Table 1:

Selected Sequencing Studies of Ibrutinib-Resistant CLL Patient Populations - Simple CLL Progression Only

		Number (%) of Patients with Indicated Mutations				Number of Ibrutinib-Resistant Patients with summed BTK/PLCG2 VAFs of:2
Study	Number of Patients1	BTK only	PLCG2 only	BTK and PLCG2	No identified BTK or PLCG2 mutation	<10%	10–30%	>30%
Maddocks [6]3	11	7 (64%)	2 (18%)	2 (18%)	0 (0%)	2 (18%)	2 (18%)	7 (64%)
Woyach [5]3	35	25 (71%)	1 (3%)	3 (8.6%)	6 (17%)	5 (17%)	7 (24%)	17 (59%)
Ahn [10]4	10	2 (20%)	1 (10%)	5 (50%)	2 (20%)	3 (43%)	0 (0%)	4 (57%)
Kadri [11]	3	1 (33%)	0 (0%)	0 (0%)	2 (67%)	0 (0%)	0 (0%)	1 (100%)5
Burger [18]	5	1 (20%)	1 (20%)	0 (0%)	3 (60%)	Not reported
Totals	64	36 (56%)	5 (7.8%)	10 (16%)	13 (20%)	10 (21%)	9 (19%)	29 60%)

¹Number of patients reflects only those patients in the studies that had CLL simple progression and next generation sequencing of the BTK and PLCG2 loci.

²Only patients that had detectable BTK and/or PLCG2 mutations are included in the percentage calculations.

³Eleven patients in the Maddocks cohort are also in the Woyach cohort. These eleven patients have been removed from the statistics reported for the Woyach cohort to avoid double counting.

⁴One subject with BTK and PLCG2 mutations did not have VAF testing; the denominator for VAF of the various frequencies is seven patients.

⁵Cancer cell fraction, and not variant allele frequency, was reported.