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BIOMARKER:

BCL6 translocation

i
Other names: BCL6, BCL5, BCL6A, LAZ3, ZBTB27, ZNF51, B-cell CLL/lymphoma 6
Entrez ID:
7d
A Study to Evaluate Adverse Events and Change in Disease Activity of Subcutaneous (SC) Epcoritamab As Monotherapy or Combined With Standard of Care Therapies in Adult Participants in China With B-Cell Non-Hodgkin Lymphoma (clinicaltrials.gov)
P1, N=49, Active, not recruiting, AbbVie | Phase classification: P1b/2 --> P1 | Trial completion date: Jan 2024 --> Dec 2024 | Trial primary completion date: Jan 2024 --> Dec 2024
Phase classification • Trial completion date • Trial primary completion date • Adverse events
|
BCL2 (B-cell CLL/lymphoma 2) • BCL6 (B-cell CLL/lymphoma 6)
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BCL6 translocation
|
Rituxan (rituximab) • lenalidomide • doxorubicin hydrochloride • cyclophosphamide • vincristine • Epkinly (epcoritamab-bysp)
16d
BELLWAVE-001: A Study of Nemtabrutinib (MK-1026) in Participants With Relapsed or Refractory Hematologic Malignancies (ARQ 531-101/MK-1026-001) (clinicaltrials.gov)
P1/2, N=190, Active, not recruiting, ArQule, Inc., a subsidiary of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc. (Rahway, NJ USA) | Trial completion date: Sep 2024 --> Sep 2025 | Trial primary completion date: Sep 2024 --> Sep 2025
Trial completion date • Trial primary completion date
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BCL2 (B-cell CLL/lymphoma 2) • BCL6 (B-cell CLL/lymphoma 6)
|
BTK mutation • BCL6 translocation • BTK C481
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nemtabrutinib (MK-1026)
2ms
Delineating the mechanism of fragility at BCL6 breakpoint region associated with translocations in diffuse large B cell lymphoma. (PubMed, Cell Mol Life Sci)
Further, we report the formation of intramolecular parallel G4 and triplex DNA, at Cluster II. Taken together, our studies reveal that multiple non-canonical DNA structures exist at the BCL6 cluster II breakpoint region and contribute to the fragility leading to BCL6 translocation in DLBCL patients.
Journal
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BCL6 (B-cell CLL/lymphoma 6)
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BCL6 translocation
3ms
Do MYC rearrangements Matter in HIV-Associated Large B Cell Lymphomas? "EUROMYC" Study (a European retrospective study). (PubMed, Blood Adv)
Among MYC+ patients, those who received intensive chemotherapy achieved a better outcome compared to patients who received non intensive treatment (complete remission 84% vs 52%, p 0,028; 5-year PFS 66% vs 36%, p 0,021). Our retrospective results suggest that HIV-associated LBCL with MYC rearrangement could be considered for an intensive therapeutic approach whenever possible, while (R)CHOP seems to give inferior results in this subset of patients in terms of complete remission and PFS.
Retrospective data • Journal
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BCL2 (B-cell CLL/lymphoma 2) • BCL6 (B-cell CLL/lymphoma 6)
|
MYC rearrangement • BCL6 translocation
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Rituxan (rituximab)
3ms
Non-IG::MYC in diffuse large B-cell lymphoma confers variable genomic configurations and MYC transactivation potential. (PubMed, Leukemia)
Translocation breakpoint analyses of 8 cases by TLC-based NGS showed no obvious genomic configuration that enables MYC transactivation in 3 of the 4 cases with non-IG::MYC, while a typical promoter substitution or IGH super enhancer juxtaposition in the remaining cases. The findings potentially explain variable MYC expression in DLBCL with MYC translocation, and also bear practical implications in its routine assessment.
Journal • IO biomarker
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MYC (V-myc avian myelocytomatosis viral oncogene homolog) • BCL2 (B-cell CLL/lymphoma 2) • BCL6 (B-cell CLL/lymphoma 6)
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MYC expression • MYC translocation • BCL6 translocation • BCL6 fusion
3ms
realMIND: Observational Study on Safety and Effectiveness of Tafasitamab in Combination With Lenalidomide in Patients With Relapsed or Refractory DLBCL (clinicaltrials.gov)
P=N/A, N=100, Recruiting, MorphoSys AG | N=1000 --> 100 | Trial completion date: Jul 2029 --> Aug 2026 | Trial primary completion date: Jul 2028 --> Oct 2025
Enrollment change • Trial completion date • Trial primary completion date • Combination therapy
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BCL2 (B-cell CLL/lymphoma 2) • BCL6 (B-cell CLL/lymphoma 6)
|
BCL6 translocation • BCL2 translocation
|
lenalidomide • Monjuvi (tafasitamab-cxix)
4ms
High Prevalence of MYD88 and CD79B Mutations and PD-L1 Alterations in Bone Marrow Large B Cell Lymphoma Associated with Hemophagocytic Lymphohistiocytosis (ASH 2023)
To the best of our knowledge, this is the first study exploring the molecular genetics of bone marrow large B cell lymphoma with HLH. Our study suggesting bone marrow large B cell lymphoma with HLH showed frequent MYD88/CD79B and PD-L1 alterations. Our study provided clues for the pathogenesis of bone marrow large B cell lymphoma with HLH and identified potential druggable targets for future clinical trials.
PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1) • MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • BCL6 (B-cell CLL/lymphoma 6) • IGH (Immunoglobulin Heavy Locus) • TET2 (Tet Methylcytosine Dioxygenase 2) • IKZF1 (IKAROS Family Zinc Finger 1) • CD79B (CD79b Molecule) • CD5 (CD5 Molecule) • PIM1 (Pim-1 Proto-Oncogene) • IRF4 (Interferon regulatory factor 4)
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CD79B mutation • PD-L1 amplification • CD79B mutation • BCL6 translocation
4ms
Primary bone diffuse large B-cell lymphoma (PB-DLBCL): a distinct extranodal lymphoma of germinal centre origin, with a common EZB-like mutational profile and good prognosis. (PubMed, Histopathology)
This study comprehensively characterizes PB-DLBCL as a separate entity with distinct clinical and morpho-molecular features. These insights may aid in developing tailored therapeutic strategies and shed light on its pathogenesis.
Journal • IO biomarker
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TP53 (Tumor protein P53) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • BCL2 (B-cell CLL/lymphoma 2) • BCL6 (B-cell CLL/lymphoma 6) • B2M (Beta-2-microglobulin)
|
TP53 mutation • B2M mutation • BCL2 rearrangement • BCL6 translocation
5ms
Clinical and Molecular Features of Patients with Double/Triple Hit Large B-Cell Lymphoma (ASH 2023)
On the other hand, HGBL-DH/TH displays aggressive features, including a high incidence of advanced disease at diagnosis, and inferior efficacy to standard-induced chemical immunotherapy with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). DHL-BCL2/THL exhibits similar clinical characteristics, prognostic outcomes, and molecular features that set it apart from DHL-BCL6. This implies the need for testing novel agents or therapeutic strategies to expedite treatment development for patients with DHL-BCL2/THL.
Clinical • IO biomarker
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BCL2 (B-cell CLL/lymphoma 2) • BCL6 (B-cell CLL/lymphoma 6) • CREBBP (CREB binding protein) • CD70 (CD70 Molecule) • BTG2 (BTG Anti-Proliferation Factor 2)
|
BCL6 rearrangement • MYC translocation • BCL2 rearrangement • MYC translocation + BCL2 translocation • BCL6 translocation • MYC translocation + BCL6 translocation • BCL2 translocation
|
Rituxan (rituximab) • doxorubicin hydrochloride • cyclophosphamide • vincristine
5ms
Deciphering the Clinical Benefit of Pola-R-CHP versus R-CHOP in Different Genetic Subtypes Beyond Cell of Origin in the POLARIX Study (ASH 2023)
Introduction: In the POLARIX study, polatuzumab vedotin in combination with rituximab plus cyclophosphamide, doxorubicin, and prednisone (Pola-R-CHP) demonstrated prolonged progression-free survival (PFS) vs rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in patients (pts) with previously untreated diffuse large B-cell lymphoma (DLBCL; NCT03274492; Tilly et al. In this exploratory biomarker analysis, we recapitulated that pts with molecularly defined DLBCL subtypes, including EZB and MCD by LymphGen and DZsig+ by RNAseq, have poor outcomes with R-CHOP therapy. In pts with the EZB and MCD subtypes, Pola-R-CHP appeared to improve 2-year PFS compared with R-CHOP. Pts with GCB DLBCL who were DZsig+ significantly benefited from Pola-R-CHP vs R-CHOP.
Clinical • IO biomarker
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MYC (V-myc avian myelocytomatosis viral oncogene homolog) • BCL2 (B-cell CLL/lymphoma 2) • MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • BCL6 (B-cell CLL/lymphoma 6) • CD79B (CD79b Molecule) • NOTCH2 (Notch 2)
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EZH2 mutation • CD79B mutation • CD79B mutation • MYC translocation • NOTCH2 mutation • BCL6 translocation • BCL6 fusion + NOTCH2 mutation • BCL2 translocation • BCL6 fusion
|
Rituxan (rituximab) • doxorubicin hydrochloride • cyclophosphamide • vincristine • Polivy (polatuzumab vedotin-piiq)
5ms
Clinical Characteristics and Outcomes of Limited Stage High Grade B-Cell Lymphoma with MYC/BCL2 and/or BCL6 Rearrangements: A Single Center Experience (ASH 2023)
Introduction: High grade B-cell lymphoma with MYC, BCL2 and/or BCL6 rearrangements (HGBCL MYC/BCL2 and/or BCL6-R) is a group of aggressive lymphomas associated with poor outcomes when treated with R-CHOP... In our series, pts with limited stage MYC/BCL2-R had poor outcomes while MYC/BCL6-R experienced favorable outcomes. There was no additional prognostic impact when BCL6-R is present with MYC/BCL2-R. This adds to the growing evidence that MYC/BCL6-R is not a poor prognostic factor in HGBCL.
Clinical
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MYC (V-myc avian myelocytomatosis viral oncogene homolog) • BCL2 (B-cell CLL/lymphoma 2) • BCL6 (B-cell CLL/lymphoma 6)
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LDH elevation • BCL6 rearrangement • BCL2 rearrangement • BCL6 translocation
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Rituxan (rituximab)
5ms
Plasma Circulating Tumor DNA (ctDNA) as an Alternative to Tissue DNA for Genotyping of DLBCL: Results from the POLARIX Study (ASH 2023)
Introduction: In the POLARIX study (NCT03274492), polatuzumab vedotin in combination with rituximab plus cyclophosphamide, doxorubicin, and prednisone (Pola-R-CHP) demonstrated prolonged progression-free survival (PFS) versus rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in patients with previously untreated diffuse large B-cell lymphoma (DLBCL; Tilly et al. Our analyses demonstrated that the mutation landscape of ctDNA in DLBCL characterized by the AVENIO ctDNA NHL assay resembles that of tumor tissue determined by WES. Patients with molecular subtypes defined by WES or ctDNA had similar PFS outcomes. Overall, these findings support the use of plasma ctDNA as an alternative to tumor tissue for the genotyping of DLBCL.
IO biomarker • Circulating tumor DNA
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TP53 (Tumor protein P53) • BCL2 (B-cell CLL/lymphoma 2) • NOTCH1 (Notch 1) • BCL6 (B-cell CLL/lymphoma 6) • TET2 (Tet Methylcytosine Dioxygenase 2) • KMT2D (Lysine Methyltransferase 2D) • CD79B (CD79b Molecule) • NOTCH2 (Notch 2) • TNFAIP3 (TNF Alpha Induced Protein 3) • DCHS1 (Dachsous Cadherin-Related 1) • TP53BP1 (Tumor Protein P53 Binding Protein 1)
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TP53 mutation • NOTCH1 mutation • TET2 mutation • KMT2D mutation • EZH2 mutation • MYD88 L265P • CD79B mutation • BCL6 rearrangement • CD79B mutation • NOTCH2 mutation • BCL2 rearrangement • BCL6 translocation • MYD88 L265P + CD79B mutation • TP53BP1 mutation • BCL2 translocation
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Rituxan (rituximab) • doxorubicin hydrochloride • cyclophosphamide • vincristine • Polivy (polatuzumab vedotin-piiq)
5ms
Enrollment closed • Adverse events
|
BCL2 (B-cell CLL/lymphoma 2) • BCL6 (B-cell CLL/lymphoma 6)
|
BCL6 translocation
|
Rituxan (rituximab) • lenalidomide • doxorubicin hydrochloride • cyclophosphamide • vincristine • Epkinly (epcoritamab-bysp)
5ms
Prognostic impact of miR-125b and miR-155b and their relationship with MYC and TP53 in diffuse large B-cell lymphoma: cell-of-origin classification matters. (PubMed, J Clin Exp Hematop)
This study demonstrated different pathways based on cell-of-origin classification and highlighted different clinical outcomes. miR-125b, miR-155b and TP53 expression may also represent potential prognostic factors in nGC-DLBCL.
Journal • IO biomarker
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TP53 (Tumor protein P53) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • BCL2 (B-cell CLL/lymphoma 2) • BCL6 (B-cell CLL/lymphoma 6)
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BCL2 expression • MYC expression • TP53 expression • miR-155 expression • BCL6 translocation
6ms
Clinicopathological analysis of diffuse large B-cell lymphoma using molecular biomarkers: a retrospective analysis from 7 Hungarian centers. (PubMed, Front Oncol)
The main objective of this study was to assess the application of the immunohistochemistry- and interphase fluorescence in situ hybridization (FISH)-based molecular markers in the diagnosis of DLBCL and its prognostic value in patients treated with rituximab-based immunochemotherapy...We did not find any difference in survival by GCB vs. non-GCB subtypes. These findings may improve prognostication in DLBCL and can contribute to designing further research in the area.
Retrospective data • Journal • IO biomarker
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MYC (V-myc avian myelocytomatosis viral oncogene homolog) • BCL2 (B-cell CLL/lymphoma 2) • BCL6 (B-cell CLL/lymphoma 6) • IRF4 (Interferon regulatory factor 4)
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MYC translocation • MYC positive • BCL6 translocation • IRF4 expression • BCL2 translocation
|
Rituxan (rituximab)
7ms
Genomic profiling of primary diffuse large B-cell lymphoma of the central nervous system suggests novel potential therapeutic targets. (PubMed, Mod Pathol)
Primary diffuse large B-cell lymphoma of the CNS (CNS-DLBCL) is an aggressive disease, with dismal prognosis despite the use of high dose methotrexate (MTX)-based polychemotherapy...MYD88 and CD79B predicted a longer survival in patients affected by CNS-DLBCL. Notably, we identified novel mutations that enrich the mutational landscape of CNS-DLBCL, suggest a role of PTEN-PI3K-AKT and RTK-RAS-MAPK signaling in a subset of CNS-DLBCL, and provide new potential therapeutic targets.
Journal • IO biomarker
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EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • PTEN (Phosphatase and tensin homolog) • BCL2 (B-cell CLL/lymphoma 2) • NOTCH1 (Notch 1) • MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • BCL6 (B-cell CLL/lymphoma 6) • CD79B (CD79b Molecule) • GNAS (GNAS Complex Locus) • PIM1 (Pim-1 Proto-Oncogene) • CASP8 (Caspase 8) • IRF4 (Interferon regulatory factor 4) • MME (Membrane Metalloendopeptidase)
|
TP53 mutation • KRAS mutation • PTEN mutation • MYD88 mutation • BCL2 expression • MYC rearrangement • CD79B mutation • BCL6 translocation
|
methotrexate
8ms
EPCORE DLBCL-1: A Phase 3 Trial of Epcoritamab vs Investigator's Choice Chemotherapy in R/R DLBCL (clinicaltrials.gov)
P3, N=552, Active, not recruiting, Genmab | Trial primary completion date: Apr 2028 --> Dec 2024
Trial primary completion date
|
BCL2 (B-cell CLL/lymphoma 2) • BCL6 (B-cell CLL/lymphoma 6)
|
CD20 positive • BCL6 translocation
|
Epkinly (epcoritamab-bysp)
8ms
Enrollment change • Adverse events
|
BCL2 (B-cell CLL/lymphoma 2) • BCL6 (B-cell CLL/lymphoma 6)
|
BCL6 translocation
|
Epkinly (epcoritamab-bysp)
9ms
Targeting MYC-driven lymphoma: lessons learned and future directions. (PubMed, Cancer Drug Resist)
Even though no MYC inhibitor has received regulatory approval to date, substantial efforts have been made to investigate avenues to render MYC a druggable target. Here, we summarize the different classes of molecules currently under development, which mostly target MYC indirectly in aggressive B-cell lymphomas, paying special attention to subtypes with MYC/BCL2 or BCL6 translocations or overexpression.
Review • Journal • IO biomarker
|
MYC (V-myc avian myelocytomatosis viral oncogene homolog) • BCL2 (B-cell CLL/lymphoma 2) • BCL6 (B-cell CLL/lymphoma 6)
|
MYC overexpression • MYC expression • BCL6 translocation
9ms
Trial completion date • Trial primary completion date • Adverse events
|
BCL2 (B-cell CLL/lymphoma 2) • BCL6 (B-cell CLL/lymphoma 6)
|
BCL6 translocation
|
Epkinly (epcoritamab-bysp)
9ms
EPCORE DLBCL-1: A Phase 3 Trial of Epcoritamab vs Investigator's Choice Chemotherapy in R/R DLBCL (clinicaltrials.gov)
P3, N=552, Active, not recruiting, Genmab | Recruiting --> Active, not recruiting | Trial completion date: Jun 2024 --> Apr 2028 | Trial primary completion date: Jun 2024 --> Apr 2028
Enrollment closed • Trial completion date • Trial primary completion date
|
BCL2 (B-cell CLL/lymphoma 2) • BCL6 (B-cell CLL/lymphoma 6)
|
CD20 positive • BCL6 translocation
|
Epkinly (epcoritamab-bysp)
10ms
Large B-cell lymphomas of immune privileged sites relapse via parallel clonal evolution from a common progenitor B-cell. (PubMed, Cancer Res)
Genetic alterations in genes involved in immune escape (HLA, CD274/PDL1LG2) were predominantly unique in primary and relapse samples and thus considered late genetic events. Together, this study indicates that primary and relapsed LBCL-IP follow an early parallel evolutionary pattern where the CPC contains genetic alterations that support prolonged survival/proliferation and retention in a memory B-cell state, followed by germinal center re-entry, aSHM and immune escape.
Journal
|
PD-L1 (Programmed death ligand 1) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • BCL6 (B-cell CLL/lymphoma 6) • CD79B (CD79b Molecule) • PD-L2 (Programmed Cell Death 1 Ligand 2) • TBL1XR1 (TBL1X Receptor 1)
|
CDKN2A mutation • CD79B mutation • CD79B mutation • BCL6 translocation
11ms
TRIAL IN PROGRESS: PHASE 1 TRIAL EVALUATING THE SAFETY AND TOLERABILITY OF ODRONEXTAMAB IN COMBINATION WITH CEMIPLIMAB IN RELAPSED/REFRACTORY AGGRESSIVE B-CELL NON-HODGKIN LYMPHOMA (EHA 2023)
This Ph 1 trial is determining the tolerability and preliminary clinical efficacy of odronextamab plus cemiplimab to treat pts with R/R aggressive B-NHL.
Clinical • P1 data • Combination therapy
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BCL2 (B-cell CLL/lymphoma 2) • BCL6 (B-cell CLL/lymphoma 6)
|
BCL6 translocation
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Libtayo (cemiplimab-rwlc) • odronextamab (REGN1979)
11ms
EPCORE DLBCL-1: A Phase 3 Trial of Epcoritamab vs Investigator's Choice Chemotherapy in R/R DLBCL (clinicaltrials.gov)
P3, N=552, Recruiting, Genmab | Trial primary completion date: Jun 2023 --> Jun 2024
Trial primary completion date
|
BCL2 (B-cell CLL/lymphoma 2) • BCL6 (B-cell CLL/lymphoma 6)
|
CD20 positive • BCL6 translocation
|
Epkinly (epcoritamab-bysp)
1year
A validated composite comorbidity index predicts outcomes of CAR T-cell therapy in patients with diffuse large B cell lymphoma. (PubMed, Blood Adv)
Severe4 was also a significant predictor of grade ≥3 cytokine release syndrome in the LC (odds ratio [OR]=2.43, p=0.042), while maintaining this trend in the VC (OR=2.05, p=0.114). Thus, our results indicate that adverse outcomes for patients with DLBCL meant to receive CART can be predicted using a simplified CIRS-derived comorbidity index.
Journal • CAR T-Cell Therapy
|
BCL6 (B-cell CLL/lymphoma 6)
|
BCL6 translocation
1year
Trial primary completion date • Adverse events
|
BCL2 (B-cell CLL/lymphoma 2) • BCL6 (B-cell CLL/lymphoma 6)
|
BCL6 translocation
|
Epkinly (epcoritamab-bysp)
over1year
A Phase 3 Study of Tafasitamab Plus Lenalidomide in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (firmMIND) (ASH 2022)
Treatment with the anti-CD20 monoclonal antibody (mAb) rituximab combined with cyclophosphamide, doxorubicin, vincristine, and prednisone is the standard first-line therapy; however, 30-40% of patients experience relapsed or refractory (R/R) disease (Harris LJ, et al. Secondary endpoints include safety, IRC-assessed progression-free survival, and overall survival. It is planned to enroll 81 patients into the study.
Clinical • P3 data
|
BCL2 (B-cell CLL/lymphoma 2) • CD19 (CD19 Molecule) • BCL6 (B-cell CLL/lymphoma 6)
|
CD19 expression • BCL6 translocation
|
Rituxan (rituximab) • lenalidomide • doxorubicin hydrochloride • cyclophosphamide • vincristine • Monjuvi (tafasitamab-cxix)
over1year
When malignancy hits twice - synchronous gastric carcinoma and non-Hodgkin-B-cell lymphoma in a patient with common variable immunodeficiency. (PubMed, Z Gastroenterol)
While the first upper gastrointestinal endoscopy for routine surveillance purposes was uneventful, the second one after developing unexplained weight loss revealed two new neoplastic lesions in the stomach. The histological evaluation revealed a poorly differentiated adenocarcinoma infiltrating the muscularis propria forcing gastrectomy as well as a high-grade B-non-Hodgkin-lymphoma with detection of a MYC- and BCL6-translocation, necessitating chemotherapy with R-CHOP.This case emphasizes the necessity of high awareness for gastric neoplasia in patients with CVID and highlights the need of a standardized yet not established endoscopic surveillance protocol for this vulnerable group.
Journal
|
BCL6 (B-cell CLL/lymphoma 6)
|
BCL6 translocation
|
Rituxan (rituximab)
over1year
The Position of MYC Rearrangements in the Genomic Landscape of Diffuse Large B-Cell Lymphoma (ASH 2022)
Top: Classification of samples according to MYC status, Lymphgen assignment, and cell of origin (COO). Right: Genomic alterations (copy number alterations, CNAs; mutations and translocations) enriched in NMF clusters C1 to C5.
IO biomarker
|
MYC (V-myc avian myelocytomatosis viral oncogene homolog) • BCL2 (B-cell CLL/lymphoma 2) • BCL6 (B-cell CLL/lymphoma 6)
|
MYC rearrangement + BCL2 rearrangement • MYC rearrangement • BCL6 rearrangement • BCL2 rearrangement • BCL6 translocation
over1year
Relapse Timing Is Associated with Distinct Evolutionary Dynamics and Response to Salvage Therapy in DLBCL (ASH 2022)
Archival formalin-fixed paraffin-embedded biopsies with DLBCL morphology were selected from 146 R-CHOP treated patients, of which 35% had detectable low-grade lymphoma at some point in their disease course... These experiments suggest that LRs, when clonally related, usually arise via convergent evolution from a common precursor cell (CPC) population where the driver mutation profile at both diagnosis and relapse is constrained by the genetics of the CPC. The superior outcomes on salvage therapy and HSCT support the hypothesis that LRs generally represent new chemotherapy-naïve disease and have implications for optimal patient management in the era of CAR-T cell therapy.
IO biomarker
|
MYC (V-myc avian myelocytomatosis viral oncogene homolog) • BCL2 (B-cell CLL/lymphoma 2) • BCL6 (B-cell CLL/lymphoma 6) • CREBBP (CREB binding protein)
|
MYC translocation • BCL6 translocation • MYC translocation + BCL6 translocation • BCL2 translocation
|
Rituxan (rituximab)
over1year
Double-Hit B-Cell Lymphoma With Dim CD45 Expression and Absence of Surface Immunoglobulin Light Chains (CAP 2022)
DHL with immature features is associated with a poor clinical outcome. This patient died 10 months after diagnosis.
IO biomarker
|
KIT (KIT proto-oncogene, receptor tyrosine kinase) • BCL2 (B-cell CLL/lymphoma 2) • CD20 (Membrane Spanning 4-Domains A1) • CCND1 (Cyclin D1) • BCL6 (B-cell CLL/lymphoma 6) • CD38 (CD38 Molecule) • PAX5 (Paired Box 5) • CD34 (CD34 molecule) • PTPRC (Protein Tyrosine Phosphatase Receptor Type C) • CD79A (CD79a Molecule) • MME (Membrane Metalloendopeptidase) • SPN (Sialophorin)
|
MYC rearrangement • BCL2 rearrangement • PTPRC expression • BCL6 translocation
over1year
Double-Hit B-Cell Lymphoma With Dim CD45 Expression and Absence of Surface Immunoglobulin Light Chains (CAP 2022)
DHL with immature features is associated with a poor clinical outcome. This patient died 10 months after diagnosis.
IO biomarker
|
KIT (KIT proto-oncogene, receptor tyrosine kinase) • BCL2 (B-cell CLL/lymphoma 2) • CD20 (Membrane Spanning 4-Domains A1) • CCND1 (Cyclin D1) • BCL6 (B-cell CLL/lymphoma 6) • CD38 (CD38 Molecule) • PAX5 (Paired Box 5) • CD34 (CD34 molecule) • PTPRC (Protein Tyrosine Phosphatase Receptor Type C) • CD79A (CD79a Molecule) • MME (Membrane Metalloendopeptidase) • SPN (Sialophorin)
|
MYC rearrangement • BCL2 rearrangement • PTPRC expression • BCL6 translocation
over1year
BELLWAVE-001: A Study of Nemtabrutinib (MK-1026) (ARQ 531) in Participants With Selected Hematologic Malignancies (clinicaltrials.gov)
P1/2, N=190, Active, not recruiting, ArQule, Inc. (a wholly owned subsidiary of Merck Sharp and Dohme, a subsidiary of Merck & Co., Inc.) | Trial completion date: Sep 2023 --> Sep 2024 | Trial primary completion date: Sep 2023 --> Sep 2024
Trial completion date • Trial primary completion date
|
BCL2 (B-cell CLL/lymphoma 2) • BCL6 (B-cell CLL/lymphoma 6)
|
BTK mutation • BCL6 translocation • BTK C481
|
nemtabrutinib (MK-1026)
over1year
Enrollment open • Adverse events
|
BCL2 (B-cell CLL/lymphoma 2) • BCL6 (B-cell CLL/lymphoma 6)
|
BCL6 translocation
|
Epkinly (epcoritamab-bysp)
over1year
New P2 trial
|
BCL2 (B-cell CLL/lymphoma 2) • BCL6 (B-cell CLL/lymphoma 6)
|
BCL6 translocation
|
Epkinly (epcoritamab-bysp)
over1year
Trial completion date • Trial primary completion date • Combination therapy • Circulating tumor DNA
|
MYC (V-myc avian myelocytomatosis viral oncogene homolog) • BCL2 (B-cell CLL/lymphoma 2) • CD20 (Membrane Spanning 4-Domains A1) • BCL6 (B-cell CLL/lymphoma 6)
|
CD20 positive • MYC expression • BCL6 translocation
|
Rituxan (rituximab) • doxorubicin hydrochloride • cyclophosphamide • vincristine • Actemra IV (tocilizumab) • Columvi (glofitamab-gxbm)
almost2years
OUTCOMES OF HIGH-RISK LARGE B-CELL LYMPHOMA TREATED WITH STANDARD OF CARE CHEMOIMMUNOTHERAPY: A NON-RANDOMIZED COMPARISON TO FRONTLINE CAR-T CELL THERAPY (EHA 2022)
Patients were treated with DA-EPOCH-R (n=11, 21%) and R-CHOP (n=41, 77%)...Conclusion In this nonrandomized study of high risk LBCL, the efficacy of axi-cel in the ZUMA-12 was numerically higher than SOC CIT. The PFS and OS in our cohort was lower despite majority of patients achieving early CR per iPET. This analysis supports a potential trial of frontline CAR-T versus SOC CIT for high risk LBCL.
Clinical • CAR T-Cell Therapy
|
BCL2 (B-cell CLL/lymphoma 2) • BCL6 (B-cell CLL/lymphoma 6)
|
BCL6 translocation
|
Rituxan (rituximab) • Yescarta (axicabtagene ciloleucel)
almost2years
Enrollment open
|
ALK (Anaplastic lymphoma kinase) • BCL2 (B-cell CLL/lymphoma 2) • BCL6 (B-cell CLL/lymphoma 6)
|
BCL6 translocation
|
Rituxan (rituximab) • doxorubicin hydrochloride • cyclophosphamide • etoposide IV • daunorubicin • Polivy (polatuzumab vedotin-piiq) • Neupogen (filgrastim)
almost2years
Polatuzumab Vedotin and Combination Chemotherapy for the Treatment of Untreated Aggressive Large B-cell Lymphoma (clinicaltrials.gov)
P1, N=50, Suspended, University of Washington | N=18 --> 50 | Trial completion date: Apr 2027 --> Dec 2031 | Trial primary completion date: Apr 2022 --> Dec 2026
Enrollment change • Trial completion date • Trial primary completion date
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ALK (Anaplastic lymphoma kinase) • BCL2 (B-cell CLL/lymphoma 2) • BCL6 (B-cell CLL/lymphoma 6)
|
BCL6 translocation
|
Rituxan (rituximab) • doxorubicin hydrochloride • cyclophosphamide • etoposide IV • daunorubicin • Polivy (polatuzumab vedotin-piiq) • Neupogen (filgrastim)
almost2years
First-in-human dose escalation study of cyclin-dependent kinase-9 inhibitor VIP152 in patients with advanced malignancies shows early signs of clinical efficacy. (PubMed, Clin Cancer Res)
VIP152 monotherapy, administered intravenously once weekly, demonstrated a favorable safety profile and evidence of clinical benefit in patients with advanced HGL and solid tumors.
Clinical • P1 data • Journal
|
BCL2 (B-cell CLL/lymphoma 2) • BCL6 (B-cell CLL/lymphoma 6) • CDK9 (Cyclin Dependent Kinase 9)
|
BCL6 translocation • BCL2 translocation
|
enitociclib (VIP152)
almost2years
Enrollment open • Adverse events
|
BCL2 (B-cell CLL/lymphoma 2) • BCL6 (B-cell CLL/lymphoma 6)
|
BCL6 rearrangement • BCL2 rearrangement • BCL6 translocation
|
Rituxan (rituximab) • lenalidomide • doxorubicin hydrochloride • cyclophosphamide • vincristine • Epkinly (epcoritamab-bysp)