Rates of deep molecular response by digital and conventional PCR with frontline nilotinib in newly diagnosed chronic myeloid leukemia: a landmark analysis

Figures & data

Table 1. Baseline characteristics.

	Nilotinib 300 mg twice daily N = 128
Median age (range), years	56.5 (21–89)
Male, n (%)	64 (50.0)
Race, n (%)
White	103 (80.5)
Black	16 (12.5)
Asian	5 (3.9)
Other	4 (3.1)
Prior antineoplastic medication, n (%)^a	52 (40.6)
Hydroxyurea	40 (31.3)
Nilotinib	10 (7.8)
Imatinib	4 (3.1)
Dasatinib	2 (1.6)
Sokal risk score, n (%)
Low	58 (45.3)
Intermediate	43 (33.6)
High	24 (18.8)
Unknown	3 (2.3)
BCR-ABL1^IS level at screening, n (%)
>10%	118 (92.2)
>1% to ≤10%	1 (0.8)
>0.1% to ≤1%	0
>0.01% to ≤0.1%	1 (0.8)
>0.0032% to ≤0.01%	0
≤0.0032%	3 (2.3)
Missing	5 (3.9)

IS: International Scale.

a No patients received prior treatment with interferon (with or without cytarabine) or anagrelide.

Table 2. Molecular responses with up to 24 months of on-study treatment.

	Nilotinib 300 mg twice daily N = 128
	All patients	Patients who achieved and lost response	Patients who achieved and did not lose response
Cumulative rate of MMR by 24 months, n (%)	94 (73.4)	NA	NA
Loss of MMR, n/N (%)	13/94 (13.8)	NA	NA
Median (range) time to MMR, months^a	5.6 (0.9–18.1)	8.4 (0.9–18.1)	5.6 (0.9–16.8)
Median (range) duration of MMR, months^a^,^b	16.5 (0–21.1)	3.15 (0.5–19.4)	16.6 (0–21.1)
Cumulative rate of confirmed MR^4.5 by 24 months, n (%)	34 (26.6)	NA	NA
Loss of confirmed MR^4.5, n/N (%)	6/34 (17.6)	NA	NA
Median (range) time to confirmed MR^4.5, months^c	8.3 (1.9–17.5)	11.3 (3.2–16.6)	8.0 (1.9–17.5)
Median (range) duration of confirmed MR^4.5, months^b^,^c	13.9 (4.6–20.3)	5.8 (5.3–13.6)	14.0 (4.6–20.3)

IS: International Scale; MMR: major molecular response (BCR-ABL1^IS ≤0.1%); MR^4.5: BCR-ABL1^IS ≤0.0032%; NA: not applicable.

a Data are reported for all patients who achieved MMR (n = 94), patients who achieved and lost MMR (n = 13), and patients who achieved and did not lose MMR (n = 81).

b For patients who did not lose response, the date of the last dose of study drug was used as the end date for the analysis of duration of response.

c Data are reported for all patients who achieved confirmed MR^4.5 (n = 34), patients who achieved and lost confirmed MR^4.5 (n = 6), and patients who achieved and did not lose confirmed MR^4.5 (n = 28).

Figure 1. Change in BCR-ABL1^IS over time based on achievement of BCR-ABL1^IS ≤10% at 3 months (patients who had MMR or MR^4.5 at baseline were excluded from this analysis. The number of evaluable patients at each time point is indicated). IS: International Scale; MMR: major molecular response (BCR-ABL1^IS ≤0.1%); MR^4.5: BCR-ABL1^IS ≤0.0032%; SD: standard deviation.

Table 3. Landmark analysis of molecular response according to BCR-ABL1^IS at 3 months on study.

	Patients with BCR-ABL1^IS ≤10% at 3 months	Patients without BCR-ABL1^IS ≤10% at 3 months
Analysis of MMR, n^a	87	10
Achieved MMR on study, n (%)	75 (86.2)	2 (20.0)
Time to MMR, n (%)
<3 months	13 (14.9)	0
3 to <6 months	37 (42.5)	0
6 to <12 months	18 (20.7)	1 (10.0)
12 to <18 months	6 (6.9)	1 (10.0)
18 to <24 months	1 (1.1)	0
≥24 months	0	0
Analysis of confirmed MR^4.5, n^b	87	10
Achieved confirmed MR^4.5 on study, n (%)	28 (32.2)	0
Time to confirmed MR^4.5, n (%)
<3 months	0	0
3 to <6 months	12 (13.8)	0
6 to <12 months	9 (10.3)	0
12 to <18 months	7 (8.0)	0
18 to <24 months	0	0
≥24 months	0	0

IS: International Scale; MMR: major molecular response (BCR-ABL1^IS ≤0.1%); MR^4.5: BCR-ABL1^IS ≤0.0032%; TKI: tyrosine kinase inhibitor.

a Patients with MMR at baseline and patients with prior TKI treatment were excluded from landmark analyses of MMR.

b Patients with MR^4.5 at baseline and patients with prior TKI treatment were excluded from landmark analyses of MR^4.5.

Figure 2. Change in detectable BCR-ABL1 transcript levels over time by Fluidigm digital PCR after achievement of confirmed MR^4.5. Data are shown with linear regression and cubic spline fits as raw copy numbers (panel A) and after log transformation (panel B). The reproducibility of the estimated BCR-ABL1 level of 3 panels per sample (see Methods) was good (standard deviation, mean, 30.5 copies; median, 0 copies). MR^4.5: BCR-ABL1 ≤0.0032% on the International Scale; PCR: polymerase chain reaction; RCSpline: restricted cubic spline.