Dasatinib discontinuation in patients with chronic-phase chronic myeloid leukemia and stable deep molecular response: the DASFREE study

Figures & data

Table 1. Baseline patient characteristics.

	All enrolled patients (N = 84)
Age, median (range), years	52 (24–80)
Male, n (%)	47 (56)
ECOG PS, n (%)
0	68 (81)
1	11 (13)
Not reported	5 (6)
Line of therapy, n (%)
First	37 (44)
Subsequent	47 (56)
Resistant	25 (53)
Intolerant	18 (38)
Other	4 (9)
Prior treatment, n (%)
Imatinib	44 (52)
Ponatinib	1 (1)
Imatinib + nilotinib	2 (2)
Interferon	0
Sokal score, n (%)^a
Low	54 (64)
Intermediate	24 (29)
High	5 (6)
Unknown	1 (1)
Median time in prior MR^4.5, months (range)
Any line of therapy	28 (13–116)
First line	27 (13–68)
Subsequent lines	35 (14–116)
Median time from diagnosis to discontinuation, months (range)	69 (29–244)
Median dose at discontinuation, mg (range)	100 (20–150)

^aThe initial study protocol excluded patients with high Sokal risk scores; the study protocol was later amended after 35 patients had already enrolled. ECOG PS: Eastern Cooperative Oncology Group performance status; MR^4.5: sustained deep molecular response (BCR-ABL1 ≤ 0.0032% on the International Scale).

Figure 1. TFR in all enrolled patients at 2 years (N = 84). CI: confidence interval; NE: not estimable; TFR: treatment-free remission.

Figure 2. Loss and recovery of MMR and MR^4.5 at 2 years. ^aA 52-year-old male with low-risk CML treated with first-line dasatinib 100 mg once daily for 40 months discontinued the study after 33 months in MR^4.5. This patient maintained BCR-ABL1 transcript levels between 0.0017 and 0.01 for 3 years and had an increase to 0.1% in month 39, which was confirmed on a second occasion in month 42 (0.11%). ^bOne patient lost MMR and restarted treatment. This patient discontinued the study after only one follow-up molecular assessment and therefore was not considered evaluable for molecular response. CML: chronic myeloid leukemia; MMR: major molecular response; MR^4.5: BCR-ABL1 ≤ 0.0032% on the International Scale.

Figure 3. Multivariate analysis of TFR and covariates at 2 years. CI: confidence interval; MR^4.5: BCR-ABL1 ≤ 0.0032% on the International Scale; TFR: treatment-free remission; TKI: tyrosine kinase inhibitor.

Table 2. All causality adverse events in ≥4% of enrolled patients and withdrawal events in all enrolled patients.

Patients with AEs, n (%)	Patients off treatment after discontinuing dasatinib (n = 84)		Patients on treatment after restarting dasatinib (n = 45)
	Any grade	Grade 3–4	Any grade	Grade 3–4
Blood and lymphatic disorders	3 (4)	0	7 (16)	1 (2)
Neutropenia	0	0	3 (7)	1 (2)
Gastrointestinal disorders	12 (14)	0	13 (29)	0
Upper abdominal pain	1 (1)	0	2 (4)	0
Constipation	1 (1)	0	3 (7)	0
Diarrhea	1 (1)	0	4 (9)	0
Dyspepsia	1 (1)	0	2 (4)	0
Abdominal pain	0	0	2 (4)	0
Dry mouth	0	0	3 (7)	0
General disorders	11 (13)	0	15 (33)	0
Peripheral edema	3 (4)	0	2 (4)	0
Asthenia	2 (2)	0	5 (11)	0
Fatigue	2 (2)	0	8 (18)	0
Pyrexia	2 (2)	0	2 (4)	0
Pain	0	0	2 (4)	0
Investigations	8 (18)	3 (7)	12 (14)	2 (2)
Increased blood creatinine	0	0	2 (4)	0
Metabolic disorders	6 (7)	0	9 (20)	0
Hypercholesterolemia	0	0	3 (7)	0
Hypokalemia	0	0	2 (4)	0
Hypophosphatemia	0	0	2 (4)	0
Infections and infestations	18 (21)	2 (2)	15 (33)	2 (4)
Nasopharyngitis	7 (8)	0	5 (11)	0
Sinusitis	4 (5)	0	2 (4)	0
Urinary tract infection	2 (2)	0	2 (4)	0
Cellulitis	0	0	2 (4)	0
Pharyngitis	0	0	2 (4)	0
Pneumonia	0	0	2 (4)	0
Musculoskeletal and connective tissue disorders	30 (36)	2 (2)	11 (24)	0
Arthralgia	11 (13)	0	4 (9)	0
Back pain	6 (7)	0	2 (4)	0
Myalgia	6 (7)	0	4 (9)	0
Arthritis	4 (5)	0	0	0
Pain in extremity	4 (5)	0	2 (4)	0
Musculoskeletal pain	3 (6)	0	2 (4)	0
Nervous system disorders	12 (14)	0	13 (29)	3 (7)
Headache	8 (10)	0	6 (13)	0
Dizziness	1 (1)	0	3 (7)	0
Memory impairment	0	0	2 (4)	0
Syncope	0	0	2 (4)	2 (4)
Psychiatric disorders	6 (7)	0	11 (24)	0
Depression	1 (1)	0	3 (7)	0
Insomnia	0	0	2 (4)	0
Anxiety	2 (2)	0	2 (4)	0
Respiratory disorders	5 (6)	0	9 (20)	1 (2)
Dyspnea	1 (1)	0	2 (4)	0
Dyspnea exertional	1 (1)	0	2 (4)	0
Pleural effusion	1 (1)	0	3 (7)	1 (2)
Cough	0	0	2 (4)	0
Skin and subcutaneous tissue disorders	15 (18)	0	6 (13)	0
Rash	4 (5)	0	2 (4)	0
Vascular disorders	9 (11)	2 (2)	2 (4)	0
Hypertension	9 (11)	2 (2)	1 (2)	0
	Patients with withdrawal events (n = 9)
Withdrawal events^a, n	15
Time from discontinuation to withdrawal event onset/worsening, median (range), months	4 (<1–18)
Withdrawal events resolved, n	9
Spontaneous resolution without medication (other than a TKI)	7
Resolution after non- TKI/nonanalgesic medication	2
Time from withdrawal event onset to resolution, median (range), months	5 (1–12)

AE: adverse event; TKI: tyrosine kinase inhibitor.

a Withdrawal events were defined as any adverse event occurring and/or worsening due to treatment cessation, as determined by the investigator.

Data availability statement

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