Non-Hodgkin’s Lymphoma

Emavusertib in combination with anti-PD-1 therapy results in improved tumor-infiltrating lymphocyte recruitment, decreased myeloid derived suppressor cell function, and upregulation of interferon γ signaling resulting in improved survival in aggressive mouse models of melanoma brain metastases. This work supports the development of combination strategies of emavusertib with immune checkpoint blockade in melanoma brain metastases.

Conflicting reports show that it is a biomarker for response to cisplatin and a prognostic factor in some brain tumors, such as medulloblastomas, but can even be a negative prognostic factor in others, like glioblastomas...In brain tumors such as medulloblastomas and primary central nervous system lymphomas (PCNSL), when total cell killing can be expected by chemotherapy and/or chemoradiotherapy, high SLFN11 expression is a positive prognostic marker. However, SLFN11 can also be highly expressed in mesenchymal tumors, and in cases where total cell killing cannot be achieved, widespread relapse can accompany an initial response.

Here, we describe X-LYMPH (Xenografts of Lymphoma), a publicly available and molecularly annotated PDX repository that captures the heterogeneity of LBCL. X-LYMPH includes models of CAR T-cell resistance, providing a shared foundation for mechanistic research and therapeutic development for lymphomas.

In addition, the expression of c-Myc and IRF9 in the liver, and c-Myc and BCL-2 in the spleen was modulated in a pregnancy-stage-specific manner. In summary, pregnancy modulated the expression of JAK/STAT members in maternal liver and spleen in a pregnancy-stage- and tissue-specific manner, which may contribute to the maternal immunotolerance and increases of spleen and liver sizes during gestation.

Among patients with heavily pretreated B-cell non-Hodgkin lymphoma, a single infusion of tisagenlecleucel led to decade-long remissions (lymphoma-free survival) in approximately one third of the patients with large B-cell lymphomas and in nearly one half of those with follicular lymphoma. (Funded by the Richard Berman Family Innovations Center in CLL and Lymphomas and others; ClinicalTrials.gov number, NCT02030834.).

P1, N=20, Recruiting, Huda Salman | Trial completion date: Dec 2041 --> Dec 2042 | Trial primary completion date: Dec 2026 --> Dec 2027

P=N/A, N=0, Withdrawn, Stanford University | N=20 --> 0 | Not yet recruiting --> Withdrawn

Apart from treating promptly the underlying trigger conditions, earlier incorporation of targeted anti-cytokine therapy such as anakinra is strongly favored these days. The cytotoxic etoposide shall be chiefly reserved for malignancy-associated HLH, including B-cell lymphomas, and refractory disease. Rituximab has led to superior outcomes when utilized to clear EBV-infected B-cell reservoirs...The anti-IFN-γ monoclonal antibody emapalumab has been approved for refractory HLH cases. The JAK 1/2 inhibitor ruxolitinib may prove useful in this space as well. The therapeutic arsenal is likely to evolve further in the direction of agents addressing specific pathophysiologic steps in asHLH. Targeting effector cytokines, their receptors, inflammasome pathways are promising future directions in asHLH therapeutics.

The SNP rs1800890 showed modest but significant associations with NHL risk in codominant 1 (OR = 1.12, p < 0.001), codominant 2 (OR = 1.06, p = 0.006), and recessive models (OR = 1.08, p = 0.002); rs1800896 showed weak significant associations with NHL risk in dominant (OR = 1.08, p = 0.001) and codominant 2 models (OR = 1.07, p = 0.006). Subgroup analysis based on ethnicity revealed a nominally significant protective association in Caucasians for rs1800871 in the allelic model (OR = 0.87, p = 0.038).

After 40 months, the patient remains free of GVHD, PID, and lymphoma relapse, demonstrating successful lymphoma control and correction of the underlying immunodeficiency, thereby highlighting the feasibility of haploidentical HSCT in these patients.

The procedure is well-tolerated, with manageable complications and favourable long-term outcomes. ASCT should be considered as a consolidation therapy for eligible HIV-positive patients with PBL, offering the potential for prolonged disease-free survival.

Positive C-MYC and EBV expression results point to a possible aetiology for B-cell lymphoma. We were unable to find any variations in the expression of EBV or C-MYC between the GCB and ABC groups. A large-scale, prospective investigation involving multiple institutions is necessary.