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P.M. Barr et al.
cephalopathy reported.
Serious AEs over the 3 years of follow up occurring in
more than 2 ibrutinib-treated patients included pneumo- nia (11; 8%), atrial fibrillation (6; 4%), urinary tract infec- tion (5; 4%), basal cell carcinoma (5; 4%), hyponatremia (5; 4%), pleural effusion (4; 3%), hypertension (3; 2%), and anemia (3; 2%).
Eighteen patients (13%) required dose reductions and 16 patients (12%) discontinued first-line ibrutinib because of AEs. AEs leading to discontinuation in more than 1 patient included infection (n=5), hemorrhage (n=3), atri- al fibrillation (n=2), and rash (n=2). Treatment-limiting toxicity including both reductions and discontinuations due to AEs decreased over time with ibrutinib (Figure 4).
Concomitant medications
Concomitant medications were collected throughout the duration of ibrutinib treatment (median, 28.5 months) and chlorambucil (median, 7.1 months). Despite longer
follow up recording of the use of these agents in the ibru- tinib arm versus the chlorambucil arm, the rate of neu- trophil growth factor use and platelet and red blood cell transfusion was higher in the chlorambucil arm. Intravenous immunoglobulin was administered to 4% of ibrutinib-treated patients versus 2% of those randomized to chlorambucil. Anticoagulants and/or antiplatelet agents were frequently used during study therapy (56% and 54% of patients treated with ibrutinib and chlorambucil, respectively; Online Supplementary Table S3), including anticoagulants in 21% of the ibrutinib-treated patients.
Outcomes following ibrutinib discontinuation
With up to 3 years follow up, out of 136 patients, only 4 patients discontinued ibrutinib primarily due to disease progression; 1 had unmutated IGHV and none were reported to have del(11q). Two of these 4 patients remain alive. Of the 16 patients who discontinued ibrutinib because of AEs; 13 (81%) are alive with a median of 13
Sex
Figure 2. PFS subgroup analysis.
Table 2. Response rates in ibrutinib-treated patients.
Best response, n (%)
ORR
CR/CRi
All patients (n=136)
125 (92)
25 (18)
With del(11q) (n=29)
29 (100)
4 (14)
Without del(11q) (n=101)
91 (90)
20 (20)
Mutated IGHV (n=40)
35 (88)
8 (20)
Unmutated IGHV (n=58)
55 (95)
12 (21)
nPR 1(1) 0 1(1) 3(8) 0
PR 97 (71) 25 (86) 68 (67) 26 (65) 43 (74)
PR-L 2(1) 0 2(2) 0 0
Cri: complete response with incomplete blood-count recovery; nPR: nodular partial response (defined according to the International Workshop on Chronic Lymphocytic Leukemia criteria for response16 as a complete response with lymphoid nodules in the bone marrow); PR: partial response; PR-L: partial response with lymphocytosis.
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haematologica | 2018; 103(9)