P3, N=40, Active, not recruiting, Fujian Medical University Union Hospital

Our study found that inhibition of XPO1 is a promising modality in the treatment of MDS, especially when combined with Venetoclax, which could be a potential target for MDS therapy.

Our study identified cellular and molecular biomarkers, notably CD56, that predict resistance to Rux + Ven, but further work is needed to understand and validate their effect in AML. This trial was registered at www.clinicaltrials.gov as #NCT03874052.

Azacitidine/venetoclax is the standard treatment for patients with acute myeloid leukemia (AML) unfit for intensive chemotherapy. The potentiated antileukemic activity positions cobicistat as a promising complementary agent in AML therapy. This trial was registered at www.clinicaltrials.gov as NCT06014489.

He was initially treated with azacitidine and venetoclax but demonstrated disease progression. In the setting of a KMT2A::ELL fusion, therapy was transitioned to the menin inhibitor revumenib, resulting in short-term clinical stability and tolerability under continued supportive care.

P3, N=788, Not yet recruiting, Institute of Hematology & Blood Diseases Hospital, China

P1, N=17, Active, not recruiting, City of Hope Medical Center | Trial completion date: Apr 2026 --> Mar 2027 | Trial primary completion date: Apr 2026 --> Mar 2027

P1/2, N=8, Active, not recruiting, City of Hope Medical Center | Trial completion date: Feb 2026 --> Feb 2027 | Trial primary completion date: Feb 2026 --> Feb 2027

Multivariable and LASSO analyses identified independent risk factors: male gender (OR=3.28, p = 0.025), higher blast percentage (OR=1.03, p = 0.006), elevated baseline uric acid (OR=1.01, p = 0.011), IDH1/2 mutation (OR=4.86, p = 0.005), and a trend with venetoclax-based therapy (OR=7.52, p = 0.072)...Adequate urine output reduced TLS risk, while excessive positive fluid balance correlated with severe TLS (p = 0.046). Individualized fluid management and 72-hour intensive monitoring are critical for high-risk groups.

These findings highlight genomic context in shaping BH3 mimetic responses and point to rational combination of this class of drugs with anti-leukemic agents such as asparaginase.

Pharmacologic AC inhibition with the ceramide analog SACLAC enhanced single-agent venetoclax cytotoxicity and the venetoclax + cytarabine combination in AML cell lines with primary or acquired venetoclax resistance. Importantly, AC knockdown sensitized AML cells to venetoclax and induced NOXA protein accumulation, whereas NOXA knockdown protected against AC and BCL-2 cotargeting. Collectively, these findings demonstrate the efficacy of cotargeting AC and BCL-2, and rationalize targeting AC as a therapeutic approach for venetoclax-sensitive and -resistant AML.

P2/3, N=232, Enrolling by invitation, Guangdong Second Provincial General Hospital