IGH mutation

P2/3, N=456, Not yet recruiting, Hemato-Oncologie voor Volwassenen Nederland (Hovon) Stichting

CLL in Türkiye demonstrates region-specific immunogenetic features while preserving established clinico-biological correlations. Integration of IGHV status, cytogenetics, and BCR stereotypy may improve risk stratification in underrepresented populations.

P1, N=15, Recruiting, Dana-Farber Cancer Institute | Trial completion date: Mar 2028 --> Jul 2028

Our analyses show that more epigenetic states are present among CLL neoplasms than are captured by the clinical classification system. Our approach can be used to generate continuous metrics of epigenetic states for other neoplasms.

Objective: This study aimed to investigate the clinical significance of measurable residual disease (MRD) in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) treated with ibrutinib plus fludarabine, cyclophosphamide, and rituximab (iFCR) regimen. Furthermore, the ibrutinib maintenance strategy can be adjusted based on the BM-MRD level at 2 years. Monitoring PB-MRD dynamically was crucial in detecting MRD conversion and progression.

In parallel, targeted therapies such as Bruton tyrosine kinase (BTK) inhibitors and venetoclax-based combinations have transformed the management of symptomatic CLL, raising renewed interest in whether early intervention might favorably alter the natural history of biologically high-risk disease...Finally, we outline future research priorities, including refined genomic stratification, minimal residual disease-driven (MRD)-driven approaches, and combination targeted therapies currently under investigation. Despite renewed interest in preemptive treatment, available evidence supports continued observation for asymptomatic patients outside clinical trials.

Specific proteins and phosphopeptides identified here, upon further validation, may serve as biomarkers for early intervention in UM‑CLL. More broadly, our study demonstrates the value of integrated proteomic and phosphoproteomic profiling which may lead to refining risk stratification and advancing understanding of the complex biology underlying CLL progression.

Despite molecular features associated with a favorable prognosis, the severity of his presentation prompted the initiation of therapy after the exclusion of alternative etiologies. This case highlights the diagnostic and therapeutic uncertainty created by atypical symptomatic presentation of CLL and the prognostic ambiguity of IGHV3-21 CLL requiring cautious interpretation.

P1/2, N=25, Not yet recruiting, AstraZeneca AB

Acalabrutinib-based regimens, either as monotherapy or combined with obinutuzumab, emerged as the most effective strategies for progression-free survival, followed by other BTK inhibitors and venetoclax-based combinations. Chlorambucil- and Fludarabine-containing regimens ranked lowest...Overall, heterogeneity was low, model fit was robust, and no statistical evidence was detected. These findings support targeted agents as the preferred first-line treatment for IGHV-U CLL and provide a quantitative framework to guide regimen selection while highlighting the need for head-to-head trials and long-term follow-up to optimize treatment sequencing.

These findings indicate that the Leader assay provides a more reliable assessment of SHM status, with higher concordance with SS. Although the FR1 assay may offer additional information regarding clonal patterns, its results should be interpreted cautiously. Given the limited sample size, further studies are warranted to validate these findings. Overall, the Leader assay appears to be more suitable as a primary tool for SHM evaluation, with FR1 results serving a complementary role when interpreted in clinical context.