Contributions
Abstract: PB1919
Type: Publication Only
Background
Deeper insight is needed into the safety of tyrosine kinase inhibitors (TKIs) in chronic-phase chronic myeloid leukemia (CP-CML) outside clinical trials. SIMPLICITY (NCT01244750) is an ongoing observational study of CP-CML patients (pts) in routine clinical practice receiving first-line (1L) imatinib (IM), dasatinib (DAS) or nilotinib (NIL) in the US and Europe.
Aims
This analysis describes intolerances and reasons for hospitalizations (collectively defined as ‘events’) in the retrospective/prospective SIMPLICITY cohorts, in pts with 1, 3 and 5 years (yrs) of follow-up (FU) after start of 1L TKI.
Methods
Events collected consisted of intolerances on TKI change (dose change, discontinuation, or switching) and reported hospitalizations and associated reason. Demographics are given for pts with ≥1 event, and those with no events, by 5 yrs. Mean (±SD) number (no.) of events during 1, 3 and 5 yrs of FU are presented for the overall population, by 1L TKI, and in pts remaining on 1L TKI vs. those switching in the FU period. Pts discontinuing 1L TKI without switching to 2L TKI were excluded from the analysis. Common adverse events (AEs; all grades) are given by system organ class (SOC) for the overall population and will be given for the specified sub-cohorts.
Results
By September 07 2017, 1492 pts were enrolled in SIMPLICITY, of which 454, 666 and 720 pts had ≥1 events by 1, 3 and 5 yrs (of which 446, 586 and 357 pts had ≥1, 3 and 5 yrs of FU), and 990, 736 and 637 pts had no events (of which 961, 627 and 293 pts had ≥1, 3 and 5 yrs of FU). The median (interquartile range [IQR]; min–max) age of pts was 61 (50–71; 19–95) yrs in pts with ≥1 event and 52 (43–64; 18–91) yrs in pts with no events by 5 yrs. Pts with ≥1 event by 5 yrs had a higher mean (±SD) no. of comorbidities (3.8 [±2.9] vs. 2.5 [±2.4]) than pts with no events (p<0.001). There was a mean (±SD) of 2.6 (±2.2) events in 454 pts with ≥1 event by 1 yr: 3.4 (±2.6) events for pts who switched vs. 2.1 (±1.7) events in pts remaining on 1L TKI. There were 3.3 (±3.2) events in 666 pts with ≥1 event by 3 yrs: 4.2 (±3.6) events for pts who switched vs. 2.3 (±2.4) events in pts remaining on 1L TKI. There were 3.7 (±3.8) events in 720 pts with ≥1 event by 5 yrs: 4.7 (±4.3) events for pts switching vs. 2.6 (±2.6) in pts remaining on 1L TKI. There were differences between cohorts, with pts receiving 1L NIL having the highest no. of events at 1, 3 and 5 yrs (3.0, 3.9 and 4.1 vs. 2.3, 3.0 and 3.4 for DAS [p=0.02, p=0.009, p=0.08], 2.5, 3.2 and 3.7 [p=0.06 p=0.04, p=0.29] for prospective IM, and 2.8, 3.2 and 3.7 [ns] for retrospective IM). Across TKIs, common AEs by SOC were gastrointestinal disorders (27.8%, 29.4% and 31.5% by 1, 3 and 5 yrs), blood/lymphatic disorders (24.0%, 19.8%, and 19.4% by 1, 3 and 5 yrs), respiratory disorders (15.9%, 20.7% and 24.2% by 1, 3 and 5 yrs), and skin/subcutaneous disorders (14.5% and 14.1% by 1 and 3 yrs). No. and reasons for death will be presented.
Conclusion
Events were more frequent in pts switching vs. those remaining on 1L TKI, and inter-cohort comparisons showed the no. of events to be highest in 1L NIL pts at all time points. The no. of pts with events increased with longer FU. Common AEs are similar to those reported for TKIs in pivotal trials. SIMPLICITY is not designed to comprehensively capture these events, and thus presented data may offer a snapshot of TKI profiles. Our findings suggest, in routine clinical practice, events accrue with time, are associated with TKI switch, and vary by TKI; further analysis is ongoing.
Session topic: 8. Chronic myeloid leukemia - Clinical
Keyword(s): Adverse reaction, Chronic myeloid leukemia, Tyrosine kinase inhibitor
Abstract: PB1919
Type: Publication Only
Background
Deeper insight is needed into the safety of tyrosine kinase inhibitors (TKIs) in chronic-phase chronic myeloid leukemia (CP-CML) outside clinical trials. SIMPLICITY (NCT01244750) is an ongoing observational study of CP-CML patients (pts) in routine clinical practice receiving first-line (1L) imatinib (IM), dasatinib (DAS) or nilotinib (NIL) in the US and Europe.
Aims
This analysis describes intolerances and reasons for hospitalizations (collectively defined as ‘events’) in the retrospective/prospective SIMPLICITY cohorts, in pts with 1, 3 and 5 years (yrs) of follow-up (FU) after start of 1L TKI.
Methods
Events collected consisted of intolerances on TKI change (dose change, discontinuation, or switching) and reported hospitalizations and associated reason. Demographics are given for pts with ≥1 event, and those with no events, by 5 yrs. Mean (±SD) number (no.) of events during 1, 3 and 5 yrs of FU are presented for the overall population, by 1L TKI, and in pts remaining on 1L TKI vs. those switching in the FU period. Pts discontinuing 1L TKI without switching to 2L TKI were excluded from the analysis. Common adverse events (AEs; all grades) are given by system organ class (SOC) for the overall population and will be given for the specified sub-cohorts.
Results
By September 07 2017, 1492 pts were enrolled in SIMPLICITY, of which 454, 666 and 720 pts had ≥1 events by 1, 3 and 5 yrs (of which 446, 586 and 357 pts had ≥1, 3 and 5 yrs of FU), and 990, 736 and 637 pts had no events (of which 961, 627 and 293 pts had ≥1, 3 and 5 yrs of FU). The median (interquartile range [IQR]; min–max) age of pts was 61 (50–71; 19–95) yrs in pts with ≥1 event and 52 (43–64; 18–91) yrs in pts with no events by 5 yrs. Pts with ≥1 event by 5 yrs had a higher mean (±SD) no. of comorbidities (3.8 [±2.9] vs. 2.5 [±2.4]) than pts with no events (p<0.001). There was a mean (±SD) of 2.6 (±2.2) events in 454 pts with ≥1 event by 1 yr: 3.4 (±2.6) events for pts who switched vs. 2.1 (±1.7) events in pts remaining on 1L TKI. There were 3.3 (±3.2) events in 666 pts with ≥1 event by 3 yrs: 4.2 (±3.6) events for pts who switched vs. 2.3 (±2.4) events in pts remaining on 1L TKI. There were 3.7 (±3.8) events in 720 pts with ≥1 event by 5 yrs: 4.7 (±4.3) events for pts switching vs. 2.6 (±2.6) in pts remaining on 1L TKI. There were differences between cohorts, with pts receiving 1L NIL having the highest no. of events at 1, 3 and 5 yrs (3.0, 3.9 and 4.1 vs. 2.3, 3.0 and 3.4 for DAS [p=0.02, p=0.009, p=0.08], 2.5, 3.2 and 3.7 [p=0.06 p=0.04, p=0.29] for prospective IM, and 2.8, 3.2 and 3.7 [ns] for retrospective IM). Across TKIs, common AEs by SOC were gastrointestinal disorders (27.8%, 29.4% and 31.5% by 1, 3 and 5 yrs), blood/lymphatic disorders (24.0%, 19.8%, and 19.4% by 1, 3 and 5 yrs), respiratory disorders (15.9%, 20.7% and 24.2% by 1, 3 and 5 yrs), and skin/subcutaneous disorders (14.5% and 14.1% by 1 and 3 yrs). No. and reasons for death will be presented.
Conclusion
Events were more frequent in pts switching vs. those remaining on 1L TKI, and inter-cohort comparisons showed the no. of events to be highest in 1L NIL pts at all time points. The no. of pts with events increased with longer FU. Common AEs are similar to those reported for TKIs in pivotal trials. SIMPLICITY is not designed to comprehensively capture these events, and thus presented data may offer a snapshot of TKI profiles. Our findings suggest, in routine clinical practice, events accrue with time, are associated with TKI switch, and vary by TKI; further analysis is ongoing.
Session topic: 8. Chronic myeloid leukemia - Clinical
Keyword(s): Adverse reaction, Chronic myeloid leukemia, Tyrosine kinase inhibitor