MYC rearrangement

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.

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 algorithm rescued 2 and 1 MYCr cases included in score 1 from both series. In conclusion, we suggest that both approaches combining the interpretation of CD10/LMO2/MYC by immunohistochemistry are useful to screen for MYCr.

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.

TP53 and KMT2C mutations conferred inferior outcome (3-year EFS P < 0.05). Overall, MYC-R lymphomas in CAYA have a molecular profile similar to BL regardless of their high-grade or DLBCL morphology, whereas MYC-non-R has more heterogeneous genetic alterations closer to that of DLBCL.

In a single center real world retrospective analysis of R/R LBCL patients with available genomic data, polatuzumab based therapy may be less effective in patients with HGBL-NOS or MYC/BCL2 histology and MYC rearrangements, but not in patients with GCB COO LBCL without these features. Routine performance of more comprehensive pathologic analysis of tumors may inform the use of polatuzumab based therapy in patients with LBCL.

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.

P=N/A, N=200, Not yet recruiting, Fondazione Italiana Linfomi - ETS

In addition, we demonstrated that using this model as a pre-screening tool (with a false-negative rate of 0%), FISH testing would be avoided in 35% of cases. This work demonstrates the feasibility of developing a medical device to efficiently detect MYC gene rearrangement on HE WSI in daily practice.

Furthermore, comparing the prognosis between these two groups, AR-HGBL-11q showed a relatively favorable prognosis (P = 0.15), although the difference was not statistically significant. We analyzed this rare lymphoma entity in the HIV setting and highlighted the importance of integrating histomorphological and immunophenotypic features in its diagnosis and classification.

The addition of bortezomib, lenalidomide, or daratumumab might improve outcomes. Including PBL patients and their participation in prospective clinical trials is warranted.

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.

Relapsed DLBCL-NOS presenting in the ocular adnexa (n = 6) were all of non-GCB origin and frequently of MCD subtype (n = 3, 50%), presenting with a similar genetic profile as primary ocular adnexal DLBCL-NOS. These results provide valuable insights into genetic drivers in ocular adnexal DLBCL-NOS, offering potential applications in future precision medicine.

P1/2, N=130, Recruiting, National Cancer Institute (NCI) | Trial primary completion date: Mar 2024 --> Mar 2025

We concluded that both could be diagnosed as "DLBCL-NOS with MYC rearrangement" using the current pathologic classifications, 2022 International Consensus Classification (ICC) and World Health Organization Classifications of Haematolymphoid Tumors (WHO-HAEM5). This report illustrates diagnostic challenges and treatment dilemmas that may be encountered, particularly for adolescent and young adults (AYA).

Despite the recent advances in the treatment of PBL, the prognosis of PBL patients remains dismal. The objectives of this review are to summarize the current knowledge on the epidemiology, molecular profiles, clinical and pathological features, differential diagnosis, treatment strategies, prognostic factors, and potential novel therapeutic approaches in PBL patients.

In total, 169 patients were treated with R-CHOP, 10 with R-CHOP and intermediate-dose methotrexate, 19 with R-DA-EPOCH, and 16 with other regimens. The 5-year OS for DHL patients was 32.4% (95% CI 16.6-48.2%) while all three TH patients were deceased or lost to follow-up. Our analyses of real-life data disclose that the R-CHOP protocol with CNS prophylaxis is a successful and curative treatment for a substantial proportion of DEL patients.

FISH analysis of FFPE PT-NHLs detects genetic abnormalities, even in small specimens, in approximately 60% of cases. While BCL2 and BCL6 abnormalities are infrequent, MYC and 11q abnormalities were seen in 1/3 of tested cases. Interestingly, the classic 11q aberration was seen only in GC-DLBCLs (all patients alive), while extra copies were seen in non-GC cases (all patients with follow-up have died), including 2 EBV positive, suggesting different pathogenetic pathways with unique biologic behavior.

Strong p53 by IHC in more than 30% of neoplastic cells is a useful tool to screen TP53 mutations. In our series, aLBCL did not have significant concurrent alterations between p53 and MYC pathways.

P1, N=33, Recruiting, Medical College of Wisconsin | Trial completion date: May 2028 --> May 2026 | Trial primary completion date: May 2027 --> May 2026

P3, N=300, Recruiting, Nordic Lymphoma Group | N=200 --> 300 | Trial completion date: Feb 2026 --> Dec 2028 | Trial primary completion date: Feb 2023 --> Dec 2025

P2, N=97, Active, not recruiting, Stichting Hemato-Oncologie voor Volwassenen Nederland | Trial primary completion date: Oct 2023 --> Jan 2024

The incidence of MBCL with 11q abnormalities in children is low, clinical symptoms are mild, and progression is slow. The absence of MYC, BCL2, BCL6 rearrangements, C-MYC negative and 11q abnormalities on FISH is an important diagnostic indicator, and reducing the intensity of chemotherapy can improve prognosis.

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.

In conclusion, our results demonstrate an increased exhaustion in circulating T-cells of HGBL-MYC/BCL2 patients. Nonetheless, the overall intact peripheral T-cell and NK-cell functions in these patients emphasize the importance to investigate potential immune evasion in the microenvironment of MYC-rearranged lymphomas.

We identified 1,434 LS DLBCL patients with known MYC-R status diagnosed between 2014 and 2020, who received R-CHOP(-like) regimens using the Netherlands Cancer Registry, with survival follow-up until February 2022...In stage I DLBCL, however, survival outcomes are excellent irrespective of MYC-R status. This challenges the diagnostic assessment of MYC-R in stage I DLBCL patients.

P2, N=40, Recruiting, M.D. Anderson Cancer Center | Not yet recruiting --> Recruiting

A clonal evolution model involving multiple chromosomal translocations and mitotic recombination is postulated to account for the karyotype, FISH, and microarray results but leaves unresolved the exact order of the evolutionary changes.

Deletion of chromosome 13q14 was frequent. The PBL cases in Taiwan showed recurrent mutations involving JAK-STAT, RAS-MAPK, epigenetic regulation, and NOTCH signaling pathways, findings similar to that from the West.

She was treated with dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin and rituximab chemotherapy. Rituximab was discontinued owing to largely absent CD20 expression. Interim positron emission tomography-CT after three cycles revealed a complete response, and the patient completed six cycles of therapy.

Chromosome 1 structural abnormalities were the most prevalent, found in 65% of cases. The frequent presence of subclones and composite karyotypes underscored the genomic heterogeneity and instability in this cohort.

Consequently, lymphoma cells demonstrate nucleolar dysregulation via altered noncoding 5.8S ribosomal RNA processing. We find that a noncoding mutation acquired during lymphoma progression affects noncoding rRNA processing, thereby rewiring protein synthesis leading to oncogenic changes in the lymphoma proteome.

Background Maplirpacept (PF-07901801) is an anti-CD47 fusion protein constructed to enhance phagocytosis and antitumor activity via inhibition of CD47-mediated signaling. All patients should have adequate bone marrow, hepatic, and renal function (eGFR ≥45 mL/min) and ECOG performance status ≤2. Exclusion criteria include prior treatment with an anti-CD47 agent, prior anti-CD20xCD3 containing regimen, refractoriness to an obinutuzumab monotherapy containing regimen, prior allogeneic stem cell transplantation or autologous stem cell transplantation within 12 weeks prior to enrolment, high grade B-cell lymphoma with BCL2 and Myc rearrangement, active bacterial, viral, fungal, mycobacterial, parasitic, or other infection.

To confirm whether KPT330 effects the generation or degradation of LC3B-II, we used the late autophagy inhibitor chloroquine (CQ) to cells and observed the p62 protein level reduced and LC3B-II protein level increased with additional use of CQ compared with only KPT330 treatment ( Fig1, d). However, none synergistic effect was observed according to KPT330 combined with Cytarabine, Doxorubicin, Azacitidine, Decitabine, Rapamycin, Bortezomib, Duvelisib or Venetoclax, respectively ( Fig2, d). CONCLUSIONXPO1 Inhibitor, KPT330 can restrict nuclear export of autophagy-related proteins thus regulate autophagy and stabilize p53 function in TP53-mutated Burkitt's lymphoma cells, which revealed a promising treatment.

Regarding their survival, patients with TP53 pathway alterations should probably not be treated with the standard RCHOP chemo-immunotherapy. Instead, a more intensive immunochemotherapy regimen or novel strategies such as first-line bispecific antibodies or CARTCells might be considered.

Background: In the era of immune-targeted therapy represented by rituximab, despite improved remission and survival rates in patients with diffuse large B-cell lymphoma (DLBCL), central nervous system (CNS) relapse, occurring in some DLBCL patients after achieving remission, remains a clinical challenge. Zanubrutinib-containing regimens extended PFS and OS in relapsed DLBCL patients with CNS involvement.