IGH (Immunoglobulin Heavy Locus)

P2, N=30, Recruiting, Mayo Clinic | Trial completion date: Nov 2025 --> Jan 2027 | Trial primary completion date: Nov 2024 --> Jan 2027

Interestingly, we found a higher CD4+HLA-G+ percentage in the group with unmutated immunoglobulin heavy chain variable region (IGHV) genes compared to the group with mutated IGHV gene after 48 h co-culture. In summary, increasing evidence has revealed that, in addition to HLA-G expressed on tumor cells, intercellular transfer of HLA-G among cancer cells and immune cells through trogocytosis plays important roles in mechanism of immune escape, disease progression and poor clinical outcome.

Based on our experience, SHM status can be achieved by routine NGS testing. Our first-year mutated-versus-unmutated test results are reasonably close to what is reported in the literature, supporting the effectiveness of this assay. The majority (66.6%) of QNS samples were due to lack of evidence of clonality in CLL samples.

Responses are durable, with 89%, 87%, and 77% 4-yr PFS in all-comer, uIGHV, and TP53 aberrant pts. Our data support further study of AVO for pts with TN high risk CLL in GCLLSG CLL16 and future trials.

This study supports the use of MRD testing to guide duration of Ven / Obin therapy in the 1L setting. Early discontinuation of Ven/Obin for pts who are uMRD6 at C9 achieves similar PFS to pts who completed 12C of Ven/Obin and have uMRD5 status before entering TFO. In this study, concordance rate between PB and BM was relatively low (approximately two-thirds concordance) at 10-6 (C9) and 10-5 (C12) sensitivities.

P1/2, N=265, Recruiting, National Cancer Institute (NCI) | Suspended --> Recruiting

This review focuses on recent insights into the understanding of CLL biology. We also consider the translation of these findings into the development of risk-adapted and targeted therapeutic approaches.

However, it should be noted that MRD diagnostics for clinical treatment protocols has to be accompanied by regular international quality control rounds to ensure the reproducibility and reliability of the MRD results. This is available by the EuroMRD network ( https://euromrd.org ), a subgroup of ESHLO ( https://eslho.org ).

This study identified significant deficiencies in six functionally distinct DC subsets in blood of untreated CLL (UT-CLL) patients and selective normalization of pDCs in response to acalabrutinib (a Bruton tyrosine kinase inhibitor) therapy...Regarding clinical parameter, cDC subset deficiencies are associated with adverse prognostic indicators of disease progression, including IGHV mutation, CD49d, CD38, and ZAP-70 status. Importantly, UT-CLL patients with shared DC subset deficiencies had shorter time-to-first treatment (TTFT), uncovering a profound alteration in innate immunity with the potential to instruct therapeutic decision-making.

IGHM may be the key contributors to the prognostic differences in HPV-associated OPSCC. This nomogram model was able to accurately predict the prognosis of patients.

Tailored chemo-free regimens can be selected based on age, comorbidities, IGHV status, and cytogenetic abnormalities to optimize treatment outcomes while considering different response spectra.

This is the first case in the literature of TFE3-rearranged RCC with osseous metaplasia on bone mass densitometry scan and the fourth case of TFE3-rearranged RCC with osseous metaplasia. The patient is to be treated as a high-risk patient and to be monitored closely for recurrence of malignancy, as indicated in the EAU guidelines.

IGLL5, MYD88, and KMT2D mutations were enriched in Taiwanese CLL, and co-occurrence of MYD88 mutations with KMT2D or/and IGLL5 mutations was associated with a poorer prognosis.

P2, N=401, Active, not recruiting, Stichting European Myeloma Network | Trial completion date: Feb 2025 --> Feb 2026 | Trial primary completion date: May 2024 --> Jun 2025

Finally, the present study suggested the log Firmicutes/Bacteroidota ratio as a novel intestinal microbiome signature associated with a shorter time to first treatment in individuals with CLL. The findings indicate that oral and gut microbial diversity in CLL might point to the inflammatory-related modulation of the clinical course of the disease.

Given P53's function as a redox-sensitive transcription factor, and insulin's role as a crucial regulator of energy metabolism, their indirect interplay with mt-circRNAs could influence cellular outcomes. However, due to limited attention and infrequent data availability, it is advisable to conduct more thorough investigations to gain a deeper understanding of the functions of mt-circRNA.

P=N/A, N=6000, Recruiting, AstraZeneca | Trial completion date: Dec 2027 --> Mar 2028 | Trial primary completion date: Dec 2027 --> Mar 2028

This study demonstrated high ORR in acalabrutinib-treated Chinese patients with R/R CLL with no unexpected safety concerns. This trial is registered on ClinicalTrials.gov (NCT03932331).

In addition, the IGHV genotyping performed on gDNA revealed a rare case with multiple rearrangements. The present data from IGHV genotyping will help in choosing the proper treatment for the benefit of Bulgarian CLL patients.

The patient received bendamustine and rituximab as chemotherapy, which rapidly improved the anemia and splenomegaly and reduced atypical lymphocytes. An autopsy revealed that the tumor had invaded several organs including the pancreas, and immunohistochemistry was positive for CD163, leading to the diagnosis of HS. Furthermore, the specimens of SMZL and HS were positive for IgH gene reconstitution, and exome analysis showed genetic abnormalities in 226 genes including CARD11, suggesting that the SMZL and HS had the same origin.

New treatment modalities, such as pirtobrutinib, lisocabtagene maraleucel, and ongoing studies combining BTK inhibitors with venetoclax, raise new questions on the significance of prognostic factors of survival for patients with CLL. Testing for prognostic biomarkers will remain relevant to identify patients who may have increased benefit from novel therapeutic strategies, such as combination therapies and novel agents. Patients with high-risk disease should be encouraged to participate in clinical trials.

Care must be taken in the molecular diagnostic work-up of patients with typical HCL but without the BRAF V600E to include investigation of these uncommon mechanisms. Identification, functional characterization, and reporting of further such patients is likely to provide insights into the pathogenesis of HCL and enable rational selection of targeted inhibitors in such patients if required.

These clinical cases emphasize the challenges in diagnosing BNS. Based on the findings, biopsy is recommended for accurate identification of the clonal relationship and MYD88 mutation status.

Upregulation of PD-L1-PD-1 pathway may also promote lymphomagenesis in CVID. These abnormalities need to be explored as prognostic or predictive markers of CVID-associated NHLs by large multi-centric studies.

P=N/A, N=6000, Recruiting, AstraZeneca | Trial completion date: Dec 2026 --> Dec 2027 | Trial primary completion date: Dec 2026 --> Dec 2027

Gene ontology and pathway analysis revealed the potential involvement of these dysregulated peptides in HCC. These findings provide valuable insights into the molecular basis of HCC and may contribute to the development of improved diagnostic methods and therapeutic targets for HCC.

The findings of this study have contributed to the understanding that the chiral metabolome plays a role in the poor prognosis observed in an exceptionally rare patient cohort. The findings include elevated D-amino acid incorporation in the IgH group, the emergence of several unknown, potentially enantiomeric, metabolites, and insights into metabolic pathways that all warrant further exploration.

Specifically, the successful FR3-JH detection was associated with significantly worse OS (p < 0.001) and PFS (p < 0.001). PCR patterns of complete IgH rearrangement using the BIOMED-2 protocol are clinically meaningful indicators for prognostic stratification of DLBCL patients.

Moreover, we present and discuss new scoring systems that were elaborated and validated in the era of new drugs. In routine clinical practice, the application of an extensive genomic work-up with validated prognostic markers could improve the identification of "very high-risk" CLL patients who could benefit from novel, more effective targeted treatments.

CIT may lead to increase in IgA levels. Hypogammaglobulinemia is more common in patients with progressive CLL and unmutated IGHV or TP53 dysfunction.

P1/2, N=11, Completed, Takeda | Active, not recruiting --> Completed | N=68 --> 11 | Trial completion date: Jan 2027 --> Jul 2024 | Trial primary completion date: Dec 2024 --> Dec 2023

P2, N=234, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Jul 2024 --> Jul 2025 | Trial primary completion date: Jul 2024 --> Jul 2025

In the CLL14 study, patients with previously untreated CLL and coexisting conditions were randomized to 12 cycles of Ven-Obi (n=216) or chlorambucil-obinutuzumab (Clb-Obi, n=216). The sustained long-term survival, uMRD and QoL benefits support the use of one-year fixed-duration Ven-Obi in CLL. NCT02242942, EudraCT 2014-001810-24.

In the future, next-generation sequencing (NGS)-based processing of liquid biopsy samples can overcome the limitations resulting from the spatial heterogeneity of lymphoid malignancies. Over the long term, this identification could lead to early patient selection and alternative treatment strategies, ultimately leading to improved prospects for cure.

Finally, we underscore the necessity of aggregating real-world data, adopting a global perspective, and ensuring patient engagement. Taken together, we argue that precision medicine is not the mere application of precision diagnostics and accessibility of precision therapies in CLL but encompasses various aspects of the patient journey (e.g., lifestyle exposures and comorbidities) and their preferences toward achieving true personalized medicine for patients with CLL.

Most cases of salivary gland amyloidosis are AL type, but a minority are ATTR. Therefore, proteomics-based typing remains essential for treatment and prognosis.

The normative daunorubicin (40 mg/m2 on days 1-3) and cytarabine (80 mg/m2 on days 1-7) regimen combined with venetoclax (400 mg on days 1-7) and rituximab (375 mg/m2 on day 0) was used as induction chemotherapy. The presence of a complex karyotype was associated with the poorest prognosis, and patients who received venetoclax often exhibited an improved prognosis. In conclusion, the combination of venetoclax and rituximab improves the prognosis of patients with concurrent AML and untreated CLL.

This study constitutes the first attempt at using NGS to assess the mutational status of the IGHV gene in Lebanese patients. Further investigation could help identify new subsets and classifications. Additional studies combining cytogenetic analysis and molecular testing may prove useful for a better understanding of the characteristics of CLL patients, leading to optimal personalized care.

Our results indicated the most critical regions in the IGH enhancers and provided new insights into the current understanding of the role of IGH enhancers in B-cell NHL. As such, this study forms a basis for development of potential therapeutic approaches.

P1/2, N=3, Suspended, National Cancer Institute (NCI) | N=265 --> 3

Our results suggest that C5 could be a potential biomarker for CRC diagnosis. Further validation studies will aid the application of these new potential biomarkers to improve CRC diagnosis and patient care.

Sequencing analysis for immunoglobulin heavy variable genes indicated a common B-cell origin of the two sets of lymphoma cells. This case report and literature review provide new insights into PBL tumorigenesis.