Unit:
Faculty of MedicineLibrary of the School of Health Sciences
Author:
Gkioka Annita-Ioanna
Dissertation committee:
Κυρτσώνη Μαρία-Χριστίνα, Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Παναγιωτίδης Παναγιώτης, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Βασιλακόπουλος Θεόδωρος, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Καθηγητής Δεδούσης Γεώργιος, Καθηγητής, Τμήμα Επιστήμης Διαιτολογίας – Διατροφής, Χαροκόπειο Πανεπιστήμιο
Κοντοπίδου Φλώρα, Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Τέρπος Ευάγγελος, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Τσιριγώτης Παναγιώτης, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Original Title:
Κλινικοί και βιολογικοί προγνωστικοί παράγοντες ανταπόκρισης στη θεραπεία στο Πολλαπλούν Mυέλωμα
Translated title:
Clinical and biological prognostic factors of treatment response in Multiple Myeloma
Summary:
Despite the significant progress in treatment options in Multiple Myeloma (MM), the prognosis is still poor for patients with special characteristics, not accounted for in existing risk stratification models. The purpose of the present study was to evaluate the efficacy of novel treatments in MM in a real word setting cohort and to investigate the possible prognostic value of biologic factors in this novel era. For this purpose, four hundred and thirty-eight (N=438) MM patients were recorded and studied in terms of clinical and laboratory characteristics as well as the number of treatment line registration. The study was focused on resistance to lenalidomide treatment therapy in MM. Relapse to lenalidomide revealed 5 distinct groups of patients, according to time to relapse that were associated to overall survival after Lenalidomide (LenOS). Relapse after 5 years of Lenalidomide-Dexamethasone (LD) was associated with the best overall survival following LD.
Cereblon (CRBN), as a target protein of IMiDs, was measured in the serum of 92 patients treated with Lenalidomide. Lenalidomide relapse was associated with elevated CRBN levels. Also, elevated levels relative to median in patients' serum were shown to be associated with early relapse in LD (≤ 12 months) (p=0.03) and lower than median levels with seven-year overall LenOS (p =0.013).
miRNAs, or small non-coding RNA molecules, are another emerging key component that has shown potential predictive efficacy in MM. miR-16 and miR-21 levels were measured in the serum of 48 patients with PM at diagnosis and in 35 patients with relapsed/refractory MM before LD treatment and in 15 healthy individuals. Serum miR-16 and miR-21 expression was significantly decreased in patients with MM serum at diagnosis compared to HI (median miR-16 0.047 vs 1.89 and median miR-21 0.051 vs 1.59, p< 0.001). Improved overall survival was observed in patients with lower miR-16 levels (p=0.024). Serum miR-21 levels correlated with ISS (r=0.468, p=0.018) and treatment response (≥VgPR) (r=0.453, p=0.034). Two fold expression of serum miR-16 levels (x2) above the median value in relapsed/refractory MM patients was associated with treatment response (≥PR) (r=0.427, p=0.05). miR-16 LD/DX ratio above 2 (≥2) was significantly associated with time to response (p=0.027), while miR-21 LD/DX ratio above 2 (≥2) was associated with time to next treatment ( p=0.042). Distant relapse in LD after 24 months was significantly associated with both miR-16 LD/DX ratio (p=0.001) and miR-21 LD/DX ratio (p=0.038).
In summary, in this thesis, real-world data from the treatment lines of 438 MM patients were demonstrated with a particular focus on Lenalidomide refractoriness. Serum levels of CRBN were measured in MM patients treated with lenalidomide and their prognostic significance in these patients was demonstrated. Rising prognostic factors are miR- 16 and miR-21 in MM as demonstrated by this study with significant prognostic significance for the overall survival of patients as well as their response to IMiDs
Main subject category:
Health Sciences
Keywords:
Multiple Myeloma, Prognostic Factors, Cereblon (CRBN), miRNAs, Lenalidomide refractoriness
Number of references:
171
