Treatment Discontinuation Patterns for Patients with CLL in the Real-World Settings: Results from a Multi-Center Study

• Published in: Blood 2019-11, Vol.134 (Supplement_1), p.3048-3048
• Main Authors: Shadman, Mazyar, Sail, Kavita, Manzoor, Beenish S, Yazdy, Maryam Sarraf, Hill, Brian T., Tuncer, Hande H., Allan, John N., Ujjani, Chaitra S., Emechebe, Nnadozie, Kamalakar, Rajesh, Sharmokh, Simon, Jiang, Daniel Dingfeng, Pena, German, Marshall, Thomas, Nielsen, Jacqueline, Barr, Paul M., Brown, Jennifer R., Schuh, Anna, Eyre, Toby A., Lamanna, Nicole, Wierda, William G., Skarbnik, Alan, Roeker, Lindsey E., Bannerji, Rajat, Pauff, James M., Schuster, Stephen J., Follows, George A, Cheson, Bruce D., Eichhorst, Barbara F., Brander, Danielle M., Pivneva, Irina, Guerin, Annie, Mato, Anthony R.
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2019-131401

BACKGROUND The recent approval of novel agents (NAs) has changed the treatment landscape in chronic lymphocytic leukemia (CLL), however, there remains uncertainty regarding treatment discontinuation patterns in real-world (RW) settings. This study assessed patterns of and reasons for discontinuation for patients (pts) treated with chemotherapy/chemoimmunotherapy (CT/CIT) and NAs in first (1L) and second (2L) lines of therapy in CLL. METHODS The CLL Collaborative Study of Real-World Evidence (CORE) study is a retrospective, multicenter, observational study. Adult CLL patients (pts) were included if they were diagnosed with CLL, initiated 1L or 2L therapy for CLL on/after 01/01/2012 (excluding lines of therapy received as part of clinical trials). Discontinuation patterns were assessed among CT/CIT and NAs, more specifically in four treatment cohorts: fludarabine+cyclophosphamide+rituximab (FCR), bendamustine+rituximab (BR), B-cell receptor inhibitors (BCRi)-based (e.g., acalabrutinib, ibrutinib, or idelalisib) and venetoclax-based regimens. Treatment discontinuation was operationally defined as ending therapy for reason(s) other than completion of planned duration of therapy. RESULTS Of 671 pts receiving 1L therapy, 81 (12%) received FCR (median age=58, 70% males); 153 (23%) BR (median age=63, 61% males), 255 (38%) BCRi-based (median age=65, 65% males); and 13 (2%) venetoclax-based (median age=59, 54% males). The remaining 169 pts received other regimens (e.g., other CT/CIT). The most common BCRi-based therapy in 1L was ibrutinib-containing regimens (97%). Median duration of follow-up was 24, 27, 11 and 8 months for FCR, BR, BCRi-based and venetoclax-based regimens, respectively. Treatment discontinuation occurred in 18 (22%), 41 (27%), 51 (20%) and 4/13 pts receiving FCR, BR, BCRi-based and venetoclax-based regimens, respectively. The most common reason for discontinuation in FCR (11/18 pts; 61%), BR (15/41 pts; 37%) and BCRi-based (24/51 pts; 47%) cohorts was adverse events (AEs), with >70% being severe AEs in each cohort. Common AEs leading to discontinuations were hematological abnormalities (e.g., neutropenia, thrombocytopenia) in the FCR (6/18 pts; 33%) and BR (6/41 pts; 15%) cohorts. In the BCRi-based cohort the most common AEs leading to discontinuations were cardiac (4/51 pts; 8%), skin and subcutaneous tissue disorders (e.g., rash; 6/51 pts; 12%), hemorrhage/bleeding (3/51; 6%), and musculoskeletal and connective tissue disorders (3/51; pts; 6%).