Zie ook literatuurlijst niet-toxische middelen en behandelingen specifiek bij vormen van leukemie van arts-bioloog drs. Engelbert Valstar

Zie ook dit artikel: https://kanker-actueel.nl/NL/venetoclax-een-kleine-molecuulremmer-uit-de-bcl-2-groep-geeft-veelbelovende-resultaten-bij-vergevorderde-zwaar-voorbehandelde-multiple-myeloma-kahler.html

1 juni 2022: Bron: The Lancet online Published:May 02, 2022 Per 1 juni 2022 in papieren versie

Uit een fase 2-studie uitgevoerd in drie openbare ziekenhuizen in China blijkt dat Venetoclax (merknaam Venclexta) aanvullend gegeven op een chemokuur met Daunorubicine en Cytarabine als eerstelijnsbehandeling voor volwassenen met AML - Acute Myeloide Leukemie bijzonder goede resultaten geeft op 1-jaars meting. 

Uit het abstract vertaald:

  • Een complete remissie na één cyclus van het DAV-regime was 91% (95% BI 76-98; 30 van 33 patiënten) gemeten over de hele studiegroep. 29 (97%) van de 30 patiënten die een volledige remissie bereikten, hadden een niet-detecteerbare, meetbare restziekte (dwz <0,1%).
  • Graad 3 of nog ernstigere bijwerkingen waren neutropenie bij 33 (100%) van de 33 patiënten, trombocytopenie bij 33 (100%), anemie - bloedarmoede bij 33 (100%), febriele neutropenie bij 18 (55%), pneumonie - longontsteking bij zeven (21%) , en sepsis in vier (12%).
  • Er deden zich geen aan de behandeling gerelateerde sterfgevallen voor.
  • Met een mediane follow-up van 11 maanden (IQR 9–12), was de geschatte totale overleving na 1 jaar 97% (95% BI 91–100) en was de 1 jaar ziektevrije overleving 72% (56–94).

Deze studie, gepubliceerd in The Lancet 2 mei 2022  bewijst volgens de onderzoekers dat venetoclax voor patiënten met acute myeloïde leukemie (AML) een nieuwe behandelingsoptie kan zijn. Ook kan venetoclax een belangrijke rol spelen bij het verbeteren van de werkzaamheid van intensieve chemotherapie bij daarvoor in aanmerking komende patiënten. 

Hier een grafiek over de bijwerkingen:



Hier het abstract zoals dat is gepubliceerd is in The Lancet. Voor het volledige studierapport moet worden betaald: 

ARTICLES| VOLUME 9, ISSUE 6E415-E424, JUNE 01, 2022

Venetoclax plus 3 + 7 daunorubicin and cytarabine chemotherapy as first-line treatment for adults with acute myeloid leukaemia: a multicentre, single-arm, phase 2 trial


Summary

Background

Adults with acute myeloid leukaemia have unsatisfactory clinical outcomes and rates of complete remission. Venetoclax combined with azacytidine or low-dose cytarabine has shown efficacy in adults aged 75 years or older (or 18–74 years with comorbidities precluding intensive chemotherapy) with acute myeloid leukaemia. We aimed to investigate the activity and safety of venetoclax plus 3+7 daunorubicin and cytarabine chemotherapy in adults with acute myeloid leukaemia.

Methods

We conducted a two-stage, single-arm, phase 2 trial at three public hospitals in China. We enrolled patients aged 18–60 years with previously untreated de novo acute myeloid leukaemia and an Eastern Cooperative Oncology Group performance status of 0–2. Patients received induction treatment with intravenous daunorubicin (60 mg/m2 on days 1–3), intravenous cytarabine (100 mg/m2 on days 1–7), and oral venetoclax (100 mg on day 4, 200 mg on day 5, and 400 mg on days 6–11; DAV regimen). For induction therapy, the length of the treatment was 28–35 days per cycle and the number of treatment cycles was one or two. The primary endpoint was the composite complete remission rate (complete remission plus complete remission with incomplete blood cell count recovery) after one cycle of induction treatment, assessed in the as-treated population. Secondary endpoints were bone marrow measurable residual disease by flow cytometry, event-free survival, overall survival, and adverse events. This trial is ongoing and is registered with Chinese Clinical Trial Registry, ChiCTR2000041509.

Findings

Between Dec 25, 2020, and July 7, 2021, 36 patients were assessed for eligibility and 33 were enrolled. 15 (45%) patients were men and 18 (55%) were women, and all were Asian. The composite complete remission rate after one cycle of DAV regimen was 91% (95% CI 76–98; 30 of 33 patients) in the entire cohort. 29 (97%) of 30 patients who reached complete remission had undetectable measurable residual disease (ie, <0·1%). Grade 3 or worse adverse events included neutropenia in 33 (100%) of 33 patients, thrombocytopenia in 33 (100%), anaemia in 33 (100%), febrile neutropenia in 18 (55%), pneumonia in seven (21%), and sepsis in four (12%). No treatment-related deaths occurred. With a median follow-up of 11 months (IQR 9–12), estimated 1-year overall survival was 97% (95% CI 91–100) and 1-year event-free survival was 72% (56–94).

Interpretation

The DAV regimen represents an effective induction therapy for newly diagnosed adults with acute myeloid leukaemia, which resulted in a high rate of complete remission. These findings are an important contribution to the field, showing a safe strategy to incorporate venetoclax into the most common induction regimen used to treat newly diagnosed acute myeloid leukaemia internationally.

Funding

Leading Innovative and Entrepreneur Team Introduction Program of Zhejiang, National Natural Science Foundation of China, Key Research and Development Program of Zhejiang.

Translation

For the Chinese translation of the abstract see Supplementary Materials section.

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