SUPPLEMENTARY APPENDIX
Supplement to Coutre SE, Furman RR, Flinn IW et al. Extended treatment with
single-agent ibrutinib at the 420 mg dose leads to durable responses in chronic
lymphocytic leukemia/small lymphocytic lymphoma
CONTENTS
Supplementary Table S1. Patient disposition
Supplementary Table S2. Summary of adverse events
Supplementary Table S3. Response improvement and durability
Supplementary Table S4. Best response in patients who achieved PR with
lymphocytosis
Supplementary Table S5. Outcomes by cytogenetics (FISH) in the
relapsed/refractory population
Supplementary Figure 1. Outcomes by cytogenetics (FISH) in the relapsed
refractory population. (A) Progression-free survival and (B) overall survival in
cytogenetic subgroups in patients with R/R CLL/SLL.
Supplementary Table 1.
TN ≥65 years
R/R
(n = 27), n (%)
(n = 67), n (%)
30.4 (1.3-44.2)
21.9 (0.3-44.6)
≤1 year
4 (15%)
13 (19%)
1-2 years
1 (4%)
26 (39%)
2-3 years
12 (44%)
22 (33%)
>3 years
10 (37%)
6 (9%)
22 (81%)
40 (60%)
Progressive disease
1 (4%)
11 (16%)
Adverse eventb
3 (11%)
9 (13%)
Consent withdrawal
1 (4%)
2 (3%)
Investigator’s decision
0%
4 (6%)
Other
0%
1 (1%)
All patients
Median time on treatmenta, months (range)
Duration of study treatment
Patients remaining on ibrutinib therapy
Primary reason for discontinuation
R/R, relapsed/refractory; TN, treatment-naïve.
a
Sixty-six percent of total patients remain on ibrutinib therapy.
b
Discontinuation due to adverse events occurred in 7 patients during year 1, 3 patients
during year 2, and 2 patients during year 3 and after.
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Supplementary Table 2.
TN ≥65 years
R/R
(n = 27), n (%)
(n = 67), n (%)
17 (63%)
55 (82%)
Any infections
3 (11%)
32 (48%)
Ibrutinib-relateda
6 (22%)
25 (37%)
Any
7 (26%)
46 (69%)
Ibrutinib-relateda
1 (4%)
8 (12%)
Dose reduction due to an adverse eventb
1 (4%)
7 (10%)
Death on study
1 (4%)
7 (10%)
All patients
Grade ≥3 adverse events
Any
Grade ≥3 serious adverse events
R/R, relapsed/refractory; TN, treatment-naïve.
a
Related to ibrutinib by investigator assessment.
b
Dose reduction due to adverse events occurred in 7 patients during year 1 and in 1 R/R
patient during year 3.
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Supplementary Table 3.
All patients
Median time to Initial
TN ≥65 years
(n = 21)
R/R
(n = 61)
Total
(N = 82)
1.9 months
1.8 months
1.8 months
7.4 months
7.4 months
7.4 months
15.6 months
19.9 months
15.6 months
NR
NR
NR
95.2 (70.7 - 99.3)
79.1 (65.3 – 87.9)
83.8 (73.2 – 90.5)
response
Median time to best
response
Median time to CR
Median DOR, months
30-month DOR, % (95%CI)
CR, complete response; DOR, duration of response; NE, not estimable; NR, not reached, MTTR,
median time to response.
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Supplementary Table 4.
TN ≥65 years
(n = 27), n (%)
R/R
(n = 67), n (%)
Total
(N = 94), n (%)
Patients with PR-L, n
12
41
53
Achieved CR/PR
10 (83%)
39 (95%)
49 (92%)
All patients
CR
Not achieving CR/PR
3 (25%)
4 (10%)
7 (13%)
2 (17%)
2 (5%)
4 (8%)
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Supplementary Table 5.
R/R patients
30-month PFS, % (95% CI)
Median PFS, months
30-month OS, % (95% CI)
Median OS, months
Del17p
(n = 23)
Del11q
(n = 18)
No del17p/11q
(n = 23)
59.6 (34.4-77.9)
82.4 (54.7-93.9)
85.0 (60.2-94.9)
32.4
Not reached
Not reached
81.3 (57.6-92.6)
88.2 (60.6-96.9)
90.3 (66.3-97.5)
Not reached
Not reached
Not reached
FISH, fluorescent in situ hybridization; OS, overall survival; PFS, progression-free survival.
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Supplementary Figure 1.
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