Open AccessPB1910 ANALYSIS OF CLL PATIENTS TREATED WITH BCR AND BCL‐2 INHIBITORS AND RICHTER TRANSFORMATION
Author(s) -
Naya D.,
Bravo J.,
NovaGurumeta S.,
FernándezCuevas B.,
PérezSanz N.,
Espinosa L.,
AlarcónTomás A.,
RomeraMartínez I.,
Montes A.,
Maestro A.,
GarcíaMarco J.A.
Publication year - 2019
Publication title -
hemasphere
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.677
H-Index - 11
ISSN - 2572-9241
DOI - 10.1097/01.hs9.0000566144.00043.5c
Subject(s) - ibrutinib , venetoclax , ighv@ , prolymphocytic leukemia , oncology , medicine , idelalisib , chronic lymphocytic leukemia , cytogenetics , breakpoint cluster region , cancer research , bruton's tyrosine kinase , leukemia , tyrosine kinase , biology , genetics , receptor , chromosome , gene
Background: BCR inhibitors such as Ibrutinib and idelalisib, as well as BCL‐2 inhibitors (Venetoclax) have been a revolution in CLL treatment in the last decade. Despite the good results with new drugs, around 15% of patients treated with Ibrutinib develop disease progression within 34 months and between 30 to 50% of those patients develop Richter Transformation (RT). Furthermore, it is also known that the prognosis of CLL is determined by cytogenetics and molecular factors. TP53 mutation, unmutated IGHV status, NOTCH1 mutation, SF3B1 mutation, 17p13 del, 11q22 del and Complex Karyotype are the main poor prognosis biomarkers in CLL. Aims: Our goal is to study the risk factors of Richter transformation (RT) in patients with CLL treated with BCR and BCL‐2 Inhibitors. Methods: We retrospectively reviewed data from 48 patient treated with BCR and BCL‐2 inhibitors. We classified them in two groups based on whether they had a Richter (or prolymphocytic) transformation or not. We select 12 cytogenetics and molecular variables (including Complex Karyotype, p53 mutation and IGHV mutational status). Results: In our cohort 3 out of 48 patients were treated with venetoclax (6.25%). 39 (81.25%) with Ibrutinib and other Bruton tyrosine kinase inhibitors (iBTKs), and 6 were treated with Idealisib (12.5%). 19 patients (39.5%) had a p53 disruption (TP53mut/del17p). Of the whole cohort, 9 patients (18.75%) developed a Richter or prolymphocytic transformation. Analysis of cytogenetics and molecular biomarkers demonstrated that only the presence of a p53 disruption was significantly associated with RT (p < 0.007). We analysed the molecular (NOTCH1, BIRC3, SF3B1, IGHV mutational status) and cytogenetics (Karyotype, del6q del11q, del13q, c‐myc, +12), only in patients with p53 disruption, and there was no significant association of complex karyotype with RT. We did find significant differences depending on whether they received idelalisib or ibrutinib. Patients treated with idelalisib had a higher rate of RT than those with ibrutinib, (p 0.001). We found the same results in the p53 disrupted cohort (p 0.013). Regarding the number of previous treatments before the BCR or BCL‐2, it was statistically significant that previously untreated patients had a lower risk of RT than patients treated in second or further lines of treatment (p value < 0.023). This was not significant in patients with p53 disruption. Patients with RT had a higher number of previous treatments (2.1), compared with patients without RT (0.6). The difference was also significant (p 0.013) in our main cohort, but we did not found significant differences in the p53 disrupted population. Summary/Conclusion: In our cohort, p53 disruption has the main biological impact in the RT, as it is described in several studies. We observed also that patient treated with chemoimmunotherapy before BCR or BCL‐2 inhibitor had a higher risk of RT than naïve patients as it is described in recent publications. We also found that patients treated with idelalisib had an increased risk of RT compared to those patients treated with BCR inhibitors.