Venclexta (venetoclax)

Finally, we highlight some of the ongoing studies that test quizartinib in patients with FLT3-ITD-positive AML, patients with FLT3-ITD-negative AML, in both the first-line and R/R settings, in patients fit or unfit for intensive chemotherapy, including studies for quizartinib-based combination with other compounds such as decitabine and venetoclax. Future research should aim to further optimize the clinical value of quizartinib and explore its use in additional clinical settings, which could be achieved by testing quizartinib with other drugs, better characterization of the mechanisms of resistance, identification of the role of quizartinib as a maintenance therapy after allo-HCT, and investigating quizartinib in patients with FLT3-ITD-negative AML.

He was administered alemtuzumab twice (at the time of initial treatment and relapse) and cyclophosphamide, vincristine, and hydrocortisone chemotherapy. Furthermore, novel therapeutic drugs (venetoclax and tofacitinib) were administered based on previous case reports...Consideration should be given to suspending treatment, adjusting the administration interval, or administering G-CSF if necessary. The treatment interval can be appropriately adjusted, making it a valuable treatment option for refractory T-PLL.

The VIPAAY peptide from the soybean β-conglycinin β subunit showed the highest potential to interact with Bcl-2, comparable to Venetoclax, a well-known anticancer drug. Further experiments are needed to confirm this study's findings.

P1/2, N=20, Not yet recruiting, Benjamin Tomlinson | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Dec 2024 --> Dec 2025

P2, N=75, Completed, University of Nebraska | Active, not recruiting --> Completed | Trial primary completion date: Oct 2024 --> Mar 2024

To address this, we investigated the effects of etoposide, temozolomide, 5-azacitidine, and venetoclax on healthy BM-derived MSC functionality. Our findings show that besides HSPC, also MSC are sensitive to certain antineoplastic agents, resulting in molecular and functional alterations that may contribute to therapy-related myelosuppression. Understanding these interactions could be helpful for the development of strategies to preserve BM MSC functionality during different kinds of anticancer therapies.

Our findings suggest the addition of HHT to VA might enhance response and mitigate the negative impact of certain genetic patterns in RR-AML while being well tolerated.

P2, N=15, Active, not recruiting, Bnai Zion Medical Center | Recruiting --> Active, not recruiting | Trial primary completion date: Mar 2024 --> Dec 2024

P2, N=36, Active, not recruiting, University of Colorado, Denver | Recruiting --> Active, not recruiting

P2, N=59, Recruiting, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine

P=N/A, N=83, Recruiting, Affiliated Hospital of Nantong University | Not yet recruiting --> Recruiting

P=N/A, N=15, Recruiting, The First Hospital of China Medical University; The First Hospital of China Medical University

P=N/A, N=181, Completed, The First Affiliated Hospital of Anhui Medical University; The First Affiliated Hospital of Anhui Medical University

P=N/A, N=15, Not yet recruiting, Zhejiang Provincial People's Hospital; Zhejiang Provincial People's Hospital

P=N/A, N=56, Not yet recruiting, The First Affiliated Hospital,Sun Yat-sen University; The First Affiliated Hospital,Sun Yat-sen University

P4, N=40, Not yet recruiting, General Hospital of Chinese People's Liberation Army Northern Theater Command; General Hospital of Chinese People's Liberation Army Northern Theater C

P4, N=180, Not yet recruiting, Qilu Hospital of Shandong University; Qilu Hospital of Shandong University

P2, N=67, Recruiting, The First Affiliated Hospital, Zhejiang University School of Medicine; The First Affiliated Hospital, Zhejiang University School of Medicine

P2, N=101, Active, not recruiting, Gruppo Italiano Malattie EMatologiche dell'Adulto | Recruiting --> Active, not recruiting | Trial completion date: May 2024 --> Apr 2026 | Trial primary completion date: May 2024 --> Oct 2024

P1, N=17, Active, not recruiting, Peter MacCallum Cancer Centre, Australia | Trial primary completion date: Jun 2024 --> Jun 2025

P1, N=30, Suspended, City of Hope Medical Center | Recruiting --> Suspended

P2, N=164, Active, not recruiting, Takeda | Trial completion date: Sep 2024 --> Dec 2024

The combination of the Bruton tyrosine kinase inhibitor (BTKi) ibrutinib, the BCL-2 inhibitor venetoclax (V), and the anti-CD20 monoclonal antibody (mAb) obinutuzumab (O) has demonstrated safety and efficacy in R/R and TN MCL (Le Gouill, Blood 2021). AVO is safe and active in pts with R/R and TP53-aberrant/transplant ineligible TN MCL. Preliminary efficacy and feasibility of an MRD-guided treatment approach is encouraging in this high-risk TN cohort B. Our data supports further investigation of a targeted triplet approach, and the phase II TN transplant eligible and TP53 wild type cohort is enrolling based on demonstrated safety and efficacy in cohort B. Updated results will be presented at the meeting.

Background The only FDA-approved therapy for systemic light chain (AL) amyloidosis is daratumumab plus cyclophosphamide, bortezomib, and dexamethasone (i.e., Dara-CyBorD)...At the time of the MRD test, 30 (58.8%) patients were on active surveillance, 10 (19.6%) were on daratumumab and 9 (17.6%) on venetoclax...In patients with relapsed AL, MRD negativity is correlated with a better hematological response and could potentially play a role in clinical trial design. The impact of gender on MRD status remains an important area for further study.

Zanubrutinib is a second-generation BTKi with superior PFS and safety compared with ibrutinib (Brown NEJM 2023). Five-year follow up of the BOVen regimen demonstrates frequent uMRD4 in PB (96%) and BM (92%), and uMRD4 was durable with a median MRD4-free survival of 34 mo. Retreatment with zanubrutinib-venetoclax was also well-tolerated and effective. A phase 2 trial of BOVen with ΔMRD400-directed treatment duration is ongoing.

Responses are durable, with 89%, 87%, and 77% 4-yr PFS in all-comer, uIGHV, and TP53 aberrant pts. Our data support further study of AVO for pts with TN high risk CLL in GCLLSG CLL16 and future trials.

VO is highly effective and feasible in both academic and community settings. The ability of obi to debulk patients prior to ven initiation allowed most patients to receive ven initiation in the outpatient setting. TLS is rare and was only seen secondary to obi.

Background: Venetoclax (ven) with azacitidine (aza) is the standard of care for newly diagnosed AML patients who are unfit for intensive induction chemotherapy. CC-486 (oral azacitidine) and ven is an all-oral regimen currently being investigated for the treatment of ND and R/R AML. The phase I portion of this study previously showed the MTD of CC-486 with ven to be 300mg d1-14 (Amaya et al. 2023).

ViPOR-P is safe without notable additional toxicity, especially neutropenia and neuropathy, compared to ViPOR, and DL3 was identified as the RP2D. Most AEs were hematologic and manageable with G-CSF with rare febrile neutropenia observed. Fixed-duration ViPOR-P x 6C without maintenance resulted in durable CRs, especially in pts with non-GCB DLBCL by IHC and ABC DLBCL by RNA-seq, including refractory and post-CAR-T pts.

Among the LIT treated patients, 96 patients received treatment with an IDH inhibitor, and 237 patients received a hypomethylating agent (HMA) plus venetoclax... A total of 1023 patients with ND AML were identified. Patients had a median age of 72 (range 60-92) years and the majority were non-Hispanic White (83.2%), and male (57.6%). Ninety-nine (9.7%) patients were IDH1MUT, 193 (18.9%) patients were IDH2MUT including 10 (1.0%) patients with a co-occurring IDH1 and IDH2 gene mutations.

Fixed-duration ViPOR x 6C without maintenance achieved CR in 100% and uMRD in 97% of MCL pts, with ongoing CR in 95% and 73% of TN and R/R pts, respectively, and only 1 R/R pt receiving consolidative allo-HSCT. This includes blastoid, TP53 mutated, and post-BTKi high-risk subsets. ViPOR with a 12d VEN ramp-up on C2 is safe in MCL pts of all ages without significant TLS or febrile neutropenia.

Introduction: Combined treatment with covalent BTK-inhibitor (cBTKi), such as ibrutinib, acalabrutinib, or zanubrutinib with BCL2-inhibitor, venetoclax, +/- CD20 monoclonal antibody obinutuzumab showed high rates of undetectable MRD (U-MRD4, 10-4 sensitivity) remission in patients (pts) with CLL (Jain, NEJM 2019; Munir NEJM 2023; Wierda, JCO 2021; Kater, NEJM Evidence 2022). We report results of combined pirtobrutinib, venetoclax, and obinutuzumab in pts with previously untreated CLL. We observed a very high rate of BM U-MRD6 at 6-months and 12-months of combined treatment. Adverse event profile was similar to what was noted in previous studies with these agents.

This study supports the use of MRD testing to guide duration of Ven / Obin therapy in the 1L setting. Early discontinuation of Ven/Obin for pts who are uMRD6 at C9 achieves similar PFS to pts who completed 12C of Ven/Obin and have uMRD5 status before entering TFO. In this study, concordance rate between PB and BM was relatively low (approximately two-thirds concordance) at 10-6 (C9) and 10-5 (C12) sensitivities.

P1/2, N=74, Active, not recruiting, ECOG-ACRIN Cancer Research Group | Recruiting --> Active, not recruiting

P1/2, N=84, Ongoing, Fundación Pethema

P2, N=622, Recruiting, Genmab | Trial completion date: Jun 2031 --> Nov 2032 | Trial primary completion date: Jun 2031 --> Nov 2032

P2, N=100, Not yet recruiting, VA Office of Research and Development | Trial completion date: Dec 2029 --> Dec 2030 | Trial primary completion date: Jun 2029 --> Jun 2030

P1/2, N=35, Active, not recruiting, St. Jude Children's Research Hospital | N=98 --> 35 | Trial completion date: Jul 2029 --> Mar 2025 | Trial primary completion date: Aug 2025 --> Jun 2024

We found that quercetin increased Bcl-2-associated X protein (Bax) expression in KG-1. Our study provides a novel function for quercetin and presents a promising strategy for AML treatment using venetoclax.

Ex-vivo studies confirmed higher efficacy of BTX-A51 on RUNX1 -mutated myeloblasts and demonstrate synergy with azacitidine and venetoclax. Although the overall efficacy was modest, this study lays the groundwork for future studies with improved patient selection and combination approaches.

Moreover, a noteworthy decrease in the tumor volume was noticed in the mice treated with TNPs along with lower serum toxicity biomarker levels compared to the free drugs. Overall, the developed TNPs proved to be a promising and safer strategy for inducing triple-hit action in TNBC management.

Drug-resistant B-ALL cell lines could be successfully established by exposing RS4;11 cell line to the ascending concentration of BCL-2 inhibitors, and the drug resistance mechanism may be related to the overexpression of EP300.