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    BIOMARKER:

    MYD88 L265P

    i
    Other names: MYD88, MYD88 Innate Immune Signal Transduction Adaptor, Myeloid Differentiation Primary Response Protein MyD88, Myeloid Differentiation Primary Response Gene (88), Myeloid Differentiation Primary Response 88, Mutant Myeloid Differentiation Primary Response 88, MYD88D
    Entrez ID:
    4615
    Related biomarkers:
    Expression
    Mutation
    Others
    14d
    High Prevalence of MYD88 and CD79B Mutations in Primary Sinonasal Diffuse Large B-Cell Lymphoma: Identification of an MCD-like Subtype. (PubMed, Am J Surg Pathol)
    In conclusion, our study highlights a high prevalence of MYD88 and CD79B mutations in PSDLBCL, identifying an aggressive MCD-like subtype with a distinct relapse pattern. This molecular subclassification can be helpful for both prognostic prediction and therapeutic strategy in patients with PSDLBCL.
    Journal • IO biomarker
    |
    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)
    |
    MYD88 mutation • MYD88 L265P • CD79B mutation • CD79B mutation • BCL6 translocation • BCL2 translocation
    29d
    Impact of chromosomal aberrations detected by chromosome banding analysis in symptomatic Waldenström's macroglobulinemia. (PubMed, Ann Hematol)
    With a median follow-up of 73 months, the median TTNT in patients with and without CAs was 27 and 68 months, respectively. CAs with CBA may be associated with clinical aggressiveness and shorter TTNT in sWM.
    Journal
    |
    MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • CXCR4 (Chemokine (C-X-C motif) receptor 4)
    |
    MYD88 L265P • CXCR4 mutation
    1m
    Utility of clinical, laboratory, and lymph node MYD88 L265P mutation in risk assessment of diffuse large B-cell lymphoma patients. (PubMed, J Egypt Natl Canc Inst)
    Our findings indicate a high frequency of MYD88 L265P mutations in our study population and not associated with prognostic markers or the outcome of the disease.
    Journal
    |
    MYD88 (MYD88 Innate Immune Signal Transduction Adaptor)
    |
    MYD88 mutation • MYD88 L265P
    1m
    Testicular large B-cell lymphoma is genetically similar to PCNSL and distinct from nodal DLBCL. (PubMed, Hemasphere)
    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.
    Journal • IO biomarker
    |
    BCL2 (B-cell CLL/lymphoma 2) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • BCL6 (B-cell CLL/lymphoma 6) • ETV6 (ETS Variant Transcription Factor 6) • CD79B (CD79b Molecule) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • EP300 (E1A binding protein p300) • PIM1 (Pim-1 Proto-Oncogene) • NODAL (Nodal Growth Differentiation Factor) • TBL1XR1 (TBL1X Receptor 1)
    |
    CDKN2A deletion • MYD88 L265P • MYC rearrangement • BCL6 rearrangement • BCL2 rearrangement • ETV6 mutation
    1m
    Next-generation integrated sequencing identifies poor prognostic factors in patients with MYD88-mutated chronic lymphocytic leukemia in Taiwan. (PubMed, Pathobiology)
    IGLL5, MYD88, and KMT2D mutations were enriched in Taiwanese CLL, and co-occurrence of MYD88 mutations with KMT2D or/and IGLL5 mutations was associated with a poorer prognosis.
    Journal
    |
    MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • IGH (Immunoglobulin Heavy Locus) • KMT2D (Lysine Methyltransferase 2D) • IGLL5 (Immunoglobulin Lambda Like Polypeptide 5) • DSCAM (DS Cell Adhesion Molecule) • TCHH (Trichohyalin)
    |
    MYD88 mutation • KMT2D mutation • MYD88 L265P • IGLL5 mutation
    2ms
    Blood and cerebrospinal fluid biomarkers in neuro-oncology. (PubMed, Curr Opin Neurol)
    This review summarizes the current knowledge and future perspectives of liquid biopsy of blood and CSF for diagnosis and monitoring of primary CNS tumors.
    Journal
    |
    PTEN (Phosphatase and tensin homolog) • MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • TERT (Telomerase Reverse Transcriptase) • SMARCB1 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily B, Member 1) • SMO (Smoothened Frizzled Class Receptor) • KLF4 (Kruppel-like factor 4)
    |
    EGFR mutation • PTEN mutation • MYD88 L265P • NF2 mutation • TERT mutation • SMO mutation • TERT promoter mutation
    2ms
    Intraparenchymal low-grade B-cell lymphomas of the central nervous system: Clinicopathologic and molecular analysis of three cases and a review of the literature. (PubMed, Ann Diagn Pathol)
    Our findings expand knowledge on their clinical and molecular features. We present the first molecular profile of primary CNS intraparenchymal EMZL, underscoring the need for further research to understand their biology and optimize treatment strategies.
    Review • Journal
    |
    ARID1A (AT-rich interaction domain 1A) • MYD88 (MYD88 Innate Immune Signal Transduction Adaptor)
    |
    ARID1A mutation • MYD88 mutation • MYD88 L265P • SPEN mutation
    2ms
    Paraneoplastic myelitis associated with Waldenström macroglobulinemia responsive to treatment with ibrutinib - venetoclax: A case report. (PubMed, eNeurologicalSci)
    Based on radiographic findings, a diagnosis of paraneoplastic LETM was made and he was treated acutely with IV methylprednisolone followed by a quick oral prednisone taper. However, he subsequently relapsed and symptomatically worsened while on rituximab therapy...Our observation of sustained disease response in this patient may support a role for concurrent BTK and BCL2 inhibition in paraneoplastic myelitis associated with B-cell lymphoproliferative disorders. However, this observation needs to be validated in larger cohort studies and potentially in clinical trials if further data are supportive.
    Journal • IO biomarker
    |
    MYD88 (MYD88 Innate Immune Signal Transduction Adaptor)
    |
    MYD88 L265P
    |
    Venclexta (venetoclax) • Imbruvica (ibrutinib) • Rituxan (rituximab) • prednisone • methylprednisolone sodium succinate
    2ms
    Investigating the frequency of somatic MYD88 L265P mutation in primary ocular adnexal B cell lymphoma. (PubMed, Mol Biol Rep)
    The present study indicates that the MYD88 L265P mutation is relatively infrequent in our cohort, underscoring the need for further validation in additional cohorts.
    Journal
    |
    MYD88 (MYD88 Innate Immune Signal Transduction Adaptor)
    |
    MYD88 L265P
    2ms
    Diagnosis and Risk Stratification in Waldenström Macroglobulinemia. (PubMed, J Natl Compr Canc Netw)
    The discovery of the recurrent MYD88L265P gain-of-function point mutation and the subclonal CXCR4 mutations has helped improve our understanding of the WM biology, and the prognostic impact of these mutations is under evaluation, with somewhat inconsistent findings thus far across studies. This review discusses the clinical presentation, diagnostic criteria, and prognostic markers of WM.
    Review • Journal
    |
    CXCR4 (Chemokine (C-X-C motif) receptor 4)
    |
    MYD88 L265P • CXCR4 mutation
    6ms
    RITZ: Comparison Between Rituximab Plus Zanubrutinib Versus Rituximab Monotherapy in Untreated SMZL Patients (clinicaltrials.gov)
    P3, N=120, Recruiting, International Extranodal Lymphoma Study Group (IELSG) | Not yet recruiting --> Recruiting
    Enrollment open
    |
    MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • CCND1 (Cyclin D1) • BCL6 (B-cell CLL/lymphoma 6) • IL2RA (Interleukin 2 receptor, alpha) • MME (Membrane Metalloendopeptidase) • ITGAE (Integrin Subunit Alpha E) • ISG20 (Interferon Stimulated Exonuclease Gene 20)
    |
    MYD88 L265P • CCND1 expression • IL2RA expression
    |
    Rituxan (rituximab) • Brukinsa (zanubrutinib) • Truxima (rituximab-abbs)
    6ms
    A Study of ICP-022 in Patients With R/R DLBCL (clinicaltrials.gov)
    P2, N=3, Completed, Beijing InnoCare Pharma Tech Co., Ltd. | Recruiting --> Completed | N=85 --> 3
    Trial completion • Enrollment change
    |
    MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • CD79B (CD79b Molecule)
    |
    MYD88 L265P
    |
    Yinuokai (orelabrutinib)
    6ms
    The Molecular Landscape of Primary CNS Lymphomas (PCNSLs) in Children and Young Adults. (PubMed, Cancers (Basel))
    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.
    Journal • IO biomarker
    |
    BCL2 (B-cell CLL/lymphoma 2) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • CCND1 (Cyclin D1) • BCL6 (B-cell CLL/lymphoma 6) • CARD11 (Caspase Recruitment Domain Family Member 11) • IRF4 (Interferon regulatory factor 4)
    |
    CDKN2A deletion • MYD88 mutation • MYD88 L265P • CARD11 mutation • BCL2 rearrangement
    7ms
    Primary Large B-cell Lymphomas of Immune-Privileged Sites. (PubMed, Blood)
    In this review, we describe the overlapping clinical, pathologic, and molecular features of IP-LBCL and highlight important considerations for diagnosis, staging and treatment. We also discuss potential therapeutic vulnerabilities of IP-LBCL including sensitivity to inhibitors of Bruton's tyrosine kinase, immunomodulatory agents, and immunotherapy.
    Journal • IO biomarker
    |
    MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • CD79B (CD79b Molecule)
    |
    MYD88 mutation • MYD88 L265P
    7ms
    Mutation landscape in Chinese nodal diffuse large B-cell lymphoma by targeted next generation sequencing and their relationship with clinicopathological characteristics. (PubMed, BMC Med Genomics)
    This study presents the mutation landscape in Chinese nodal DLBCL, highlights the genetic heterogeneity of DLBCL and shows the role of panel-based NGS to prediction of prognosis and potential molecular targeted therapy in DLBCL. More precise genetic classification needs further investigations.
    Journal • Next-generation sequencing • IO biomarker
    |
    TP53 (Tumor protein P53) • BCL2 (B-cell CLL/lymphoma 2) • MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • KMT2D (Lysine Methyltransferase 2D) • CD79B (CD79b Molecule) • KMT2C (Lysine Methyltransferase 2C) • PIM1 (Pim-1 Proto-Oncogene) • SOCS1 (Suppressor Of Cytokine Signaling 1) • H1-4 (H1.4 Linker Histone, Cluster Member) • DDX3X (DEAD-Box Helicase 3 X-Linked)
    |
    TP53 mutation • MYD88 L265P
    7ms
    Detection of circulating tumor DNA in plasma of patients with primary CNS lymphoma by digital droplet PCR. (PubMed, BMC Cancer)
    The low detection rate of MYD88 L265P and CD79B Y196 mutations in cfDNA in the plasma of PCNSL patients argues against its use in routine diagnostics. However, detection of MYD88 L265P by ddPCR in cfDNA in the plasma could be considered in challenging cases.
    Journal • Circulating tumor DNA
    |
    MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • CD79B (CD79b Molecule)
    |
    MYD88 L265P • CD79B mutation
    8ms
    Bruton Tyrosine Kinase Inhibition: an Effective Strategy to Manage Waldenström Macroglobulinemia. (PubMed, Curr Hematol Malig Rep)
    The findings of the RAINBOW trial (NCT046152), comparing the dexamethasone, rituximab, and cyclophosphamide (DRC) regimen to the first-generation, ibrutinib are awaited, but more studies are needed to draw definitive conclusions on the comparative efficacy of chemoimmunotherapy and BTKi. Complete response is elusive with BTKi, and combination regimens to improve upon the efficacy and limit the treatment duration are also under evaluation in WM.
    Review • Journal • IO biomarker
    |
    MYD88 (MYD88 Innate Immune Signal Transduction Adaptor)
    |
    MYD88 mutation • MYD88 L265P • BTK C481 • MYD88 wild-type
    |
    Imbruvica (ibrutinib) • Rituxan (rituximab) • cyclophosphamide • dexamethasone
    8ms
    Mutational, immune microenvironment, and clinicopathological profiles of diffuse large B-cell lymphoma and follicular lymphoma with BCL6 rearrangement. (PubMed, Virchows Arch)
    In conclusion, both BCL6-R-positive FL and BCL6-R-positive DLBCL had a common mutational profile; but also, differences. DLBCL cases had a higher density of microenvironment markers.
    Journal • PD(L)-1 Biomarker • IO biomarker
    |
    PD-L1 (Programmed death ligand 1) • BCL2 (B-cell CLL/lymphoma 2) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • NOTCH1 (Notch 1) • MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • BCL6 (B-cell CLL/lymphoma 6) • KMT2D (Lysine Methyltransferase 2D) • NOTCH2 (Notch 2) • CREBBP (CREB binding protein) • CD163 (CD163 Molecule) • ARID1B (AT-Rich Interaction Domain 1B) • CD36 (thrombospondin receptor) • IL10 (Interleukin 10) • RHOA (Ras homolog family member A) • PIM1 (Pim-1 Proto-Oncogene) • CSF1R (Colony stimulating factor 1 receptor) • HLA-B (Major Histocompatibility Complex, Class I, B) • H1-4 (H1.4 Linker Histone, Cluster Member) • PLOD2 (procollagen-lysine,2-oxoglutarate 5-dioxygenase 2) • BTG2 (BTG Anti-Proliferation Factor 2) • LAIR1 (Leukocyte Associated Immunoglobulin Like Receptor 1)
    |
    ATM mutation • MYD88 L265P • BCL6 rearrangement • ARID1B mutation • IL10-L • PIM1 mutation • MYC negative
    8ms
    A Rare Case of Non-IgM Lymphoplasmacytic Lymphoma with Unusual Lack of Immunoglobulin Light Chain Production. (PubMed, Am J Case Rep)
    The patient received 6 cycles of rituximab and bendamustine treatment, and no residual marrow involvement was found on the follow-up bone marrow biopsy. CONCLUSIONS We report a non-IgM LPL case featuring no light chain production and no heavy chain secretion, which we believe is the first reported case of this kind in the literature.
    Journal
    |
    MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • CXCR4 (Chemokine (C-X-C motif) receptor 4) • IGK (Immunoglobulin Kappa Locus)
    |
    MYD88 L265P • CXCR4 mutation
    |
    Rituxan (rituximab) • bendamustine
    8ms
    The dual HCK/BTK inhibitor KIN-8194 impairs growth and integrin-mediated adhesion of BTKi-resistant mantle cell lymphoma. (PubMed, Leukemia)
    Here, we show that KIN-8194, a dual inhibitor of BTK and HCK with in vivo activity against Myd88-L265P-driven diffuse large B-cell lymphoma and Waldenström Macroglobulinemia, has a potent growth inhibitory effect in MCL cell lines and primary MCL cells, irrespective of their sensitivity to BTKi (ibrutinib and acalabrutinib). Taken together, our data demonstrate that KIN-8194 inhibits growth and integrin-mediated adhesion of BTKi-sensitive MCL cells, as well as MCL cells with primary or acquired BTKi resistance. This renders KIN-8194 a promising novel treatment for MCL patients.
    Journal
    |
    MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • HCK (HCK Proto-Oncogene)
    |
    MYD88 L265P
    |
    Imbruvica (ibrutinib) • Calquence (acalabrutinib) • KIN-8194
    9ms
    Single-cell analysis of MYD88L265P and MYD88WT Waldenström macroglobulinemia patients. (PubMed, Hemasphere)
    Finally, gene expression analysis showed common transcriptional features between patients compared to the healthy control but also differentially expressed genes between MYD88 L265P and MYD88 WT patients involved in distinct pathways, including NFκΒ, BCL2, and BTK. Overall, our data highlight the intra-tumor clonal heterogeneity in WM with potential prognostic and therapeutic implications.
    Journal • IO biomarker
    |
    BCL2 (B-cell CLL/lymphoma 2) • MYD88 (MYD88 Innate Immune Signal Transduction Adaptor)
    |
    MYD88 L265P • MYD88 wild-type
    9ms
    Nomogram for predicting survival of patients with diffuse large B-cell lymphoma. (PubMed, Ann Hematol)
    The present nomograms incorporating IPI factors and the MYD88/CD79B mutation have sufficient discrimination ability, and may effectively predict prognosis in DLBCL patients. The prognostic models we have presented here may help clinicians personalize prognostic assessments and clinical decisions.
    Journal
    |
    MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • CD79B (CD79b Molecule)
    |
    MYD88 L265P • CD79B mutation • CD79B mutation
    9ms
    PlentiPlex™ MYD88 Waldenström lymphoma qPCR assay: A highly sensitive method for detection of MYD88 L265P mutation. (PubMed, Int J Lab Hematol)
    Our data demonstrate that PlentiPlex™ MYD88 Waldenström lymphoma qPCR assay is a fast, highly sensitive, and specific method for the detection of MYD88 L265P compared with conventional AS-PCR.
    Journal
    |
    MYD88 (MYD88 Innate Immune Signal Transduction Adaptor)
    |
    MYD88 L265P
    9ms
    Mutational landscape in Waldenström macroglobulinemia evaluated using a next-generation sequencing lymphoma panel in routine clinical practice. (PubMed, Leuk Lymphoma)
    NGS performance for the MYD88L265P variant was 96% when compared to qPCR. In conclusion, targeted NGS provided important diagnostic and prognostic information in a routine clinical setting.
    Journal • Next-generation sequencing
    |
    TP53 (Tumor protein P53) • ARID1A (AT-rich interaction domain 1A) • MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • CXCR4 (Chemokine (C-X-C motif) receptor 4) • CD79B (CD79b Molecule) • BIRC3 (Baculoviral IAP repeat containing 3)
    |
    TP53 mutation • ARID1A mutation • MYD88 L265P
    10ms
    "Quadruple-hit" primary testicular diffuse large B-cell lymphoma with MYD88 L265P mutation, IGH::MYC, and IRF4- and BCL6-rearrangements. (PubMed, J Hematop)
    Gene expression profiling demonstrated an activated B-cell expression profile. This case highlights the genetic complexity of DLBCL arising in the testis and questions the clinical significance of the identified genetic abnormalities.
    Journal
    |
    MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • BCL6 (B-cell CLL/lymphoma 6) • IRF4 (Interferon regulatory factor 4)
    |
    MYD88 mutation • MYD88 L265P • BCL6 rearrangement
    11ms
    Diagnostic methods for primary vitreoretinal lymphoma: A systematic review. (PubMed, Surv Ophthalmol)
    Overall, our systematic review found that an IL-10/IL-6 ratio greater or equal to one may provide the highest sensitivity in identifying patients with PVRL. Future studies are needed to employ multiple diagnostic tools to aid in the detection of PVRL to further establish nuanced guidelines when determining the optimal diagnostic tool to use in diverse patient populations.
    Review • Journal
    |
    MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • IGH (Immunoglobulin Heavy Locus) • CD79B (CD79b Molecule) • IL10 (Interleukin 10) • IL6R (Interleukin 6 receptor)
    |
    MYD88 L265P • CD79B mutation • CD79B mutation • MYD88 L265P + CD79B mutation
    12ms
    CXCR4 S338X Promotes Resistance to Second Generation BTK Inhibitor and BCL-2 Inhibitor in WM Cells (ASH 2023)
    The aim of this study was to further investigate the effect of CXCR4 S338X on BTK inhibitors (ibrutinib and zanubrutinib) and a BCL-2 inhibitor (venetoclax) resistance. The above data demonstrate the role of CXCR4 S338X mutation in drug resistance and suggest the necessity to develop therapeutic strategies to address this issue and overcome this therapeutic barrier in WM. Data on more cell lines and downstream signaling will be presented at the meeting.
    IO biomarker
    |
    MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • CXCR4 (Chemokine (C-X-C motif) receptor 4) • CASP8 (Caspase 8) • CASP9 (Caspase 9) • ANXA5 (Annexin A5)
    |
    MYD88 L265P • CXCR4 mutation • CXCR4 S338X • CXCR4 expression
    |
    Venclexta (venetoclax) • Imbruvica (ibrutinib) • Brukinsa (zanubrutinib)
    12ms
    The Efficacy and Safety of Zanubrutinib, Dexamethasone and or Not Cyclophosphamide Regimen in Symptomatic Waldenstrom Macroglobulinnemia (ASH 2023)
    After 8 cycles, patients with VGPR remission receive Chlorambucil 6mg D1-4,15-18, dexamethasone 20mg D1-4,15-18, cyclophosphamide 300mg, D1-4,15-18 for 4cycles, others receive Zanubrutinib as maintenance. These results demonstrate that zanubrutinib, dexamethasone and or not cyclophosphamide are quickly effective in the treatment of WM, with more deeper response and less toxicity, maybe treatment discontinued by combining with cyclophosphamide after deep remission. Comments*The regimen of ZD: Zanubrutinib 240mg d1-28, dexamethasone 20mg D1-4,15-18. Patients more than 75 years old, Zanubrutinib 160mg d1-28, dexamethasone 10mg D1-4,15-18.
    Clinical
    |
    CXCR4 (Chemokine (C-X-C motif) receptor 4)
    |
    MYD88 L265P • CXCR4 mutation
    |
    Rituxan (rituximab) • cyclophosphamide • Brukinsa (zanubrutinib) • Leukeran (chlorambucil) • fludarabine IV • Mustargen (mechlorethamine)
    12ms
    The Incidence, Clinical Application and Prognostic Significance of MYD88 and CXCR4 Mutation in Chinese Patients with Lymphoplasmacytic Lymphoma/ Waldenström Macroglobulinemia (ASH 2023)
    NGS was the most sensitive method for detecting CXCR4 mutation. MYD88 mutation had prognostic significance in BTKi-based therapy, while CXCR4 mutation indicated higher tumor burden and inferior survival in BTKi-based therapy.
    Clinical
    |
    MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • CXCR4 (Chemokine (C-X-C motif) receptor 4)
    |
    MYD88 mutation • MYD88 L265P • CXCR4 mutation • MYD88 mutation + CXCR4 mutation • MYD88 L265P + CXCR4 mutation • MYD88 wild-type
    12ms
    RCHOP Plus High-Dose Methotrexate As First-Line Therapy in Large B-Cell Lymphoma with Testis Involvement (ASH 2023)
    PTL may benefit from HD-MTX in preventing relapse, while alternative treatments should be explored for DLBCL-T. Future studies should consider PTL and DLBCL-T as separate entities to better understand their characteristics and optimize treatment strategies.
    Clinical • PD(L)-1 Biomarker • IO biomarker
    |
    PD-L1 (Programmed death ligand 1) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • BCL2 (B-cell CLL/lymphoma 2) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • PD-1 (Programmed cell death 1) • BCL6 (B-cell CLL/lymphoma 6) • CD79B (CD79b Molecule) • B2M (Beta-2-microglobulin) • CREBBP (CREB binding protein) • CARD11 (Caspase Recruitment Domain Family Member 11) • EP300 (E1A binding protein p300) • TCF3 (Transcription Factor 3) • PIM1 (Pim-1 Proto-Oncogene) • IRF4 (Interferon regulatory factor 4) • CD58 (CD58 Molecule) • PRDM1 (PR/SET Domain 1) • NFKBIE (NFKB Inhibitor Epsilon)
    |
    PD-L1 expression • MYD88 mutation • MYD88 L265P • PD-1 expression • BCL2 expression • MYC expression • CD79B mutation • PIM1 mutation
    |
    Rituxan (rituximab) • methotrexate IV
    12ms
    A Phase 4, Observational Study Evaluating the Efficacy and Safety of the Bruton Tyrosine Kinase Inhibitor (BTKi) Zanubrutinib in Patients with Waldenström Macroglobulinemia (WM) (ASH 2023)
    Background and Significance: Zanubrutinib, a next-generation, selective BTKi, is approved for treatment of WM based on data from the phase 3 ASPEN study (NCT03053440), in which zanubrutinib showed a favorable benefit-risk profile vs ibrutinib, a first-generation BTKi, in patients with symptomatic WM (Tam CS, et al. MRR, VGPR+ rate, and ORR will be presented with 95% CIs, and median DOR will be estimated with the Kaplan-Meier method. The study is currently open for enrollment.
    Clinical • Observational data • P4 data
    |
    MYD88 (MYD88 Innate Immune Signal Transduction Adaptor)
    |
    MYD88 mutation • MYD88 L265P • MYD88 wild-type
    |
    Imbruvica (ibrutinib) • Brukinsa (zanubrutinib)
    12ms
    Next-Generation Sequencing of Vitreoretinal Lymphoma by Vitreous Liquid Biopsy: Diagnostic Potential and Genotype/Phenotype Correlation. (PubMed, Invest Ophthalmol Vis Sci)
    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.
    Journal • Liquid biopsy • Next-generation sequencing • Biopsy
    |
    CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • IGH (Immunoglobulin Heavy Locus) • ETV6 (ETS Variant Transcription Factor 6) • IL6 (Interleukin 6) • IL10 (Interleukin 10) • PIM1 (Pim-1 Proto-Oncogene) • IGLL5 (Immunoglobulin Lambda Like Polypeptide 5)
    |
    MYD88 mutation • MYD88 L265P
    |
    LymphoTrack® Dx IGH Assay • LymphoTrack® Dx IGK Assay
    12ms
    IRAK-4 inhibition: emavusertib for the treatment of lymphoid and myeloid malignancies. (PubMed, Front Immunol)
    These data suggest that the anti-leukemic activity of IRAK-4 inhibition can be exploited in relapsed/refractory (R/R) AML/MDS. In this review article, we discuss the currently available pre-clinical and clinical data of emavusertib, a selective, orally bioavailable IRAK-4 inhibitor in the treatment of R/R B-cell lymphomas and myeloid malignancies.
    Review • Journal
    |
    MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • SF3B1 (Splicing Factor 3b Subunit 1) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • IRAK4 (Interleukin 1 Receptor Associated Kinase 4)
    |
    SF3B1 mutation • MYD88 L265P • U2AF1 mutation
    |
    emavusertib (CA-4948)
    1year
    Anterior segment involvement in vitreoretinal lymphoma: clinical manifestations, molecular findings and in vivo confocal microscopy. (PubMed, Br J Ophthalmol)
    Anterior segment manifestations are often present in VRL and include dendritiform and dust-like keratic precipitates. IVCM in VRL can identify different patterns associated with keratic precipitates. MYD88 L265P mutation in the aqueous humour of VRL patients can also be found in eyes without significant anterior segment involvement.
    Preclinical • Journal
    |
    MYD88 (MYD88 Innate Immune Signal Transduction Adaptor)
    |
    MYD88 L265P
    1year
    Clinical Characteristics, Treatment Approach and Long-Term Outcomes of 678 Patients with Symptomatic Waldenstrom's Macroglobulinemia: Comprehensive Insights from a Spanish Registry of IgM Gammapathies (ASH 2023)
    The main first-line treatment regimens received were: chlorambucil (37%), dexamethasone, rituximab and cyclophosphamide (DRC)(21%), rituximab monotherapy (13%), bendamustine/rituximab (BR) (9.1%), Bruton tyrosine kinase (BTK) inhibitors (7%), and bortezomib, dexamethasone and rituximab (BDR) (5.5%). There were no significant differences in OS between different times of diagnosis. This Spanish registry for SWM contributes to advancing knowledge and the continual enhancement of treatment strategies for WM.
    Clinical
    |
    MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • CXCR4 (Chemokine (C-X-C motif) receptor 4) • PRAME (Preferentially Expressed Antigen In Melanoma)
    |
    MYD88 L265P • CXCR4 mutation
    |
    Rituxan (rituximab) • bortezomib • cyclophosphamide • dexamethasone • bendamustine • Leukeran (chlorambucil)
    1year
    Lymphoplasmacytic Lymphoma: An Atypical Presentation with IgG Monoclonal Gammopathy (ASH 2023)
    He received one cycle of CyBorD (Cyclophosphamide, Bortezomib, Dexamethasone), followed by seven cycles of KCD (Carfilzomib, Cyclophosphamide, Dexamethasone) and Rituximab...The patient was treated with Acalabrutinib, and his anemia, epistaxis, and coagulopathy resolved...In contrast to our patient, who has LPL with IgG Monoclonal gammopathy, approximately 95 percent of LPL patients have IgM Monoclonal gammopathy, which corresponds with WM. As a result, clinicians should be on the lookout for LPL that lacks an IgM Monoclonal Paraprotein.
    IO biomarker
    |
    CD20 (Membrane Spanning 4-Domains A1) • MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • CXCR4 (Chemokine (C-X-C motif) receptor 4) • CD38 (CD38 Molecule) • PTPRC (Protein Tyrosine Phosphatase Receptor Type C) • NCAM1 (Neural cell adhesion molecule 1) • CD5 (CD5 Molecule) • SDC1 (Syndecan 1) • MME (Membrane Metalloendopeptidase) • ITGAX (Integrin Subunit Alpha X) • FCER2 (Fc Fragment Of IgE Receptor II)
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    CD20 positive • MYD88 mutation • MYD88 L265P • CXCR4 mutation • CD38 positive • SDC1 positive
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    Rituxan (rituximab) • bortezomib • cyclophosphamide • Calquence (acalabrutinib) • carfilzomib
    1year
    Trial in Progress: An Open-Label Expansion Trial Evaluating the Safety, PK/PD, and Clinical Activity of Emavusertib (CA-4948) + Ibrutinib in R/R Primary CNS Lymphoma (ASH 2023)
    Key exclusion criteria: intraocular PCNSL without brain lesion or CSF involvement or significant co-morbidity. Key clinical assessments include brain imaging, CSF- and ocular examinations.
    Clinical • PK/PD data • IO biomarker
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    FLT3 (Fms-related tyrosine kinase 3) • MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • IRAK4 (Interleukin 1 Receptor Associated Kinase 4)
    |
    MYD88 L265P
    |
    Imbruvica (ibrutinib) • emavusertib (CA-4948)