Table 1.

Clinical trials of TKI therapy reporting deep molecular responses (MR4 or deeper) occurring in patients with newly diagnosed CML-CP

TrialSamples, naAssay sensitivity (IS standardized?)Median f/u, moTreatment→MR endpoints assessed
IRIS (15, 24)1≥4.5 logs (established the IS)25IM 400 mg qd (n = 333) → CMR at 12 mo = 4%b
81IM 400 mg qd (n = 29c) → MR4/MR4.5 by 81 mo = 70%/52%. MR4.5 at 81 mo = 45%
ID-01_151 (66)1≥5 logs (No)15IM 400 mg b.i.d. (n = 112) → CMR = 28%
de Lavallade et al. (67)≥2 consecutiveNR (Yes)38IM 400 mg qd (n = 204d) → CMR = 5%
RIGHT (68)1≥4.5 logs (Noe)17fIM 400 mg b.i.d. (n = 115) → CMR by 6, 12, 18 mo = 39%, 44%, 55%
Verma et al. (29)1≥4.5 logs (NR)65IM 400 mg qd (n = 73) or 800 mg qd (n = 208) → CMR = 44%
SPIRIT (26)1g(Yes)47hIM 400 mg qd (n = 159) → MR4 at 12, 24 mo = 14%, 21%. CMR at 24 mo = 9%
IM 400 mg qd + AraC (n = 158) → MR4 at 12, 24 mo = 15%, 26%. CMR at 24 mo = 8%
IM 400 mg qd + PEG-IFN (n = 159) → MR4 at 12, 24 mo = 30%, 38%. CMR at 24 mo = 16%
IM 600 mg qd (n = 160) → MR4 at 12, 24 mo = 17%, 26%. CMR at 24 mo = 8%
CML Study IV (27)1NR (Yes)43IM 400 mg qd (n = 324) → MR4 by 12, 24, 36 mo = 8%, 31%, 46%
48IM 400 mg qd + IFN-α (n = 350) → MR4 by 12, 24, 36 mo = 12%, 30%, 41%
28IM 800 mg qd (n = 338) → MR4 by 12, 24, 36 mo = 20%, 43%, 57%
ENESTnd (10)1i(Yes)Min 36NIL 300 mg b.i.d. (n = 282) → MR4 by 1, 3 y = 20%, 50%. MR4.5 by 1, 3 y = 11%, 32%
NIL 400 mg b.i.d. (n = 281) → MR4 by 1, 3 y = 15%, 44%. MR4.5 by 1, 3 y = 7%, 28%
IM 400 mg qd (n = 283) → MR4 by 1, 3 y = 6%, 26%. MR4.5 by 1, 3 y = 1%, 15%
ENEST1st (69)1NR (Yes)6.5fNIL 300 mg b.i.d. (n = 205) → MR4 by 3, 6 mo = 5%, 20%
GIMEMA (70, 71)1; stable, 3 × 4 mo apart≥4 logs (Yes)48NIL 400 mg b.i.d. (n = 73) → MR4 at 12, 24, 36 mo = 12%, 27%, 25%
51NIL 400 mg b.i.d. (n = 73) → Stable MR4 = 25%
MDACC NIL phase II (72)1≥5 logs (Yes)17.3NIL 400 mg b.i.d. (n = 51) → CMR by 6, 12, 30 mo = 4%, 11%, 15%
Nicolini et al. (73)1NR (Yes)13.6NIL 300 mg b.i.d. + PEG-IFN (n = 40) → MR4 at 6, 12, 15 mo = 23%, 57%, 80%. MR4.5 at 6, 12, 15 mo = 10%, 21%, 50%. MR5 at 6, 12, 15 mo = 10%, 15%, 40%
DASISION (9)1NR (Yes)Min 24DAS 100 mg qd (n = 259) → MR4.5 by 2 y = 17%
IM 400 mg qd (n = 260) → MR4.5 by 2 y = 8%
S0325 (74)1NR (j)36DAS 100 mg qd (n = 99) → MR4/MR4.5 at 1 y = 27%/21%
IM 400 mg qd (n = 91) → MR4/MR4.5 at 1 y = 21%/15%
MDACC DAS phase II (75)1≥5 logs (Yes)24DAS 100 mg qd or 50 mg b.i.d. (n = 50) → CMR at 6, 12, 30 mo = 0%, 7%, 0%
BELA (76)1≥4 logs (Yes)13.8fBOS 500 mg qd (n = 250) → MR4 at 12 mo = 12%
IM 400 mg qd (n = 252) → MR4 at 12 mo = 3%

Abbreviations: AraC, cytarabine; BELA, Bosutinib Efficacy and Safety in Chronic Myeloid Leukemia; b.i.d., twice daily; BOS, bosutinib; DAS, dasatinib; DASISION, Dasatinib Versus Imatinib Study in Treatment-Naive CML patients; ENEST1st, Evaluating Nilotinib Efficacy and Safety in Clinical Trials as First-Line Treatment; ENESTnd, Evaluating Nilotinib Efficacy and Safety in Clinical Trials–Newly Diagnosed Patients; f/u, follow-up; GIMEMA, Gruppo Italiano Malattie Ematologiche dell'Adulto; IM, imatinib; IRIS, International Randomized Interferon Versus STI571; IS, International Scale; MDACC, MD Anderson Cancer Center; min, minimum; MR, molecular response; NIL, nilotinib; NR, not reported; qd, daily; PEG-IFN, pegylated interferon α-2a; qd, once daily; RIGHT, Rationale and Insight for Gleevec High-Dose Therapy; SPIRIT, STI571 Prospective Randomized Trial; SWOG, Southwest Oncology Group.

  • aNumber of samples required to meet criteria for response.

  • bPatients with CCyR only.

  • cSubgroup analysis of patients enrolled in the IRIS study in Australia and New Zealand from June 2000 to February 2007.

  • dNote: 17 of these patients were also in the IRIS study.

  • eBaseline BCR–ABL1/ABL1 ratio based on prestudy samples from participating laboratory.

  • fMedian exposure.

  • g≥25,000 copies of ABL were required for a sample to be considered adequate.

  • hFor all patients; 48 mo for patients alive as of data cutoff.

  • i≥3,000 copies of ABL were required for a sample to be considered adequate.

  • jStandardized to SWOG-specific BCR–ABL1 baseline level.