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A.R. Mato et al.
50%) or disease progression (19.6% versus 21.4%). Reasons for ibrutinib discontinuation are listed in Table 2. Percentages listed indicate the proportion of discontin- uations due to each category. Toxicity was the most com- mon reason for discontinuation in all settings, accounting for 63.1% of discontinuations in front-line use (n=12/80 front-line patients) and 50.2% of discontinuations in relapsed/refractory use (n=116/536 relapsed/refractory patients). Toxicity was the most common reason for dis- continuation in several settings including: commercial use and clinical trial use (50% of discontinuations in front-line commercial use, 77.7% of discontinuations in front-line clinical trial use, 52.5% of discontinuations in relapsed/refractory commercial use, and 39.7% of discon- tinuations in relapsed/refractory trial use). Notably, the proportion of discontinuations due to progressive disease was lower: 15.8% in the front-line setting and 20.9% in relapsed/refractory use. Richter transformation to diffuse large B-cell lymphoma or Hodgkin lymphoma accounted
Table 1. Baseline characteristics.
Total number
Median age at diagnosis, years (range)
Median time from diagnosis to ibrutinib start, months (range) del17p(+)
del11q(+)
Tp53mut(+)
Complex karyotype (+) (>3)
Median time diagnosis to ibrutinib, months (range)
Median ibrutinib starting dose
Ibrutinib administered as monotherapy
Ibrutinib suspension required
Ibrutinib dose adjusted
Median follow-up
for 5.3% of the discontinuations in the front-line setting and 5.0% in the relapsed/refractory setting.
Among the patients treated front-line with ibrutinib, the three most common toxicities leading to discontinuation were arthralgia (41.6%), atrial fibrillation (25%), and rash (16.7%). In the relapsed/refractory population, the most common toxicities leading to discontinuation were atrial fibrillation (12.3%), infection (10.7%), pneumonitis (9.9%), bleeding (9%) and diarrhea (6.6%).
The median time to ibrutinib discontinuation varied by toxicity: bleeding (8 months), diarrhea (7.5 months), atrial fibrillation (7 months), infection (6 months), arthralgia (5 months), pneumonitis (4.5 months) and rash (3.5 months).
Outcomes
At a median follow-up of 17 months, the median pro- gression-free and overall survival for the entire cohort were 35 months and not reached, respectively (Figure 1A,B). Overall survival from the start of ibrutinib therapy,
Baseline characteristics
Ibrutinib in front line
80
62 (37-88), n=78 25.5 (1-232), n=80 37%, n=76 19%, n=75 12%, n=42 40%, n=60
26 (1-232) 420 mg
68%, n=80 30%, n=79 15%, n=79
17 months
Ibrutinib in relapse
536
60 (22-95), n=532 78.3 (1-366), n=536 26%, n=368 35%, n=367 13%, n=142 34%, n=214
78 (1-660)
420 mg
89%, n=536 37%, n=310 20%, n=309
876
del17p(+) (deletion 17p mutation positive); del11q(+) (deletion 11q mutation positive); Tp53mut(+) (Tp53 mutation positive); Complex karyotype (+)(>3) (complex karyotype positive defined as three or more abnormalities).
AB
Figure 1. Outcomes for the entire cohort. Kaplan Meier curves at a median follow-up of 17 months showing (A) progression-free survival (PFS) for the entire cohort and (B) overall survival (OS) for the entire cohort.
haematologica | 2018; 103(5)