MYC translocation + BCL2 translocation

We identified a distinct high-risk DLBCL subgroup, characterized by MYC and BCL2 aberrations, beyond conventional DHL-BCL2 and DEL, and irrespective of cell-of-origin, thereby expanding the poor-prognosis group.

Relapsed/refractory LBCL remains radioresponsive with 60-80% response rate to RT. While DHL pathology does not appear to influence RT response, its presence is associated with higher rates of local recurrence, suggesting it may be more radioresistant.

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.

Older adults with aggressive NHL often experience improvement in QOL and other PROs with treatment, even across age and frailty categories. VES-13 score and CGA identify patient groups at high risk for early death and poor QOL trajectory, for whom novel therapies and supportive care interventions are warranted. Higher VES-13 score is also associated with higher risk of unplanned hospitalization.

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.

All patients were treated with anthracycline based therapy, with 94% receiving RCHOP and 6% receiving DA-EPOCH-R... These data both demonstrate the feasibility and the prognostic utility of ctDNA-MRD during and after SOC induction therapy for DLBCL in a real-world population using an ultrasensitive ctDNA-MRD assay. The higher predictive value and accuracy of detectable ctDNA-MRD as compared with PET/CT suggest opportunities for integration of such assays in lymphoma response criteria, to potentially inform future clinical decision making.

All patients received two cycles of R-CHOP-21 with HD-Mtx on day 15 and depending on the biological risk factors (C-MYC translocation, C-MYC and BCL2 translocation (double hit), 17p/TP53 deletion, co-expression of MYC and BCL2, P53+ and/or CD5+) either four additional courses of R-CHOEP-14 (no biological risk factors) or four courses of dose-adjusted EPOCH-R (biological risk factors). In addition, one course of R-HD-cytarabine was given to all patients... Intensified immunochemotherapy results in a favorable outcome in patients with high-risk LBCL apart from those with 17p/TP53 deletion, TP53 mutations and/or high ctDNA burden. Our findings highlight the role of ctDNA as a noninvasive biomarker with a potential to improve risk stratification beyond biological and clinical factors and to guide treatment decisions in patients with high-risk LBCL.

P1, N=20, Recruiting, Lapo Alinari | Trial completion date: Dec 2025 --> Mar 2027 | Trial primary completion date: Dec 2024 --> Mar 2027

P1, N=20, Recruiting, Lapo Alinari | Not yet recruiting --> Recruiting

P1, N=20, Not yet recruiting, Lapo Alinari

The presence of BCL2 mutations correlates with BCL2 translocations suggesting an AID-induced mechanism. The epitopes recognized by the antibodies are often affected by mutations in that region, therefore may lead to false negative IHC results using the 124/Ventana clone. Given the clinical significance of BCL2 expression in diagnosis and prognostication of FL and DLBCL, it is recommended that alternative antibodies, such as the E17 clone, be used to prevent false negative BCL2 protein expression.

Although differences were seen in COO and IPI scores, OS was not significantly different between racial groups in multivariable analysis except between White and Others patients . As the Others patients were a heterogenous group, in-depth study is warranted in the future to delineate true differences.

Introduction Dual translocation of MYC and BCL2 or the dual overexpression of these proteins in patients with aggressive B-cell lymphomas, termed double-hit lymphoma (DHL) and double expressing lymphoma (DEL), respectively, have worse outcomes after standard chemoimmunotherapy with R-CHOP...CNS prophylaxis was optional, and all 33/54 (61.1%) received IT methotrexate...Considering that the vast majority of relapses are expected in the first 24 months after therapy, these results are promising and warrant further study. The specific benefit attributable to LEN needs to be tested in a randomized setting.

Genomic data implicate TP53 and cell cycle dysregulation as contributors to the pathogenesis of tMZL, as is the case in tFL. ‘Hot’ and ‘cold’ tMZL TIME profiles were identified.

Despite variations in the cut-off values used to determine CD30 positivity in DLBCL, the expression of this protein seems to be associated with a higher survival rate and better prognosis.

Our data, which were based on morphological analysis, immunophenotyping and genotyping by FISH were in line with new concepts of LBCL taxonomy integrating genetic, phenotypical and immunological characteristics with identification of new subgroups where MYC-translocation and MYC/BCL2 DH may identify a noninflamed subtype. These findings may furthermore hold significant predictive value especially regarding immune checkpoint blockade therapy, but further molecular characterization should be done to substantiate this hypothesis.