Table 1.

Overview of selected studies describing the incidence of resistance-associated mutations in CLL patients treated with ibrutinib including selected studies describing resistance-associated mutations in patients with Richter transformation^#.

References	Number of patients	Genetic characteristics of patients	Number of previous treatment lines, median (min-max)	Frequency of patients with resistance-associated mutations	BTK mutation		PLCG2 mutation
					Variant(s)	VAF	Variant(s)	VAF
Woyach et al. (10)	6	3/6 del(17p) + CK 1/6 del(17p) + trisomy 12 1/6 CK 1/6 del(11q)	4 (2–9)	100% (6/6)	C481S	17–60%	R665W S707Y L845F	8–38%
Burger et al. (23)	5	4/5 del(17p) + del(13q) 1/5 del(11q)	4 (1–6)	40% (2/5)	C481S	NA	S707F D993H M1141K/R	12–35%
Sharma et al. (19)#	1*	1/1 del(17p)	1	100% (1/1)	T316A	75%	0	0
Ahn et al. (12)#	10	10/10 del(17p)/mutation TP53	NA	80% (8/10)	C481S/R	2–78%	P664S R665W S707Y L845F 6 nt del	0.1–18%
Woyach et al. (13)	54	40% del(17p)**58% CK	3 (0–16)	89% (48/54)	C481S/R/F	0.2–100%	R665W S707Y/P/F L845F D993Y L845-846del	4–44%
Kadri et al. (14)#	9***	8/9 del(17p)	2 (1–4)	56% (5/9)	C481S/R T316A	3–90%	0	0
Quinquenel et al. (11)	30	15/30 mutation TP534/30 mutated IGHV	2 (NA-NA)	57% (17/30)	C481S/Y/R/G	0.2–73%	R665W L845G C849R D993H	1–11%
Gángó et al. (21)#	20****	7/20 del(17p) 10/20 del(13q) 6/20 trisomy 12 3/20 del(11q)	3 (1–5)	40% (8/20)	R28S G164D R490H C481S/Y Q516K	2.7–27.3%	F82S R694H D993H S1192G	2.6–4.9%

NA, not available; CK, complex karyotype; VAF, variant allele frequency.

^*Mutation status of a patient with Richter transformation was described; resistance-associated mutation was found in peripheral blood, not in lymph nodes (19).

^**Patient characteristics for a complete set of 308 patients (13).

^***6/9 patients with Richter transformation were included (14).

^****3/20 patients with Richter transformation were included (21).