Venclexta (venetoclax)

Undetectable minimal residual disease (uMRD) has emerged as a critical prognostic and potentially predictive biomarker in chronic lymphocytic leukemia (CLL), particularly in venetoclax-based time-limited regimens...Ongoing trials will further define the role of MRD-adapted therapy duration in first-line CLL treatment. Overall, MRD is a powerful tool to move beyond one-size-fits-all regimens and may become integral in personalizing CLL management across diverse therapeutic regimens.

P1, N=50, Active, not recruiting, Dana-Farber Cancer Institute | Recruiting --> Active, not recruiting | Trial primary completion date: Dec 2025 --> Feb 2025

P=N/A, N=100, Active, not recruiting, AbbVie | Recruiting --> Active, not recruiting

P2, N=400, Not yet recruiting, Australasian Leukaemia and Lymphoma Group (ALLG) | Phase classification: P --> P2 | N=50 --> 400

In vitro treatment of primary HRS cells with BCL2 inhibitor, venetoclax, augmented induction of apoptosis in HRS cells and other cells of the HL immune microenvironment. These findings support further study of targeting apoptosis resistance as a potential approach to eliminate malignant HRS cells and dismantle inflammatory lesion formation in pediatric HL.

This review compared the efficacy and safety of low-dose cytarabine (LDAC), azacitidine (AZA), 5- and 10-day decitabine (DEC), and gemtuzumab ozogamicin, alone or combined with drugs such as venetoclax (VEN), in older adults with AML ineligible for conventional chemotherapy. Treatment decisions should consider patient goals and functional status. These findings informed eight recommendations in updated ASH-AML guidelines.

Among the combination regimens tested, cytarabine or hypomethylating agents (HMA) drive strong blast reduction in patient samples previously exposed to venetoclax and yield improved survival in AML patient-derived xenograft models with prior venetoclax/5-azacytidine treatment. These preclinical findings support the clinical evaluation of dual BCL-2/BCL-XL inhibition in AML patients, particularly, those who do not respond to venetoclax.

Venetoclax combination regimen achieved excellent efficacy and safety in the treatment of relapsed/refractory multiple myeloma with t(11;14) in this case. The treatment of patients with relapsed and refractory multiple myeloma with t(11;14) by venetoclax still needs to be confirmed by more clinical studies.

This approach is demonstrated in the recent promising results achieved utilizing venetoclax, a BCL2 inhibitor, in patients with PICALM::MLLT10 acute leukemia. Herein, we provide updates on the pathophysiology, clinical presentation, prognosis, and treatment of PICALM::MLLT10 acute leukemia.

The B-cell lymphoma 2 (BCL-2) inhibitor venetoclax (VEN) in combination with hypomethylating agents (HMAs) has improved treatment outcomes for acute myeloid leukemia (AML) patients unfit for intensive chemotherapy and is increasingly used in the relapsed/refractory setting. Ex vivo treatment with the combination of navitoclax and SMAC mimetics further enhanced the eradication of VEN-HMA refractory blasts, although toxicity was also observed in healthy CD34+ cells. In conclusion, our integrative analysis identifies molecular signatures associated with primary VEN-HMA resistance and highlights BCL-2/BCL-XL inhibition and SMAC mimetics as therapeutic strategies to target resistance.

This study demonstrates, for the first time, the successful targeting of mCALR with CAR-T cells as a therapeutic strategy for MPNs. The chosen construct shows strong preclinical efficacy against established cell lines and patient-derived cells. Additionally, transcriptomic profiling uncovered apoptosis resistance mechanisms and supports a combination strategy with BH3 mimetics, such as venetoclax. These findings provide a compelling rationale for ongoing preclinical development and future clinical application of anti-mCALR CAR-T cells for the treatment of MPNs.

Two doxorubicin-resistant leukemia cell lines were established. Mechanistically, this dual-targeting regimen concurrently attenuated both the Nrf2-mediated antioxidant defense and the pro-survival PI3K/AKT signaling axis, which collectively underpin its enhanced anti-leukemic efficacy. This study demonstrates venetoclax combined with ML385 overcomes chemotherapy resistance in acute myeloid leukemia by modulating Nrf2/ARE-mediated oxidative stress.These findings reveal a novel mechanism and a promising therapeutic strategy.