BCL2 rearrangement

No abstract available

High-grade B-cell lymphomas are subclassified based on morphologic and genetic features. There are differences in the nomenclature and definition of these lymphomas in the WHO-5 and ICC classifications. Distinguishing HGBLs from other mature B-cell lymphomas and B-LBL/ALL is critical so that patients receive appropriate treatment.

P1/2, N=38, Completed, Prof. Dr. Clemens Schmitt | Active, not recruiting --> Completed | Trial primary completion date: Jun 2024 --> Nov 2024

Base substitution or indel variants were detected in TP53 (28% of cases), KMT2D (25%), CREBBP (14%), EZH2 (8%), MYD88 (8%), TNFRSF14 (8%), ATM (8%), NOTCH1 (7%), ARID1A (6%), B2M (6%), TNFAIP3 (6%), PIM1 (4%), CD79B (3%), BTK (2%, 97% of which were C481X ibrutinib resistance mutations in cases of CLL), MEF2B (2%), BCL2 (1%), and PLCG2 (1%)...Overall, 75% of FLs harbored a canonical IGH : : BCL2 rearrangement and 86% of MCLs harbored a canonical IGH : : CCND1 rearrangement.Conclusions : This analysis of 3,692 samples demonstrated that the F1H assay platform reliably detects a broad landscape of genomic alterations across a range of mature B-cell lymphoma/leukemia subtypes. By detecting all classes of genomic alterations in a single sequencing reaction, F1H provides an important advantage over single-gene and small-panel molecular tests in an era when the diagnosis, prognosis, and treatment of hematological malignancies increasingly rely on assessing the presence, as well as the absence, of numerous genomic alterations.

P2, N=168, Active, not recruiting, Miltenyi Biomedicine GmbH | Trial completion date: Jul 2027 --> Jul 2029

In this review, we provide an update of HGBL and its subgroups, focusing on their clinicopathologic features, diagnosis, molecular genetic features, and pathogenesis. Our diagnostic approach and caveats for differential diagnosis are also discussed with an emphasis on the differential diagnosis with B lymphoblastic leukemia/lymphoma.

P2, N=54, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Oct 2024 --> Oct 2025

P2, N=132, Recruiting, National Cancer Institute (NCI) | Trial completion date: Mar 2029 --> Mar 2030 | Trial primary completion date: May 2025 --> May 2026

Our results suggest that an integrated NGS strategy should not replace FISH or be routinely used in the workup to detect the clinically relevant rearrangements in HGBCL. It may serve as a complement to FISH testing when FISH shows negative results.

P1/2, N=54, Completed, Incyte Corporation | Active, not recruiting --> Completed

Our study demonstrates that our local population has similar clinicopathological and prognostic characteristics of DLBCL as compared to global findings. It also highlights the limitations of R-CHOP(-like) regimens in contemporary DLBCL management and therefore an ongoing need for improved therapeutic strategies.

P2, N=37, Recruiting, David Bond, MD | Trial primary completion date: Dec 2024 --> Dec 2025

P1/2, N=112, Recruiting, Shanghai AbelZeta Ltd. | Phase classification: P1b/2 --> P1/2 | N=72 --> 112 | Trial completion date: Mar 2027 --> Dec 2027 | Trial primary completion date: Mar 2027 --> Oct 2025

Introduction : High grade B-cell lymphomas with MYC, BCL2 and/or BCL6 rearrangements (R) are a group of aggressive lymphomas with poor prognosis when treated with R-CHOP and generally present at advanced stage with a high risk of CNS relapse...Indeed, there was no clear impact of CNS prophylaxis/IT-chemotherapy as relapses were distributed equally between those who did or did not receive prophylaxis. Larger multicenter studies dedicated to this unique population is warranted and our study supports the ongoing separation of MYC/BCL6-R for further research purposes.

P2, N=39, Recruiting, University of Rochester | Trial completion date: Jul 2024 --> Jul 2026 | Trial primary completion date: Jul 2024 --> Jul 2026

Carcinomatous meningitis is a condition in which cancer cells metastasize to the meninges without involving the brain parenchyma; this phenomenon has also been reported in the literature by other terms like "leptomeningeal meningitis," "leptomeningeal carcinomatosis," "leptomeningeal metastasis," or "neoplastic meningitis." This form of CNS involvement has been described as an infrequent complication with the trajectory of this aggressive lymphoma. We report an illuminating case of a 63-year-old male diagnosed with double-hit lymphoma, which was complicated by fatal carcinomatous meningitis.

CNS relapse in DZsig-negative GCB-DLBCL was rare (2-year risk 1.4%; P=.04 versus DZsig+) and exclusively parenchymal. Altogether, the CNS relapse risk in HGBCL-DH-BCL2 is lower than previously reported and DZsig refines risk stratification in GCB-DLBCL.

The rare, but difficult, diagnostic classification HGBL (NOS) remains a diagnosis of exclusion with limited data on an optimal clinical approach. The days of talking loosely of double and triple hit lymphoma are numbered as this review synergises the current data on biology, prognosis, and therapies in HGBL.

No abstract available

P2, N=24, Active, not recruiting, Northwestern University | Recruiting --> Active, not recruiting

P2, N=32, Recruiting, Dipenkumar Modi | Trial completion date: Jun 2025 --> Nov 2028 | Trial primary completion date: Sep 2024 --> Nov 2027

No abstract available

Individual genomic features of LBCL cases may predict for development of disease progression in newly diagnosed patients treated with standard therapies, as well occur at higher frequencies in cases of disease progression based upon geographic region and/or cell of origin status. These novel findings support efforts to evaluate genomic features as biomarkers for response to specific therapies in subsets of LBCL patients who experience disease progression, which may lead to discovery of more effective treatment options.

However, we observed a subgroup of patients classified as BN2, both in localized and disseminated TLBCL, suggesting a degree of genetic heterogeneity in the TLBCL genetic profile. TLBCL has a distinctive genetic profile similar to PCNSL, supporting its recognition as a separate entity from DLBCL and might provide information to devise targeted therapeutic approaches.

P2, N=71, Active, not recruiting, The Lymphoma Academic Research Organisation | Recruiting --> Active, not recruiting

P1/2, N=225, Recruiting, Novartis Pharmaceuticals | Trial completion date: Jun 2027 --> May 2028

P2, N=30, Active, not recruiting, Kite, A Gilead Company | Trial primary completion date: Mar 2026 --> Sep 2024

We finally confirmed the utility of the scoring system previously proposed by Khanlari to distinguish HGBCL cells from B lymphoblasts of B-ALL. In conclusion, we described a distinct immunophenotypic portrait of HGBCL cells and proposed a strategy to differentiate these cells from other aggressive B lymphoma entities in biological samples.

P2, N=60, Recruiting, Juventas Cell Therapy Ltd. | Trial primary completion date: Jun 2024 --> Dec 2024

P2, N=41, Recruiting, Mayo Clinic | N=62 --> 41

P1, N=24, Completed, Juno Therapeutics, a Subsidiary of Celgene | Active, not recruiting --> Completed | N=80 --> 24 | Trial completion date: Jun 2024 --> Feb 2024 | Trial primary completion date: Jun 2024 --> Feb 2024

P2, N=27, Active, not recruiting, Takeda | N=265 --> 27 | Recruiting --> Active, not recruiting

Immunophenotypically, the cases were predominantly GCB, in contrast to older adults (61%). In summary, we showed that molecular findings identified in the PCNSLs of the older patients were only sparingly present in pediatric and young adult patients.

Furthermore, because one IGH allele is already disrupted by the existing BCL2 rearrangement, the MYC rearrangement architecture in HGBCL-DH-BCL2 likely reflects selective pressure to preserve both BCL2 and B cell receptor expression. These data provide new mechanistic explanations for the distinct patterns of MYC rearrangements observed across different lymphoma entities.

P1/2, N=29, Recruiting, Fondazione Matilde Tettamanti Menotti De Marchi Onlus | Not yet recruiting --> Recruiting

This study reports a rare case of TdT positive "double hit" HGBL following the treatment of concurrent FL/DLBCL and highlights the mutation characteristics. Collectively, this study will help enrich the knowledge of TdT positive "double hit" HGBL transformed from FL/DLBCL.

P1/2, N=150, Recruiting, ImmPACT Bio | N=100 --> 150

P=N/A, N=241, Active, not recruiting, Duke University | Phase classification: P2 --> P=N/A

P2/3, N=422, Recruiting, National Cancer Institute (NCI) | Trial completion date: Mar 2025 --> Mar 2026 | Trial primary completion date: Mar 2025 --> Mar 2026

P1, N=47, Active, not recruiting, Sanofi | Trial completion date: Apr 2024 --> Aug 2024

P1, N=55, Terminated, Fred Hutchinson Cancer Center | Active, not recruiting --> Terminated; Terminated due to slow enrollment and end of funding

P2, N=35, Active, not recruiting, Kite, A Gilead Company | Recruiting --> Active, not recruiting