MYC overexpression + BCL2 overexpression

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.

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.

These cell lines serve as a preclinical tool to test novel therapeutic strategies and develop a deeper understanding of the molecular mechanisms driving lymphomagenesis, therapeutic response, and resistance in genetically defined subtypes of GC-derived B-cell lymphomas. Most importantly, this resource meets a critical need in the field for syngeneic models of lymphoma to study disease progression and precision therapy in immunocompetent mice.

We assessed whether high BCL2/MYC co-expression by RNA sequencing could identify a patient subset responsive to ibrutinib using baseline biopsies from the PHOENIX trial (NCT01855750), which evaluated the addition of ibrutinib to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in untreated non-GCB DLBCL. Consequently, high BCL2/MYC co-expression identifies a subset of non-GCB DLBCL that may be preferentially responsive to ibrutinib and warrants further investigation. ClinicalTrials.gov NCT01855750.

The first-line therapy was categorized into two groups, R-CHOP, and intensive induction therapy (R-EPOCH, R-hyperCVAD, and R-CODOX-M/R-IVAC)...The CL+ group represents a potentially high-risk patient population and needs to be prioritized for experimental and cellular therapies at first relapse. Future prospective studies should include testing for CL and validate the findings found in our study.

No abstract available

Conclusion Multivariate analyses support the benefit of Pola-R-CHP in patients with BCL2+ and MYC+ DLBCL. The poor prognostic impact associated with DEL, which was mainly driven by BCL2+, appears reduced in Pola-R-CHP- vs R-CHOP-treated patients.

Copanlisib as single agent has been already shown a moderate activity in DLBCL and the association Copa-RB plus copanlisib maintenance could be a new treatment option to improve the outcome of these patients. Biomarkers studies may further elucidate patients who are more likely to respond to this treatment.

Adjusted hazard ratio (HR) was 2·28 [95% confidence interval (CI) 0·89-5·86, p = 0·086] and 4·05 (95% CI 1·37-11·97, p = 0·011) for FFS and OS, respectively. In this series of young DLBCL patients, TP53 gene mutation identified a poor prognosis subgroup, regardless of treatment and other biological markers.

Here, we synthesized and tested seven novel BCL2i in DLBCL cells with deregulated BCL2, and splenic marginal zone lymphoma (SMZL) cell lines with acquired resistance to idelalisib, copanlisib or ibrutinib. Using in silico-based drug design complemented by classical and kinetic target-guided synthesis (KTGS) led to the synthesis of seven potential BCL2 inhibitors (BCL2i). We report the in vitro anti-lymphoma activities of novel BCL2i, particularly ST-65, in DLBCL and SMZL cells. Our results suggest that these compounds are structures further exploitable for the design of improved anti-lymphoma drugs.Acknowledgements: The research work was supported by the Hellenic Foundation for Research and Innovation (H.F.R.I.) under the “First Call for H.F.R.I. Research Projects to support Faculty members and Researchers and the procurement of high-cost research equipment grant” (Project Number: 991 to AGT).

Of note, no reductions were observed in NK cell viability or MYC levels within NK cells upon LF PRLR knockdown, suggesting that LF PRLR selectively kills B-lymphoblasts without negatively impacting NK homeostasis. Conclusion Our studies identify the specific knockdown of LF PRLR as a potentially safe and targeted strategy to prevent the onset of B cell malignancies in SLE patients and to treat flagrant DLBCL and B-ALL.

In addition, IHC does not effectively predict the MYC, BCL2 and BCL6 G/A detected by FISH. In conclusion, FISH remains the golden standard and should always be performed when a HGBL is suspected in order to identify entities with poor outcome, such as ‘DHL/THL’ and ‘Alternative DHL/THL’.

Copanlisib as single agent has been already shown a moderate activity in DLBCL and the association Copa-RB plus copanlisib maintenance could be a new strategy to improve the outcome of these patients. Biomarkers studies would further elucidate patients who are more likely to respond to this treatment.

It has been proved that cyclophosphamide, doxorubicin, vincristine, and prednisone plus rituximab show limited effects for DHL or DE-DLBCL, and the rituximab plus dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin seem to be efficacious for DHL. The novel therapy is urgently needed for clinical improvement in DHL and DE-DLBCL.

The standard treatment approaches have been either 3 cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone with rituximab (RCHOP), closely followed by involved field radiation (IFRT) based on SWOG S8736 and S0014, or 6 cycles of RCHOP based on extrapolation from the Mabthera International Trial (MInT) and advanced-stage DLBCL trials...NCTN study S1001 built on BC Cancer experience and prior SWOG study S0313 which demonstrated promising PFS with the radioimmunotherapy agent ibritumomab tiuxetan.9 Patients had stage I/II non-bulky (< 10 cm) disease as defined by PET...The best therapy for a minority of patients with positive interim PET scan needs to be studied further but could include radiation. Competing risks of death in older patients with limited-stage disease may require different means of measuring outcomes than traditional PFS.