Chronic Lymphocytic Leukemia

P2, N=223, Recruiting, Merck Sharp & Dohme LLC | Trial completion date: Apr 2027 --> May 2029

There was also evidence of dose-dependent effects at low miR-155 levels. Altogether, our findings indicate that the deficiency of both ICOSL and MHC-I activity, driven by high levels of miR-155, may be causative in the failure of the host immune system to recognize and eliminate malignant B cells.

These observations suggest that statins as single agent do not slow and may even modestly stimulate progression of CLL.

P1, N=30, Recruiting, National Cancer Institute (NCI) | Trial primary completion date: Dec 2025 --> Jun 2027 | Trial completion date: Dec 2025 --> Jun 2027

In the recent 2024 ESMO guidelines, the combination of venetoclax and ibrutinib was listed as one of the first-line treatment options for CLL patients. Currently, several ongoing clinical trials are investigating the rationale for the combination of BCL2is and BTKis. In this review, we discuss the recent advancements in the field of co-therapy with BTKis and BCL2is.

P1/2, N=424, Recruiting, Genmab | N=304 --> 424

This genetic anomaly frequently coexists with trisomy 12. Preliminary data suggest that these cases may have a shorter TTFT, though larger cohorts are needed for validation.

The inducible ablation of PDL1 on macrophages was sufficient to improve immune control of MYC-expressing lymphoma in a syngeneic immunocompetent model. These results implicate the macrophage/CD8+ T-cell axis as a key pathogenetic determinant and immunotherapeutic target in a subset of DLBCL patients with poor prognosis.

it is the first study to indicate that PARK-2 rs1801474 and rs1801334 SNPs carrying significant risk factors of NHL and it is correlated to some clinical pathological parameters may be due to down regulation of PARK-2 gene expression.

Ex vivo pharmacologic profiling suggested that during pirtobrutinib therapy, peripheral blood mononuclear cells (CLL cells) became resensitized to ibrutinib and other targeted agents. Combination therapy, including ibrutinib and venetoclax, was effective regardless of genomic background and even after relapse from pirtobrutinib monotherapy.

P=N/A, N=55, Active, not recruiting, Canadian Cancer Trials Group | Trial completion date: Jan 2025 --> Jan 2026

P3, N=250, Recruiting, BeiGene | Not yet recruiting --> Recruiting

This case illustrates that nucleolated lymphocytes can be observed in the peripheral blood smear of patients with EMZL. These findings expand the differential diagnosis of circulating nucleolated lymphocytes in the blood.

Initially approved by the FDA in 2001 for the treatment of B-cell chronic lymphocytic leukemia (B-CLL), alemtuzumab's therapeutic applications have expanded to various hematologic malignancies, including lymphoma, acute leukemia, myelodysplastic syndromes (MDS), aplastic anemia (AA), graft-versus-host disease (GVHD), and chimeric antigen receptor T-cell (CAR-T) therapy. This review evaluates the efficacy and safety of alemtuzumab in these conditions, aiming to synthesize current evidence and provide guidance for clinical practice to optimize the use of alemtuzumab in the treatment of these diseases.

Analysis of NK cell activation, cytokine release, proliferation and anti-leukemia reactivity demonstrated that MIC12 induced superior target cell killing and NK cell expansion compared to Fc-optimized CLEC12A antibody, with efficacy being dependent on target antigen binding. Our results show that novel immunocytokines with conditional IL-15 activity are capable of inducing potent NK cell responses against AML cells and identify MIC12 as promising therapeutic candidate for leukemia treatment.

P1, N=144, Recruiting, Ascentage Pharma Group Inc. | N=35 --> 144 | Trial completion date: Jun 2026 --> Jun 2027 | Trial primary completion date: Mar 2025 --> Oct 2025

P3, N=82, Active, not recruiting, Incyte Corporation | Recruiting --> Active, not recruiting | Trial completion date: Dec 2026 --> Apr 2027 | Trial primary completion date: Dec 2025 --> Apr 2026

Thus, we suggest that environmental SAg-exposure promotes the accumulation of pseudo-exhausted T cells, which induce/sustain tumour cell activation, not counteracted by ibrutinib. Our study critically helps understand the chronic inflammatory milieu in CLL patients, with implications for infection morbidity, disease aetiology and future interventions.

P2, N=35, Recruiting, Fred Hutchinson Cancer Center | Trial completion date: Mar 2027 --> Sep 2027 | Trial primary completion date: Mar 2025 --> Nov 2025

While we could consistently define the sensitivity of a tumor cell to a particular BH3 mimetic drugs using intact cells, this was not reliable with permeabilized cells. These studies emphasize the need to carefully evaluate assays on permeabilized cells undertaken with inhibitors of the pro-survival BCL2 proteins.

Bayesian NMAs found zanubrutinib to be the most efficacious treatment for high-risk patients, with significantly reduced risk of progression or death compared with ibrutinib (hazard ratio [95% credible interval (CrI)]: 0.49 [0.31, 0.78]), acalabrutinib (0.55 [0.32, 0.94]), and bendamustine + rituximab or idelalisib + rituximab (BR/IR) (0.12 [0.05, 0.26]). Rates of response also demonstrated trends favoring zanubrutinib compared to acalabrutinib, with significant results compared to ibrutinib. The NMA suggests that the most efficacious BTKi for patients with high-risk R/R CLL is zanubrutinib.

Additionally, an interactive application is available via Streamlit, and the source code is open access on GitHub. Despite limitations in dataset size and external validity, ML models show promise for personalized survival predictions in CLL, especially for MYC-positive cases, underscoring the potential for further model refinement to enhance clinical usability.

In addition to established therapeutic targets such as CD3, CD20 and CD38, our analysis highlights BAFF-R and CD39 in HL, CD25 in MM, CD27 in CLL, CD80/86 in DLBCL, and CCR2 in FL and MZL as promising candidates for therapeutic inhibition. Our findings provide further support for the potential of human genetics to guide the identification of drug targets and address a productivity-limiting step.

Rates of AEs, serious AEs, and events of clinical interest were similar between acalabrutinib-containing arms and consistent with the known safety profiles of acalabrutinib and obinutuzumab. Efficacy and safety of acalabrutinib-containing arms were maintained, with longer PFS in both acalabrutinib arms vs chlorambucil-obinutuzumab including in patients with high-risk features.

P2, N=133, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Mar 2025 --> Mar 2026

P1/2, N=45, Not yet recruiting, Tongji Hospital

P2, N=60, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Apr 2025 --> Apr 2028 | Trial primary completion date: Apr 2025 --> Apr 2028

P1, N=18, Recruiting, Catapult Therapeutics | Trial completion date: Apr 2025 --> Apr 2027 | Trial primary completion date: Jan 2025 --> Jan 2027

P2, N=41, Active, not recruiting, Ohio State University Comprehensive Cancer Center | Trial completion date: Dec 2024 --> Dec 2025

P2, N=42, Active, not recruiting, Jennifer Woyach | Trial completion date: Dec 2024 --> Aug 2025

P1, N=36, Active, not recruiting, Synthekine | Recruiting --> Active, not recruiting

CLL cell-derived exosomes inhibited hematopoietic progenitor proliferation, hindering the supportive effect of monocyte-derived fibrocytes. Together, our findings suggest that CLL cell-derived exosomes disrupt the immune and hematopoietic systems and contribute to disease progression in patients with CLL.

P=N/A, N=250, Active, not recruiting, AstraZeneca | Recruiting --> Active, not recruiting

Median overall survival (OS) was 2.2 years once DR developed despite frequent initial responses to non-covalent BTKis or cellular therapy in the cohort. Patients with DE CLL demonstrated favorable survival (median OS not reached) and durable response to subsequent therapy.

P1, N=39, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Mar 2025 --> Mar 2026 | Trial primary completion date: Mar 2025 --> Mar 2026

Also, a combination of markers such as CD19, CD20, CD5, CD23, CD79b, FMC7, SmIg, CD22, CD43, CD200, the ratio CD19/CD20 may be a potential differentiating modality for typical CLL/SLL, atypical CLL/SLL, and MCL. Adding the CD19/CD20 ratio, CD43, and CD200 indicators to the MSS indicators could be potentially accurate diagnostic and differential diagnosis modality for typical CLL/SLL, atypical CLL/SLL, and MCL.

P1, N=45, Completed, Janssen Research & Development, LLC | Active, not recruiting --> Completed

P2, N=260, Active, not recruiting, City of Hope Medical Center | Trial completion date: Dec 2024 --> Apr 2025

P1/2, N=7, Terminated, Conjupro Biotherapeutics, Inc. | Suspended --> Terminated; Business reasons

These findings provide new insights into the mechanisms by which SF3B1 mutations reshape the pre-mRNA splicing landscape and drive disease pathogenesis in MDS. Furthermore, they underscore the potential of UBA7 as a biomarker to stratify SF3B1-mutant MDS and CLL patients, offering a refined approach for risk assessment and highlighting opportunities for targeted therapeutic interventions.

This prospective postmarketing surveillance study confirms the effectiveness and manageable safety profile of alemtuzumab for Japanese patients with relapsed/refractory CLL.

Our findings highlight the altered expression of key cytotoxicity markers on γδ T cells in CLL, suggesting their potential role in disease progression and as a therapeutic target. In particular, the use of anti-LAG-3 antibodies seems promising.