MYC rearrangement + BCL2 rearrangement

The patient received molecularly guided therapy with Pola-R-CHP (polatuzumab vedotin, rituximab, cyclophosphamide, doxorubicin, prednisone) plus venetoclax, achieving complete metabolic remission. Due to the persistent MEF2B and TET2 mutations in ctDNA indicated MRD positive, which prompted she received consolidative CAR-T therapy (axicabtagene ciloleucel)...The BCL2 inhibitor venetoclax has shown good therapeutic effects on DLBCL overexpressing BCL2. An integrated approach incorporating these strategies may improve outcomes for this rare lymphoma subtype.

In 2015, BC Cancer introduced a provincial guideline recommending dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (DA-EPOCH-R) for fit patients aged £75 years with HGBCL-DH-BCL2 identified by routine cytogenetic testing. In a contemporary cohort of HGBCL-DH-BCL2 histologically transformed from follicular lymphoma in the DA-EPOCH-R era, outcomes of chemoimmunotherapy-naïve patients were comparable to those with de novo disease, whereas patients treated with chemoimmunotherapy for follicular lymphoma prior to transformation had poor outcomes. These data support using DA-EPOCH-R in select patients with HGBCL-DH-BCL2 of DLBCL morphology.

P3, N=6430, Recruiting, Mats Heyman | Trial completion date: Jun 2032 --> Jun 2033 | Trial primary completion date: Jun 2027 --> Jun 2033

In conclusion, molecular testing enables a subset of HGBCL-NOS to be assigned to established categories. Based on rarity and diagnostic challenges, broader inclusion of HGBCL-NOS should be considered in biomarker-driven DLBCL trials.

The outcome of B-ALL with t(14;18)(q32;q21) is poor. Incorporating immune-therapies, chimeric antigen receptor (CAR)-T cell therapy, with or without HSCT, into the treatment regimens, might further improve outcomes.

Based on rarity and diagnostic challenges, broader inclusion of HGBCL-NOS should be considered in biomarker-driven DLBCL trials. Molecular analyses reveal that HGBCL-NOS encompasses a heterogeneous collection of tumors.A subset of HGBCL-NOS can be assigned to established molecular groups, while others remain unclassified.

Our results suggest that an integrated NGS strategy should not replace FISH or be routinely used in the workup to detect the clinically relevant rearrangements in HGBCL. It may serve as a complement to FISH testing when FISH shows negative results.

Our study demonstrates that our local population has similar clinicopathological and prognostic characteristics of DLBCL as compared to global findings. It also highlights the limitations of R-CHOP(-like) regimens in contemporary DLBCL management and therefore an ongoing need for improved therapeutic strategies.

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.

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.

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.

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.