BCL6 rearrangement

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

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

Radiomics signatures based on CE-T1WI and FLAIR sequences have significant value in distinguishing BCL6 rearrangement. The CE-T1WI radiomics model based on VOItumour core and VOIperitumoural oedema are robust markers for identifying BCL6 rearrangement.

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.

The patient was assigned Stage IEA, IPI = 0 and received chemotherapy. This case depicts a very uncommon occurrence of fully localized LBL in a patient of an unusually young age and clinical presentation for this type of lymphoma.

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

P=N/A, N=501, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Oct 2024 --> Oct 2025 | Trial primary completion date: Oct 2024 --> Oct 2025

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.

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.

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

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

P3, N=1000, Active, not recruiting, Hoffmann-La Roche | Trial completion date: Jul 2024 --> Jul 2026 | Trial primary completion date: Jul 2024 --> Jul 2026

Two cases, which transformed from marginal zone lymphomas, carried mutations in KLF2, TNFAIP3 and KMT2D. These findings expand the spectrum of tumors carrying CCND1 rearrangement that may occur as a secondary event in DLBCL mediated by aberrant CSR/SHM and associated with a mutational profile different from that of MCL.

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

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=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

P2, N=27, Recruiting, Patrick C. Johnson, MD | Not yet recruiting --> Recruiting | Trial completion date: Sep 2029 --> Mar 2029 | Trial primary completion date: Sep 2024 --> Mar 2025

The pediatric to YA transition is characterized by decreasing frequency in BL and increasing genetic heterogeneity of MYC-R BCL, with emergence of DH-BCL with MYC and BCL6-R. FISH to evaluate for BCL2 and BCL6 rearrangements is likely not warranted in the pediatric population but should continue to be applied in YA BCL.

P1/2, N=50, Recruiting, 2seventy bio | Trial primary completion date: Dec 2023 --> Aug 2024