PB1911 THE CLINICAL EFFICACY OF IBRUTINIB IN RELAPSED AND RESISTANT CHRONIC LYMPHOCYTIC LEUKEMIA PATIENTS
Authors: Kataeva E. , Golenkov A. , Klinushkina E. , Zakharov S. , Trifonova E. , Chernykh Y. , Vusotskaya L. , Belousov K. , Mitina T. , Chuksina Y. , Kogarko I. 
Published: June 2019

Background:

Chronic lymphocytic leukemia (CLL) is characterized by its recurrent nature and its developing resistance to standard methods of treatment. This is especially relevant for the 17p‐ deletion patients with unfavorable prognosis. In this regard, the study of the clinical efficacy of the Bruton's tirosine kinase inhibitor, Ibrutinib, in relapsed and resistant CLL patients in real clinical practice is of great importance.

Aims:

to study the clinical efficacy of Ibrutinib in CLL patients relapced/resistant (R/R) to the preceding therapy, in real clinical practice.

Methods:

35 CLL patients with stage II‐IV according to Rai, aged 29 to 71 (Me, 58), 12 female, 23 male, were included into the research. 8 patients were experiencing their first early relapse, which had developed in less than 24 months after their remission. 27 patients proved to be resistant to the preceding therapy. 17p13/TP53 deletion was studied in 32 patients in accordance with the FISH method, prior to Ibrutinib treatment. Ibrutinib was prescribed daily in the dosage of 420 mg. The patients were thoroughly observed every three months. The assessment of the clinical efficacy was done according to the criteria of the International Workshop on Chronic Lymhocytic Leukemia (IWCLL, 2008). The statistical analysis was carried out in accordance with the Student's t‐test.

Results:

All the patients had been pre‐treated in Me 48 months (4‐129). The Me number of lines of polychemotherapy constituted 3 (1‐4). The number of cycles of the preceding RFC ‐therapy (Rituximab, Fludarabine, Cyclophosphamide) ranged from 1 to 11, Me 6; R‐CHOP‐therapy (Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, Prednisolone) ranged from 1 to 9, Me 6; RB‐therapy (Rituximab and Bendamustin) ranged from 2 to 9, Me 6. The patients were being observed for Me of 9 months (4‐40). Among the 35 patients who took part in the study, the overall response rate to the Ibrutinib treatment was observed in 100% of cases (n = 35). Among them, 9 complete remission (CR) (25,7%) and 26 partial remission (PR) (74,2%) were observed, as well. While analyzing the response to the Ibrutinib treatment of two patient groups – with 17p13/TP53 deletion (n = 14) and without deletion (n = 18), the following results were obtained. In the deletion group CR was observed in 3 (21,4%) and PR in 11 (78,5%). Whereas among the group without deletion CR was observed in 4 (22,2%), PR in 14 (77,7%) (p > 0,05).

While analyzing 9‐month survival rate, it was established that it had constituted 96,5%. Out of 35 patients, 7 died during the research. Their survival rate was 12 months.

It is noteworthy that some patients had serious infectious complications, such as pneumonia in 6 cases (17,1%), Guillain–Barré syndrome in 1 case (2,8%), Evans–Fisher syndrome in 1 case (2,8%), and it induced a serious diarrhea in case of one patient, which became the reason for lowering the dose

Summary/Conclusion:

The following results have shown great efficacy of Ibrutinib among pre‐treated CLL R/R patients. 17p13/TP53 deletion hasn’t influenced the clinical efficacy of Ibrutinib.