Impact on Quality of Life (QoL) of Patients with Chronic Lymphocytic Leukemia and Mantle Cell Lymphoma Under Ibrutinib Treatment: Preliminary Data from a Real World Prospective Project (pilot study)

Introduction

Ibrutinib (Ibr), is a first-in-class, orally administered covalent inhibitor of Bruton Tirosine Kinase (BTK). In Argentina, IMBRUVICA™ has recently been approved by ANMAT (Argentinian Regulatory Agency) as first or second-line treatment option for patients (pts) diagnosed with Chronic lymphocytic leukemia (CLL) and as second-line treatment for Mantle cell lymphoma (MCL), as well as CLL pts with a chromosomal deletion of 17p. As there is no available information on the impact of Ibr in QoL measurements in the real-world, outside of a sponsored clinical trial, no preliminary hypothesis can be drawn; but considering evidence from controlled trials it is likely that treatment with Ibr could result in an improvement in QoL. Taking this premise, we suggest a probable benefit on QoL in patients under Ibr of ≥ 20% during the first year of treatment compared to baseline.

Objectives

We aim to detect an improvement in QoL using patient-reported outcomes. Secondary Objective: To evaluate the effects of Ibr on QoL at different times of treatment. Assess hemoglobin variation during treatment with Ibr.

Materials and Methods

All pts signed informed consent (IC) to perform QoL questionnaires and use of personal data. This study is in accordance with the Helsinki declaration. Exploratory analyzes were performed on the evaluations of the results reported by the pt from the Euro-QOL5D questionnaire (EQ5D) with explicit permission to do so from the copyright holder. Both, the descriptive and visual analogue scale (VAS) were analyzed. This information was used as a quantitative measure of health, as judged by the respondents. EQ5D was completed by patients on months 0, 1, 3, 6 and 12 from the start of treatment. At the same time, doses of Ibr and hemoglobin (Hb) value were recorded.

Results

Twelve pts who started monotherapy with Ibr at our center between January 2016 and February 2017 were included. A total of 11 pts (92%) had a diagnosis of CLL and 1 pt (8%) of MCL. The majority of pts, 8 (67%) were men and median age was 75 years (51-84). The starting dose was 420 mg/d in all cases of CLL and 560 mg/d in MCL. Baseline Hb was 11.1 mg/dl (9.0-14.9). In 9 pts (75%) Ibr was a salvage regimen and in 3 pts (25%) was 1^st line therapy. Two pts who had signed IC died before completing QoL evaluation from not related to Ibr causes. The median time of treatment was 12 months (1-18). With the EQ5D VAS evaluation, 90% of the pts reported improvement in their perception of health after the initiation of treatment with Ibr, comparing baseline to 3 and 6 month assessments. None reported worsening of QoL. We observed a modification on the VAS EQ with median improvement of 29% (8-80%) after treatment initiation. Median Hb variation during treatment was: 11.1; 11.2; 11.6; 13 and 13.1mg/dl at 1, 3, 6 and 12 months of treatment, respectively. This means a median Hb improvement of 2gr/dl in the first year of treatment. Interestingly, 2 pts (25%) started treatment with normal values of Hb and also reported QoL improvement. Regarding the different areas of evaluation that comprise the EQ5D, improvements were mainly reported in pain, mobility, daily activities and anxiety.

Conclusions

In this prospective pilot study of QoL assessment with Ibr treatment, we observed that there was an improvement of 29% in this initial sample. This responds positively to the hypothesis raised of an improvement ≥ 20%. Even thought QoL improvement could be partially explained with Hb increase, the Ibr effect on QoL in pts with no baseline anemia is an interesting finding and remains to be determined. We expect to continue with the recruitment of patients by extending the proposal to other centers to reach the sample size needed for statistical confirmation.