

This study confirmed the use of EDR lotion to inhibit hair loss, indicating that the clinical application of EDR lotion may improve the quality of life for patients with cancer and their willingness to undergo treatment.

To better understand the impact of the second-generation BTKi acalabrutinib, we pooled data from 5 prospective clinical studies of acalabrutinib as monotherapy or in combination with obinutuzumab (ACE-CL-001, ACE-CL-003, ELEVATE-TN, ELEVATE-RR, and ASCEND) in patients with higher-risk CLL in treatment-naive (TN) or relapsed/refractory (R/R) cohorts. The safety profile of acalabrutinib-based therapy in this population was consistent with the known safety profile of acalabrutinib in a broad CLL population. Our analysis demonstrates long-term benefit of acalabrutinib-based regimens in patients with higher-risk CLL, regardless of line of therapy.

Despite this immunophenotypic heterogeneity, suppression of B cell development at an early stage consistently occurred within the bone marrow (BM) of STYK1/NOK-tg mice. Overall, we suggest that enforced expression of STYK1/NOK in transgenic mice might significantly predispose BM hematopoietic stem cells (HSCs) towards the development of B-CLL.

P2, N=75, Recruiting, AbbVie | Trial completion date: Jan 2029 --> Jul 2027

P1, N=4, Active, not recruiting, National Cancer Institute (NCI) | Recruiting --> Active, not recruiting | N=12 --> 4 | Trial completion date: Mar 2034 --> Jun 2029 | Trial primary completion date: Mar 2025 --> Jun 2024

P=N/A, N=51, Completed, UNC Lineberger Comprehensive Cancer Center | Recruiting --> Completed | Trial completion date: Nov 2024 --> Sep 2023 | Trial primary completion date: Nov 2024 --> Sep 2023

P=N/A, N=152, Completed, French Innovative Leukemia Organisation | Recruiting --> Completed

Venetoclax was associated with total monthly cost savings versus BTKis, illustrating the economic value of time-limited venetoclax-based regimens in the 2L setting.

P3, N=344, Recruiting, Ascentage Pharma Group Inc. | Not yet recruiting --> Recruiting

Among them, subset #2 with mutated IGHV and poor prognosis, as well as the subset #8 with a high risk of Richter transformation, have been recommended by the European Research Initiative on CLL to be included in clinical reports on IGHV mutational status. This review summarizes the definition, distribution, biological characteristics, and clinical significance of clonality patterns of the BCR in CLL.

P2, N=66, Not yet recruiting, Institute of Hematology & Blood Diseases Hospital, China

P3, N=607, Active, not recruiting, AstraZeneca | Recruiting --> Active, not recruiting

Our findings support ongoing assessment of prognostic tools in CLL treatment evolution. CLL2-BIG (NCT02345863), CLL2-BAG (NCT02401503), CLL2-BIO (NCT02689141), CLL2-BCG (NCT02445131), CLL2-GIVe (NCT02758665), CLL13 (NCT02950051), CLL14-trial (NCT02242942), CLL1 (NCT00262782), CLL8 (NCT00281918), and CLL11 (NCT01010061).

P2, N=30, Active, not recruiting, Swiss Group for Clinical Cancer Research | Trial completion date: Dec 2028 --> Dec 2026 | Trial primary completion date: Apr 2028 --> Apr 2026

P1/2, N=66, Not yet recruiting, National Cancer Institute (NCI)

The covalently bound Ibrutinib molecule, recognized for its ability to inhibit BTK, was used as the query molecule...Covalent docking simulations were applied to the selected small-molecules obtained through text mining from databases. Potent hit molecules capable of inhibiting BTKs through virtual screening algorithms were identified, paving the way for novel therapeutic strategies in the treatment of CLL.

Although the management of treatment with a single continuous agent is easier, the emergence of protein mutations, long-term toxicities and costs are important concerns that favor the use of a fixed duration therapy. In the future, a measurable residual disease (MRD)-guided treatment cessation and MRD-based re-initiation of targeted therapy seems to be a more feasible approach, allowing identification of the patients who might benefit from continuous therapy or who might need a consolidation with BsAbs or CAR T cells to clear the neoplastic clone.

All patients showed improvement of psoriasis after starting the therapy. Our experience supports the effectiveness and safety of biological therapy for psoriasis in patients with a history of cancer or recent onset neoplasia.

The former is considered to be mediated by VDJ-recombination, while the latter by the class switch recombination process. There were no particular features in FL or CLL cases with IGH::5' BCL2 breakpoints compared with those with t(14;18)(q32;q21)/IGH::BCL2 involving the 3' breakpoint cluster regions.

CD20+ T cells were less represented in MBL and CLL patients vs healthy controls, particularly among those with unmutated IGVH gene. The expansion of malignant B cells was accompanied by phenotypic and functional changes in CD20+ T cells, including an increase in follicular helper CD4+ CD20+ T cells and CD20+ Tc1 cells, in addition to the expansion of the TCR Vβ 5.1 in CD4+ CD20+ T cells in CLL.

P1, N=12, Recruiting, National Cancer Institute (NCI) | Trial primary completion date: Mar 2024 --> Mar 2025

P2, N=25, Active, not recruiting, Polish Lymphoma Research Group | Recruiting --> Active, not recruiting | Trial primary completion date: Mar 2024 --> Jun 2024

P1, N=40, Active, not recruiting, Kite, A Gilead Company | Recruiting --> Active, not recruiting | Trial completion date: Jan 2039 --> Feb 2026 | Trial primary completion date: Oct 2024 --> Feb 2026

P2, N=90, Recruiting, Kite, A Gilead Company | Trial completion date: Dec 2027 --> Mar 2025 | Trial primary completion date: Dec 2027 --> Mar 2025

P=N/A, N=89, Recruiting, AbbVie

No abstract available