Venetoclax-based regimens, combined venetoclax with either hypomethylating agents or low-dose cytarabine, have markedly improved treatment outcomes in elderly patients with acute myeloid leukemia (AML). Importantly, the combination of bortezomib and venetoclax significantly prolongs the survival of mice inoculated with venetoclax-resistant AML cell line harboring BAX mutations, which are commonly observed in relapsed AML following venetoclax-based regimens and confer resistance to venetoclax by inhibiting BAX-dependent apoptotic pathway. Collectively, this study provides a rationale for venetoclax-bortezomib combination as a potential strategy to overcome venetoclax resistance in certain AML subsets.

These findings underscore the potential of GNL as a hepatoprotective drug against cytarabine-induced hepatotoxicity, mediated by its antioxidant and anti-inflammatory effects through modulation of the PI3K/AKT and NF-κB pathways. Future research should investigate its therapeutic potential in alleviating chemotherapy-induced liver damage.

The combination of famciclovir and nerve block therapy substantially improves pain relief, reduces inflammatory responses, and enhances clinical outcome without increasing the risk of adverse events.

Using an unbiased approach, we identify Src-family kinase member LYN, and guanine nucleotide-binding protein G(i) alpha subunit proteins, GNAI1, GNAI2, and GNAI3 as novel binding partners of MSLN in AML and show that pharmacological or genetic inhibition of LYN signaling restores NOMO-1 cell sensitivity to Ara-C. Together, these findings demonstrate that MSLN functions as an oncogenic driver in AML and reveal a previously unrecognized MSLN-LYN signaling axis, the therapeutic targeting of which may enhance responses to chemotherapy.

Analysis of primary AML samples or cell lines revealed that BMPR1B and TAZ/TEAD but not YAP levels were higher after patient relapse or in cells resistant to cytarabine or venetoclax. Finally, using a 3D human bone marrow-like model, we showed that targeting BMPR1B or TAZ/TEAD in combination with cytarabine impaired persistence of AML primary cells within the AML niche. Future therapeutic approaches could involve BMPR1B and/or TAZ/TEAD targeting in the context of AML patients refractory to chemotherapy or after relapse.

P3, N=172, Active, not recruiting, Children's Cancer Group, China | Recruiting --> Active, not recruiting

The combination of Ara-C and IDA in AML patients has a risk of ineffective induction chemotherapy, which may be related to serum OPN and NLR values. High expression of serum OPN and elevated NLR value may increase the risk of ineffective induction chemotherapy. The combination of serum OPN and NLR can assist in improving the predictive value of Ara-C combined with IDA in AML patients.

All patients remained disease-free, with no events of measurable residual disease (MRD) positivity by flow cytometry or molecular analysis documented. These findings preliminarily confirm that venetoclax, cytarabine, and homoharringtonine-based cytoreductive therapy is a safe and effective bridging therapy for allo-HSCT in patients with refractory/relapsed AML and RUNX1::RUNX1T1 fusion gene.

Based on Chinese AML patients as the study base, this study identifies independent prognostic factors affecting relapse after cytarabine consolidation therapy, and proposes a predictive model to assess the risk of early relapse in AML patients after receiving cytarabine consolidation therapy. This may provide a reference for clinicians to guide personalized treatment.

All patients enrolled in phase II received induction and consolidation therapy with gilteritinib 120 mg/day plus chemotherapy (induction: ⩽2 cycles, idarubicin/cytarabine once-daily; consolidation: ⩽4 cycles, cytarabine twice-daily) followed by maintenance with gilteritinib 120 mg/day monotherapy (⩽26 cycles). Induction and consolidation with gilteritinib plus chemotherapy, and maintenance with gilteritinib monotherapy were well tolerated in ND patients in Asia with FLT3 mut+ AML and had favorable efficacy compared with historical data. This trial was registered with the ClinicalTrials.gov identifier NCT02310321.

P3, N=180, Recruiting, SymBio Pharmaceuticals | Not yet recruiting --> Recruiting

In the presence of i.v. or topical ganciclovir (GCV), HSV-TK.007 acted to block VV replication either systemically or topically for control of skin lesions and shedding, respectively...In summary, the addition of HSV-TK.007 to an i.v. oncolytic VV enabled on-demand inhibition of systemic viral replication, skin lesions, environmental shedding, and systemic real-time non-invasive imaging of replication. A phase 1-2 clinical trial was initiated with this i.v. oncolytic VV expressing HSV-TK.007.