MYC rearrangement

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.

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.

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.

Similar results were obtained by combining Talazoparib and different PARP inhibitors with the alkylating agent cisplatin, indicating a class effect. Importantly, PBMC-derived T cells from healthy donors did not show any sign of DNA damage accumulation upon exposure to Lonca, Talazoparib and the combination. These data provide the rationale for future therapeutic strategies based on selective induction of DNA damage in neoplastic B cells in combination with DDR inhibition in aggressive MYC-positive B cell lymphoma.

This case highlights the complexities of understanding genetic susceptibility in childhood cancers. We propose a multifactorial oligogenic inheritance of cancer susceptibility in this patient through several mechanisms of genomic instability.

MYC rearrangements are relatively rare in B-ALL/LBL, and the identification of a "triple-hit" elicited an initial diagnostic dilemma. However, a multimodal approach allowed for the classification of this complex case and helped guide selection of an appropriate therapeutic regimen.

P1/2, N=107, Completed, National Cancer Institute (NCI) | Phase classification: P2 --> P1/2

Diffuse Large B-cell Lymphoma (DLBCL) represents a challenging disease as only 60% of DLBCL can be cured with R-CHOP...In conclusion, R-CODOX-M/IVAC may be a good first line treatment for younger patients with aggressive DLBCL. Figure 1.

With the limits of the small sample size our data suggest that B-ALL/NHL 2002 GMALL regimen has an acceptable safety profile, with excellent outcome in SHL and DHL/aDHL without BM involvement. ASCT consolidation could be considered in pts achieving CR, and early shift to alternative strategies such as CAR-T cell therapy should be considered in DHL/aDHL patients with BM involvement.

The current findings reveal the clinicopathologic and genetic features of HT-MZLs, suggesting that these tumors might constitute a group distinct from MZL and de novo non-GCB type DLBCL. TBL1XR1 mutations may be considered a predictor of HT in MZL.

Cytogenomic profile was concordant with the literature data, however the role of IGH rearrangement, 14q deletion and 5q35.2 gain need to be explored. We anticipate that further characterization of RT lesions will probably facilitate better understanding of the RT clonal evolution.

No abstract available

AR160 therapy is a novel drug delivery system incorporating significantly lower doses of paclitaxel and rituximab that is safe and demonstrates promising clinical activity in patients with low-grade and high-grade previously treated B-cell lymphomas. This principle of treatment is applicable to other disorders. Further clinical testing is warranted in these patient populations.

To strengthen the application of this technology into clinical practice, further analysis is being conducted for weighting and assigning of scores for each predictor variable. This would assist clinicians in making a precise diagnosis, complementing existing diagnostic modalities for EBL, and reducing the rate of misdiagnosis arising from diagnosis based on clinical suspicion and tissue morphology without immunohistochemistry.

Blood 2020, Varano et al. Nature 2017), which converge on a common phenotype and high-grade morphology (Figure 1B).

Introduction Co-expression of C-MYC and BCL2 in diffuse large b-cell lymphomas (DLBCL), also termed double-expressor lymphomas (DEL), has been shown to be associated with poorer outcomes after standard R-CHOP induction therapy...Conclusion Co-expression of C-MYC/BCL2 was associated with inferior outcomes after ASCT in patients with R/R DLBCL. While ASCT has been the standard curative approach in the R/R setting, considerations for novel targeting therapies to achieve a deeper response prior to transplant or the upfront use of chimeric antigen receptor T-cell therapy at first relapse may be further explored in this high-risk subset of patients.

2022 Feb 1; 40(4):369-381). Performance of CLMA on a larger number of tumor samples from DLBCL/HGBL pts subsequently treated with CART19, which is planned, may be informative.

23 (38%) vs 45 (33%) were treated with Tisa-cel and 90 (67%) vs 37 (62%) were treated with Axi-cel. Figure 2 Conclusion : CAR-T cell therapy used in third line or more seems to overcome the poor prognosis of HGBL subtypes as compared to other LBCL subtypes, all characterized with FISH. This observation supports the interest to evaluate the potential benefit of CAR-T earlier in the course of the disease.

In this cohort of older adults receiving treatment for DLBCL or double hit lymphoma, the vast majority felt it was important to know prognostic information over time and found that this information was helpful for decision making. Our finding that the majority estimated their likelihood of cure to exceed 75% despite most having aa-IPI scores indicating average cure rates < 60 suggests that older adults with newly diagnosed DLBCL hold overly optimistic views of their prognosis.

Introduction While comprehensive genomic analyses have identified genetic subgroups of diffuse large B cell lymphoma (DLBCL) when retrospectively performed on tumor biopsies (bx) from patients (pts) subsequently treated with R-CHOP (PMID 29713087, 29641966), it is unclear if these or similar assays can be applied in clinical practice...Conclusions TP53 mut identified through CLMA, specifically those resulting in LOF, predict for inferior clinical outcomes in pts with newly-diagnosed DLBCL/HGBL. Results of CLMA can be practically used to inform prognosis and/or identify pts for clinical trials investigating therapies targeting derangements caused by specific mut.