Venetoclax: A new wave in hematooncology

Mihályová, Jana; Jelı́nek, Tomáš; Growková, Kateřina; Hrdinka, Matouš; Šimíček, Michal; Hájek, Roman

doi:10.1016/j.exphem.2018.02.002

Cited by 81 publications

(62 citation statements)

References 127 publications

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“…Venetoclax is a small-molecule inhibitor of anti-apoptotic B-cell lymphoma 2 [29]. Combination regimens of venetoclax plus LDAC or HMAs have demonstrated promising activity in newly diagnosed, older patients with AML who are unfit for intensive chemotherapy [30,31].…”

Section: Venetoclax (Venclyxto/venclexta R )mentioning

confidence: 99%

How I treat newly diagnosed acute myeloid leukemia in an outpatient setting: a multidisciplinary team perspective

et al. 2020

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Historically, patients with acute myeloid leukemia received intensive chemotherapy requiring hospitalization, which can diminish quality of life and increase healthcare costs. The introduction of new therapies facilitated a shift toward outpatient therapy, which requires coordination of a multidisciplinary team, thorough patient evaluation, careful preparation and rigorous patient monitoring. Many patients are candidates for multiple treatment approaches; we generally employ CPX-351 (Vyxeos®) as an intensive outpatient approach and venetoclax (Venclyxto/Venclexta®) plus hypomethylating agents as a lower-intensity approach, with 2–3 visits/week during treatment. Treatment infusions are scheduled in the morning to leave sufficient time for transfusions and other supportive care later the same day, to prevent additional visits. With careful planning and patient monitoring, acute myeloid leukemia treatment can be successfully administered in the outpatient setting.

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Section: Venetoclax (Venclyxto/venclexta R )mentioning

confidence: 99%

How I treat newly diagnosed acute myeloid leukemia in an outpatient setting: a multidisciplinary team perspective

et al. 2020

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“…[4] The orally available analogue, ABT-263 (navitoclax), also triggers platelet apoptosis and is associated with doselimiting thrombocytopenia [5]. In contrast, , which is more selective for Bcl-2 over Bcl-xL, spares platelets and has been approved for treatment of chronic lymphocytic leukemia [6,7]. It is therefore important to understand which drugs trigger apoptosis in platelets.…”

Section: Introductionmentioning

confidence: 99%

Comparison of putative BH3 mimetics AT-101, HA14-1, sabutoclax and TW-37 with ABT-737 in platelets

Hao

Harper

2020

Platelets

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Platelet lifespan is regulated by intrinsic apoptosis. Platelet apoptosis can be triggered by BH3 mimetics that inhibit the pro-survival Bcl-2 family protein, Bcl-xL. Here, we investigated several small molecules that are reported to act as BH3 mimetics and compared their effects to the well-established BH3 mimetic, ABT-737. Platelet phosphatidylserine (PS) exposure was determined by flow cytometry. Changes in cytosolic Ca 2+ signaling were detected using Cal-520. Plasma membrane integrity was determined by calcein leakage. The roles of caspases and calpain in these processes were determined using Q-VD-OPh and calpeptin, respectively. As previously reported, ABT-737 triggered PS exposure in a caspase-dependent manner and calcein loss in a caspase and calpain-dependent manner. In contrast, AT-101 and sabutoclax triggered PS exposure independently of caspases. HA14-1 also triggered PS exposure in a caspase-independent but calpain-dependent manner. There were also significant differences in the pattern and protease-dependency of cytosolic Ca 2+ signaling in response to these drugs compared to ABT-737. Since there are clear differences between the action of ABT-737 and the other putative BH3 mimetics investigated here, AT-101, HA14-1 and sabutoclax cannot be considered as acting as BH3 mimetics in platelets. Furthermore, the platelet death caused by these drugs is likely to be distinct from apoptosis.

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“…Moreover, Morschhauser et al observed that RRMCL patients treated with obinutuzumab, a third‐generation, humanized anti‐CD20 monoclonal antibody, had an ORR of 27%. Venetoclax is a novel selective B‐cell leukemia/lymphoma‐2 (BCL‐2) inhibitor . In a phase 1 trial of venetoclax monotherapy in patients with RRMCL, Davids et al observed an ORR of 75%, which was obviously higher than that in patients treated with temsirolimus (ORR 22%) or lenamidomide (ORR 28%), and venetoclax was generally well tolerated .…”

Section: Introductionmentioning

confidence: 99%

Obinutuzumab and venetoclax induced complete remission in a patient with ibrutinib‐resistant non‐nodal leukemic mantle cell lymphoma

Zhou

Steinhardt

Düll

et al. 2020

European J of Haematology

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We herein report the case of a 73‐year‐old male patient who was diagnosed with leukemic non‐nodal MCL. This patient had received six cycles of bendamustine, which resulted in a transient remission, and a second‐line therapy with ibrutinib, which unfortunately failed to induce remission. We started a treatment with single‐agent obinutuzumab at a dose of 20 mg on day 1, 50 mg on day 2‐4, 330 mg on day 5, and 1000 mg on day 6. The laboratory analysis showed a rapid decrease of leukocyte count. Four weeks later, we repeated the treatment with obinutuzumab at a dose of 1000 mg q4w and started a therapy with venetoclax at a dose of 400 mg qd, which could be increased to 800 mg qd from the third cycle. This combination therapy was well tolerated. The patient achieved a complete remission (CR) after three cycles of obinutuzumab and venetoclax. To date, the patient has a progression‐free survival of 17 months under ongoing obinutuzumab maintenance q4w. This is the first report about obinutuzumab and venetoclax induced CR in rituximab‐intolerant patient with an ibrutinib‐resistant MCL. This case suggests that obinutuzumab‐ and venetoclax‐based combination therapy might be salvage therapy in patients with ibrutinib‐resistant MCL.

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Venetoclax: A new wave in hematooncology

Cited by 81 publications

References 127 publications

How I treat newly diagnosed acute myeloid leukemia in an outpatient setting: a multidisciplinary team perspective

How I treat newly diagnosed acute myeloid leukemia in an outpatient setting: a multidisciplinary team perspective

Comparison of putative BH3 mimetics AT-101, HA14-1, sabutoclax and TW-37 with ABT-737 in platelets

Obinutuzumab and venetoclax induced complete remission in a patient with ibrutinib‐resistant non‐nodal leukemic mantle cell lymphoma

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