Authors: Mazyar Shadman, Bhavini P. Srivastava, Monika Salkar, Chadi Saifan, Barnabie C. Agatep, Barton Jones, Olga Ryan, Shaffee Bacchus, Deborah M. Stephens
Published: 2024-06-10
DOI: 10.1200/jco.2024.42.16_suppl.e19017
Source: Full article
e19017 Background: Dose reduction (DR) has been used to manage treatment-related adverse events (AEs) effectively and avoid early treatment discontinuation in patients (pts) with CLL/SLL receiving ibrutinib (ibr) in the first-line (1L) setting. This study evaluated DR and time to next treatment (TTNT) following AE in Medicare pts with CLL/SLL who were initiating ibr. Methods: Medicare Fee-for-Service (FFS) closed claims and enrollment data were used to identify pts with CLL/SLL who initiated 1L single-agent ibr (420 mg/day) from January 2014 to September 2020 with an incident AE following treatment initiation. Ibr DR was defined as reduction of starting dose following the first reported incident AE. Demographics, clinical characteristics, time to first incident AE, TTNT, and Healthcare Resource Utilization (HCRU) were analyzed among pts with and without DR (time to event measured in months). TTNT was defined as time from first incident AE to initiation of a new agent (≤90 days of ibr discontinuation) or death and was compared in pts with and without DR using Kaplan-Meier analysis and a time-varying Cox proportional hazards model. Results: Of 3575 pts included in the analysis (median age: 76 years; male: 63.4%), 459 (12.8%) had a DR. Duration of 1L ibr, time to first incident AE, time to DR, and TTNT varied among study cohorts. Median TTNT (standard deviation [SD]) for pts with and without DR was 49.8 months (1.4) and 22.0 months (0.6), respectively. After 6 and 12 months of follow-up, significantly fewer pts with DR discontinued treatment than pts without DR (6 months: 8.3% vs 27.3%, P = 0.0062; 12 months: 13.8% vs 38.2%, P = 0.0003). A total of 51 pts discontinued treatment immediately after the first incident AE; 414 deaths were reported within 90 days of the first incident AE. After controlling for baseline demographics and clinical characteristics as well as time-varying HCRU and costs, pts with DR were not significantly likely to discontinue treatment compared with pts without DR (hazard ratio [95% CI], DR vs no DR: 0.89 [0.71–1.12]). Increased age, comorbidity index score, healthcare costs, and number of hospitalizations were significant predictors of treatment discontinuation. Conclusions: Among Medicare FFS pts with CLL/SLL and an AE following initiation of 1L ibr, pts with DR remained on therapy significantly longer than pts without DR. Ibr DR may be an effective strategy to manage tolerability while maintaining clinical efficacy.