A Phase Ib/II Study Evaluating the Safety and Efficacy of Mosunetuzumab in Combination With DA EPOCH in Previously Untreated C-Myc Rearrangement Positive High-Grade B Cell Lymphomas

This phase Ib/II clinical trial tests the safety, side effects, and effectiveness of mosunetuzumab with chemotherapy for the treatment of patients with untreated, c-Myc rearrangement positive, high grade B cell lymphoma or diffuse large B cell lymphoma. A monoclonal antibody is a type of protein that can bind to certain targets in the body, such as molecules that cause the body to make an immune response (antigens). Immunotherapy with monoclonal antibodies, such as mosunetuzumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs, such as etoposide, doxorubicin, vincristine, cyclophosphamide and prednisone work in different ways to stop the growth of cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving mosunetuzumab with chemotherapy may be safe, tolerable and/or effective in treating patients with untreated, c-Myc rearrangement positive, high grade B cell lymphoma or diffuse large B cell lymphoma.

Start Date13 Jun 2024

Sponsor / Collaborator

OHSU Knight Cancer Institute

[+2]

NCT05263583

/ Active, not recruitingPhase 2

A Phase 2, Multicenter, Open Label Dose-ranging Study of Sepantronium Bromide in Patients With Relapsed/Refractory c-Myc Rearranged High-grade B-cell Lymphoma (HGBCL)

This is a multi-center Phase 2 study to determine the safety and efficacy of sepantronium bromide (SepB) in adult patients with relapsed or refractory high-grade B-cell lymphoma

Start Date09 Dec 2022

Sponsor / Collaborator

Cothera Bioscience, Inc.

NCT01914718

/ TerminatedPhase 2IIT

Dose-adjusted EPOCH-R in Patients With Diffuse Large B-cell Lymphoma: a Phase II Study

The aim of this study is to evaluate the efficacy and toxicity of dose-adjusted EPOCH-R in patients with MYC positive diffuse large B-cell lymphoma.

Start Date01 Feb 2013

Sponsor / Collaborator

Fudan University

100 Clinical Results associated with C-Myc positive High grade B-cell lymphoma

100 Translational Medicine associated with C-Myc positive High grade B-cell lymphoma

0 Patents (Medical) associated with C-Myc positive High grade B-cell lymphoma

Literatures (Medical) associated with C-Myc positive High grade B-cell lymphoma

01 Apr 2025·Modern Pathology

Cytogenomic and clinicopathological comparison of MYC-positive and MYC-negative High-grade B-cell lymphoma with 11q aberration in the context of other aggressive lymphomas with MYC rearrangement

Article

Author: Rymkiewicz, Grzegorz ; Ott, German ; Pienkowska-Grela, Barbara ; Grygalewicz, Beata ; Szafron, Laura A ; Woroniecka, Renata ; Horn, Heike ; Malawska, Natalia ; Szafron, Lukasz M ; Rygier, Jolanta ; Parada, Joanna ; Nowakowska, Beata ; Blachnio, Katarzyna ; Wojtkowska, Katarzyna ; Bystydzienski, Zbigniew

According to the 2022 WHO classification, High-grade B-cell lymphoma with 11q aberration (HGBCL-11q) is a MYC-negative lymphoma with 11q duplication and terminal deletion as specific chromosomal aberrations for this neoplasm. However, there are a growing number of reports defying this definition describing cases with the co-occurrence of 11q aberration and MYC rearrangement (HGBCL-11q,MYCR). This research has two aims. First, to compare the unique HGBCL-11q,MYCR group of 9 cases with 26 HGBCL-11q cases on chromosomal, mutational and clinicopathological level. The second objective is to investigate the association of the new HGBCL-11q,MYCR group with HGBCL-11q and two other closely related MYC-positive aggressive lymphoma subtypes: Burkitt lymphoma (BL) (n=17) and High-grade B-cell lymphoma, not otherwise specified with MYC rearrangement (n=10). Genetic results were obtained by classical cytogenetics, fluorescence in situ hybridization, microarrays, and whole exome sequencing. In parallel histopathological/ immunohistochemical analyses (HP/IHC) with flow cytometry(FCM), in conjunction with clinical presentation and treatment outcomes are presented. Our findings reveal that HGBCL-11q,MYCR, exists as an independent nosological entity, distinct from BL and HGBCL-11q at the cytogenetic, molecular, and clinicopathological levels, although it contains common features of both lymphoma subtypes. Common features with BL include: MYC rearrangement with the immunoglobulin genes, patterns of secondary chromosomal aberrations like dup(1q), del(17p), high number of MYC and CCND3 mutations. Other BL features are: frequent extranodal abdominal presentation, morphology, GCB cell of origin determined by IHC and FCM, immunophenotypical features such as MYC(+)/LMO2(-) detected by flow cytometric features: CD45(+)^weaker, more cases with CD43(+) and CD44(-) expression, only expression of IgD and IgM heavy chain and CD38(+)^higher overexpression, which correlates with MYC rearrangement assessed by FCM. Similarity to HGBCL-11q includes the existence of 11q aberration, presence of DDX3X, ETS1, GNA13, NFRKB, KMT2D, and the lack of TCF3 and ID3 mutations. Additionally, frequent nodal and tonsillar presentation, morphology, GCB cell of origin, immunophenotypical features with flow cytometry measured CD56(+) expression, associated with NCAM duplication/amplification on 11q, and pathogenesis not associated with Epstein-Barr virus infection. The distinctive chromosomal change of HGBCL-11q,MYCR was the gain or amplification of 3q29. Our cohort of patients with HGBCL-11q,MYCR had similar relapse-free survival to that of patients with HGBCL-11q and BL, if treated with BL-directed regimens.

01 Jan 2024·Neoplasma

Comparative investigation among fluorescence in situ hybridization, DNA- and RNA-sequencing on detecting MYC, BCL2, and BCL6 rearrangements in high-grade B-cell lymphomas

Article

Author: Zhang, Fen ; Liu, Jian ; Chen, Jie ; Cui, Qian ; Liu, Yanhui ; Yan, Jinhai ; Lv, Xinze ; Du, Haiwei ; Chen, Yu ; Hou, Ting

MYC-rearranged high-grade B-cell lymphoma (HGBCL) patients with concurrent BCL2 rearrangements (HGBCL-MYC/BCL2) often have a poor prognosis with standard chemoimmunotherapy and may benefit from more intensified regimens. Conventional fluorescence in situ hybridization (FISH) is the gold standard for detecting rearrangements, but it has several limitations. This study compared DNA- and RNA-sequencing with FISH to detect clinically relevant rearrangements in HGBCL. Archived formalin-fixed, paraffin-embedded samples from 34 patients who underwent FISH testing were analyzed using targeted DNA- and RNA-sequencing. DNA- and RNA-sequencing identified six and five out of the 12 MYC rearrangements detected by FISH, 10 and 6 out of 10 FISH-detectable BCL2 rearrangements, and 13 and 10 out of the 18 FISH-detectable BCL6 rearrangements. When combining DNA- and RNA-sequencing (integrated NGS), the sensitivity for detecting MYC, BCL2, and BCL6 rearrangements was 58.3%, 100%, and 73.7%, respectively. Both DNA- and RNA-sequencing detected the EIF4A2::BCL6 fusion missed by FISH. FISH identified 12 HGBCL-MYC/BCL2 out of 34 cases, while the integrated NGS strategy identified 7 cases, with 5 cases showing discordant results (41.7%). Additionally, patients with DLBCL/HGBCL-MYC/BCL2 had significantly shorter overall survival than other patients. 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.

01 Dec 2023·Pathology

TdT-positive high-grade B-cell lymphoma with BCOR and IDH1 mutations

Letter

Author: Yu, Yu-Ting ; Chen, Yi-Lin ; Chang, Kung-Chao ; Medeiros, L Jeffrey ; Lin, Kuan-Yu ; Chen, Ya-Ping

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