SALT LAKE CITY — Novel oral agents (NOAs), such as acalabrutinib, duvelisib, ibrutinib, idelalisib and venetoclax are increasingly used instead of traditional chemoimmunotherapy for chronic lymphocytic leukemia, the most common leukemia in adults.
A presentation at the 61st American Society of Hematology Annual Meeting and Exposition in Orlando pointed out that, unlike chemotherapy, most NOAs are given daily for an indefinite period of time and are self-administered at home. While that raises concerns, researchers from the University of Utah and the George E. Wahlen Veterans Health Administration system, both in Salt Lake City, noted that discontinuation patterns of NOAs in a real-world population remained unknown.1
To remedy that, the study team used the VA Cancer Registry System and electronic healthcare records to identify patients treated for CLL with NOAs in the VA from Nov. 1, 2013, to Nov. 30, 2018. Researchers followed patients from the first NOA dispensation until death or the end of the study observation on May 31, 2019.
NOAs were selected in accordance with the National Comprehensive Cancer Network guidelines for CLL, and information on them was extracted using pharmacy dispensation records.
For purposes of the study, discontinuation was defined as the absence of NOA dispensation within 60 days of estimated exhaustion of patient’s NOA supply from the last recorded dispensation.
The study classified a discontinuation event for each NOA treatment episode in each patient as either 1) a drug holiday, if there was evidence of resumption of the same treatment without any other treatment interventions after the first discontinuation; or 2) permanent discontinuation, in which the treatment ceased without evidence of resumption for 60 days or there was evidence of new treatment initiation after the discontinuation of previous treatment.
Ultimately, 1,196 CLL patients treated with NOAs during the study period were identified. Participants had a mean age at NOA initiation of 70.7 years and 96.7% of patients were male. The report also noted that the median time from diagnosis to NOA initiation was 56.5 months (0-189.5 months).
In terms of therapy, of the 1,196 patients treated with NOAs, 1,172 received ibrutinib, 53 received idelalisib and 106 received venetoclax. There were 10 or fewer patients treated with acalabrutinib and duvelisib, so those patients were omitted from the final analyses.
Researchers pointed out that, during a median follow-up of 18.9 months, 48.2% NOA treatment courses were followed by a discontinuation event. The proportions of patients who discontinued for ibrutinib, idelalisib and venetoclax were 47.5%, 77.4%, and 41.5%, respectively.
At the end of the study observation, however, 52.6% of ibrutinib, 22.6% of idelalisib and 58.3% of venetoclax treatment courses were still being administered.
The presentation detailed the following:
- In first-line ibrutinib, the median NOA treatment duration until the first discontinuation was 10.7 months (0.8-55.8 months), 12.6 months (0.5-62.0 months) in second-line (L2) IBR, and 12.2 months (0.78-57.8 months) in third-line or subsequent lines.
- In idelalisib treatment courses, the median treatment duration until the first discontinuation was 17.8 months (1.9-41.6 months) in second-line and 4.3 months (1.7-26.2 months) in third-line or subsequent lines.
- In venetoclax treatment courses, the median time until the first discontinuation was 8.4 months (3.1-26.0 months) in second-line and 7.4 months (1.7-18.5 months) in third-line or subsequent lines.
At the same time, of 532 first-line ibrutinib treatment courses with more than one dispensation, 96 (18%) were associated with a drug holiday and 97 (18%) with permanent discontinuation. Comparable numbers were 64 (27%) and 50 (21%) for line two, and 90 (28%) and 76 (24%) for line three and subsequent courses.
In addition, 24 (67%) of line three idelalisib treatment courses with more than one dispensation were associated with permanent discontinuation, and, among 63 line three venetoclax courses with more than one dispensation, 6 (10%) were associated with a drug holiday and 14 (22%) with permanent discontinuation.
“To our knowledge, this study is the first to report on the NOA discontinuation in a nationwide VA cohort of CLL patients treated in a real-world setting,” the authors concluded. “Our results suggest there is a substantial proportion of drug holidays and permanent discontinuation among commonly used NOAs. Further efforts will focus on understanding factors leading to discontinuation and the impact of discontinuation/drug holidays on clinical outcomes.”
- Chien H-C, Vikas P, Rasmussen K, Young C. Discontinuation Patterns in Patients Receiving Novel Oral Agents for Chronic Lymphocytic Leukemia in the Veterans Health Administration. Presented at the 61st American Society of Hematology Annual Meeting and Exposition; December 2019; Orlando, FL