Ibrutinib-Based Therapy in the Treatment of Relapsed and Refractory Chronic Lymphocytic Leukemia

Introduction. The development of Bruton's tyrosine kinase inhibitors and their introduction into clinical practice represent a major advance in the treatment of chronic lymphocytic leukemia (CLL). Several studies in CLL have determined the achievement of minimal residual disease (MRD) negativity as an independent favorable prognostic factor, associated with superior progression-free survival (PFS) and overall survival. MRD status is the single best posttreatment predictor of long-term outcomes after treatment, regardless of the treatment protocol or the presence of other pre-existing prognostic indicators.

Aim.To estimate of response rate, PFS and MRD after ibrutinib-based therapy in the treatment patients with relapsed/refractory CLL.

Methods.21 pts with relapsed/refractory CLL were included in the analysis. Stratification of patients into groups based on therapy. Group 1 (n = 14): 2nd and subsequent lines of rituximab-based chemotherapy (RB - 10, FCR - 4) and Group 2 (n = 12): ibrutinib-based therapy (420 mg daily oral Ibrutinib ± Chemoimmunotherapy). We have used NCI-IWCLL revised guidelines for treatment initiation and assessment of response. MRD was detected by multicolor flow cytometry of bone marrow in patients achieved a complete or partial remission: Group 1 - 7 pts, Group 2 - 5 pts.

Results. The median age was 60.5 years (45-83) in Group 1 and 62.5 years (49-82) in Group 2 and median previous lines of therapy was 1 (1-4) and 2 (1-4), respectively. Patients with unfavorable chromosomal abnormalities were detected in each group: Group 1 - 2 pts (combination del(11q) with del(13q)); Group 2 - 1 pts (del(17p)).

Overall response rate (ORR) in Group 1 was 71.4% (complete remission (CR) - 1 pt, partial remission (PR) - 9 pts, stable disease (SD) - 3 pts, progression disease - 1 pt). Group 2: ORR 91.7% (CR - 3 pts, PR - 8 pts; SD - 1 pt). Statistically significant differences in the frequency of ORR between groups were not detected (p>0.05).

MRD-negative remission rate was 40% (2/5, CR - 1 pt) in Group 2 compared to 14.3% (1/7 pts, CR) in Group 1 (p>0.05). Statistically significant differences in PFS were detected between Group 1 vs. Group 2 (p=0.0006). Median PFS in Group 2 has not been reached. Median PFS in Group 1 was 16.9 month.

Conclusion. Ibrutinib is highly effective at controlling disease, but best responses are typically partial remission, and patients must remain on treatment to maintain disease control. Evaluation of response and MRD after ibrutinib-containing therapy in the treatment of patients with relapsed/refractory chronic lymphocytic leukemia require further research.