Unit:
Κατεύθυνση Κλινικές Μελέτες: Σχεδιασμός και ΕκτέλεσηLibrary of the School of Health Sciences
Author:
Machairas Alexandros
Supervisors info:
Αγγελοπούλου Μαρία, Καθηγήτρια, Ιατρική σχολή, ΕΚΠΑ
Βασιλακόπουλος Θεόδωρος, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Σιακαντάρη Μαρίνα, Καθηγήτρια, Ιατρική σχολή, ΕΚΠΑ
Original Title:
Βιβλιογραφική ενημέρωση: θεραπεία με venetoclax στη χρόνια λεμφοκυτταρική λευχαιμία – ανάλυση προγνωστικών και προβλεπτικών παραγόντων
Translated title:
Prognostic and predictive factor analysis under venetoclax treatment in chronic lymphocytic leukemia: a review
Summary:
Introduction: Chronic lymphocytic leukemia is the most common adult leukemia in the Western world. New treatment options have significantly improved the overall survival of patients resulting in some of the prognostic and predictive factors established with chemoimmunotherapy losing their importance. This review addresses how these factors are affected under the widespread use of venetoclax therapy in CLL.
Methods: All clinical trials of venetoclax phase I, II, III in patients with CLL were reviewed after searching electronic databases. The results were evaluated in terms of PFS, OS, MRD, while to establish the independent prognostic significance of the variables, the data from the multivariate analysis for the prognostic/predictive factors were evaluated.
Results: With venetoclax-based therapy, 17p deletion, but not TP53 mutations, is still an independent adverse prognostic factor especially in relapsed/refractory (R/R) CLL, where only 27.3% remain progression free at 5 years. Unmutated IGHV status remains an independent prognostic factor according to trials, since it was associated with shorter progression free survival (PFS) under venetoclax. Complex karyotype, 11q deletion, NOTCH1 and BIRC3 mutations appear not to be associated with worse PFS under venetoclax. The high complex karyotype emerged as an independent adverse prognostic factor, as did translocations, lymph node enlargement > 5 cm and elevated β2 microglobulin (> 3.5 mg/l). SF3B1 mutation is a negative prognostic factor under venetoclax in R/R CLL but not in first line therapy. Finally, when venetoclax combined with anti-CD20, MRD remains indicative of survival (independent prognostic and predictive factor), whereas the data from the combination with BTK inhibitor show that its prognostic value is abolished in mutated IGHV, but it is preserved in unmutated IGHV patients.
Conclusions: Despite the encouraging results of better survival under venetoclax in patients with previously unfavorable prognostic factors, there is still a significant need to improve the outcome of patients with 17p deletion and unmutated IGHV status.
Main subject category:
Health Sciences
Keywords:
Chronic lymphocytic leukemia, Venetoclax, Treatment, Prognostic factors, Predictive factors
Number of references:
113
File:
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ΜΔΕ.pdf
6 MB
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