Table 2 Response to second-generation TKIs in 3L (or later) treatment of CP-CMLa,b.

From: Expert opinion—management of chronic myeloid leukemia after resistance to second-generation tyrosine kinase inhibitors

Study

TKI

Cumulative CCyR rate, %

Cumulative MMR rate, %

Median follow-up, months (range)

EFS/PFS/TTF

OS

Prior treatment failure information, n/N

Mutations in pts tested prior to 3L therapy, n/N

Garg 2009 [23] (N = 48 total group) (n = 25 CP; n = 10 AP; n = 13 BC)

Dasatinib 3L in CP-CML (n = 16)

31

13

13 (0.5–41) (all pts)

Median FFS: 20 months

Median OS: 20 months (all pts)

30/34 (all pts) failed prior 2L TKI due to resistance

11/16

Nilotinib 3L in CP-CML (n = 9)

11

33

9/14 (all pts) failed prior 2L TKI due to resistance

7/9

Ribeiro 2015 [24] (n = 18)

Dasatinib 3L (n = 5) or nilotinib 3L (n = 13)

13c

24c

52 (7–75)

5-year EFS: 22%

5-year OS: 86%

16/18 failed prior 2L TKI due to resistance and 2/18 due to intolerance

6/14

5-year PFS: 54%

Lomaia 2015 [25] (n = 53)

Dasatinib (n = 30), nilotinib (n = 18), or bosutinib (n = 5) 3L

21

NA

21 (1–67)

NA

2-year OS: 67%

48/53 pts failed one TKI 42/53 pts failed both prior TKIs

16/35 (T315I in 3 pts)

Giles 2010 [26] (n = 60 total group) (n = 39 CP; n = 21 AP)

Nilotinib 3L in CP-CML (n = 39)

24d

NA

12 (NA) (all pts)

Median TTF: 19.5 months

18-month estimated OS: 86%

12/39 failed prior 2L TKI (dasatinib) due to resistance, 26/39 due to intolerance, and 1/39 due to an undefined reason

12/25 Most common: F317L (n = 6); T315I (n = 2)

18-month estimated PFS: 59%

Cortes 2011 [27] (n = 29)e

Any TKI 3L or latere

24e

NA

NA for 3L and beyond cohort

NA

NA

NA

NA

Ibrahim 2010 [28] (n = 26)

Dasatinib or nilotinib 3Lf

35

19

21.5 (6–46.5)

30-month EFS: 46%

30-month OS: 47%

7/26 pts had prior hematologic resistance to TKI

NA

Hochhaus 2019 [29] (n = 61)

Bosutinib 3L

84 (resistant or intolerant; n = 56)g

64 (resistant or intolerant; n = 28)h

NA for 3L cohort

NA for 3L cohort

NA for 3L cohort

35/61 resistant to any prior TKI

NA

26/61 intolerant to prior TKIs

  1. 2L second-line, 3L third-line, 4L fourth-line, AP advanced phase, BC blast crisis, CML chronic myeloid leukemia, CP chronic phase, CCyR complete cytogenetic response, EFS event-free survival, FFS failure-free survival, MMR major molecular response, NA not available, OS overall survival, PFS progression-free survival, pts patients, TKI tyrosine kinase inhibitor, TTF time to treatment failure.
  2. aThe heterogeneity of the studies should be noted with some being small non-controlled studies and some being larger registrational trials.
  3. bResistant/intolerant CP-CML patients receiving ≥3L TKI are counted (unless specified as ‘all pts’).
  4. cCCyR data are based on 15 patients and MMR data are based on 17 patients.
  5. dIn Giles 2010 study, 39 patients were enrolled and 37 evaluable for response. Response data are based on 37 patients; however, resistance to 2L TKI data are based on the 39 patients enrolled.
  6. eIn Cortes 2011 study, 26 patients were treated in 3L and a further 4 in 4L (of whom 3 were evaluable). Response data are reported for all 29 evaluable patients in 3L and 4L. Of the 26 3L patients: 15 (58%) had received prior dasatinib; 7 (27%) prior nilotinib; 2 (8%) prior bosutinib; and 2 (8%) prior bafetinib.
  7. fIn Ibrahim 2010 study, data are reported together for dasatinib-treated or nilotinib-treated patients.
  8. gCumulative rates in patients evaluable for response; CCyR rate was 77% in resistant patients treated in 2/3/4L (n = 77).
  9. hCumulative rates in patients evaluable for response, excluding patients with baseline MMR; MMR rate was 46% in resistant patients treated in 2/3/4L (n = 48).
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