TEST:

LymphoTrack® Dx IGH Assay

All patients with Philadelphia chromosomes-positive ALL received imatinib concomitantly with chemotherapy...Detection of IgH clonality after second cycle of chemotherapy correlates with inferior survival in B-ALL. Therefore, those patients should be considered for subsequent treatments, such as allogeneic stem cell transplantation or novel monoclonal antibody.

P=N/A, N=250, Completed, Invivoscribe, Inc. | Recruiting --> Completed | Trial completion date: Aug 2024 --> Nov 2024 | Trial primary completion date: Jun 2024 --> Nov 2024

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.

Method : This study involved adult patients aged 19 or older with B-ALL, treated with modified hyper-CVAD (hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone) and allogeneic hematopoietic stem cell transplant (allogeneic-HSCT) at Catholic Hematology Hospital from May 2022 to June 2024...Poor MRD response was defined as > 0.1%, and complete MRD response as < 0.001%, and poor MRD responders were treated with MRD-directed therapy using blinatumomab or next-generation tyrosine kinase inhibitors...Conclusion : Our data suggested all MRD detection methods showed acceptable power and good concordance rates, but the detection power was different between Ph-positive and Ph-negative ALL. We also suggested MRD-directed therapeutic strategies might predict the significant time point of MRD for the prediction of survival outcomes.

Samples derived from cases from both the experimental and the control arm, based respectively on ponatinib followed by blinatumomab and on a combination of imatinib and conventional chemotherapy. While some groups reported a higher predictive prognostic power of IG/TR monitoring, our findings do not confirm these data, also in view of the very low rate of relapses so far observed. Nevertheless, a double-hit strategy may be informative for MRD monitoring and possibly for the distinction between typical/lymphoid Ph+ ALL vs multilineage/CML-like Ph+ ALL.

Figure 1. Circos plot depicts structural variants in ALL patient.

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.

This is the largest study conducted to date in Ireland, profiling risk status in this genetically homogenousnorthern European population. In this study almost one third of TE-MM patients in Ireland present with HRdisease as defined by MMProfilerâ„¢ and validated by independent FISH. The reasons for the high prevalence ofHR-MM at diagnosis is not clear and further in-depth genomic profiling is needed.

"Compared with NGF, NGS exhibits higher sensitivity and reproducibility in MRD detection and can be an effective strategy for MRD monitoring in Chinese MM patients."

P=N/A, N=250, Recruiting, Invivoscribe, Inc. | Not yet recruiting --> Recruiting

We continue to evaluate the clinical significance of SKY92 in combination with MRD testing as a superior prognostic repertoire of testing. These methods will improve risk stratification, and in future aid with risk-adapted therapy approaches.

Our analysis revealed that specific genetic mutations and chromosomal alterations are strongly associated with the disease's course and patient prognosis. Particularly, the presence of unmutated IGHV and TP53 mutations emerged as key indicators of a more aggressive disease course and shorter treatment-free intervals. These findings underscore the critical role of advanced genetic testing in identifying patients who may require more intensive treatment and monitoring.

Overall, NGS of the vitreous demonstrated high sensitivity among conventional diagnostic tests. VRL and CNSL appeared to have both shared and distinct genetic variations, which may suggest site-specific variations from a common origin.

P=N/A, N=250, Not yet recruiting, Invivoscribe, Inc.

Overall, conventional Sanger sequencing and next-generation-sequencing-based clonality and somatic hypermutation analyses gave comparable results. For future use in a routine diagnostic workflow, NGS-based approaches should be evaluated prospectively and an analysis of cost-effectiveness should be performed.

This assay demonstrated excellent test performance characteristics, achieving a sensitivity of 1 out of 100,000 T-cell equivalents for the DNA inputs evaluated and high concordance with orthogonal testing methods. This assay was further utilized to correlate disease burden in several patients, demonstrating its potential utility for monitoring patients with T-cell malignancies.

Here we report a novel UMI-independent method to assess ID in CLL. By applying this approach, we provide evidence that: i) ID prevalently affects M-CLL; ii) patients affected by M-CLL with ID have better outcome than M- CLL cases without ID; iii) ID identifies a subset of M-CLL with specific molecular/biological features and clinicalcharacteristics. IGH, Prognostic factor, Chronic lymphocytic leukemia

A multicenter cohort of 53 consecutive newly diagnosed DLBCL treated with R-CHOP was included in this study... In most DLBCL patients at diagnosis, ctDNA was suitable for IG-based biomarker identification by NGS and was comparable to diagnostic LN biopsies. ctDNA MRD evaluation both at interim and at EOT allowed to predict theoutcome of DLBCL patients. ctDNA MRD can refine the CT/PET-CT-based response.

Future work will aim to evaluate the achievement of MRD negativity based on SKY92 status, and whether this impacts survival. We will continue to profile Irish patients and ultimately, we hope this could lead to a more risk-stratified treatment approach.

A large fraction of NC samples (15%) had evidence of expanded lymphoid clones with SHM. The PTR of the top clone underscores the higher frequency of CE associated with increased age in asymptomatic participants. Clonal expansion of blood cell lineages can also carry genetic or epigenetic alterations that are similar to those associated with non-hematologic cancers.

"Our study demonstrated that MRD assessment by NGS-based Ig clonality assay could be applied in most pediatric B-ALL patients. Normalized post-induction MRD <0.01% was a significant prognostic indicator."

"NGS clonality studies reveal that patients with >1 PTLD lesion often, but not always, demonstrate clonally unrelated lesions, when they are all EBV+, whether these lesions are seeming relapses or present without intervening remissions. Recurrent or multiple EBV- lesions appear to more often represent clonally related lesions, the expectation with lymphomas in immunocompetent hosts. Better understanding of clonal relationship in synchronous or metachronous PTLD cases may eventually lead to different therapeutic approaches in EBV+ and EBV- lesions."

Conclusion : Our study shows that, Ig-based MRD by NGS could be applied in most pediatric B-ALL patients in clinic. Normalization as % of TNC was significant to implicate the MRD as a valuable prognostic.

Higher MRD loads correlated with inferior post-ASCT PFS and OS. The implication of recombined VDJ stereotypes and their impact on ASCT outcomes warrants further investigation.