Table 3 Efficacy and safety results from prospective clinical trials of TKIs in the 3L
From: Third-line therapy for chronic myeloid leukemia: current status and future directions
Trial | Efficacy | Safety |
|---|---|---|
A phase I/II trial of 3L + bosutinib in patients with CML-CP resistant/intolerant to imatinib + dasatinib and/or nilotinib   (Study 200) [18] | At 4 years:  74% cumulative cCHR   63% probability of maintaining cCHR  40% cumulative MCyR   69% probability of maintaining MCyR  24% cumulative incidence of on-treatment CML-AP/BC or death and 22% on-study deaths  78% KM-estimated OS | TEAEs reported in 100% of patients and grade 3/4 TEAEs reported in 68.1% of patients Most common TEAEs were diarrhea (83%), nausea (48%), vomiting (38%), and thrombocytopenia (39%) |
Overall, in patients with CML-CP [19]:  60% achieved MCyR at any time, of whom 54% achieved CCyR  40% achieved MMR  24% achieved MR4.5  3% of patients transformed to CML-AP/BC  KM-estimated PFS and OS at 5 years was 53% and 73%, respectively In a study of patients with CML-CP and resistance/intolerance to nilotinib or dasatinib or who had a T315I mutation [46]:  51% of patients with intolerance/resistance and 70% with T315I mutation achieved MCyR, with 40% and 66% achieving CCyR, respectively  MMR was achieved in 27% of patients with resistance/intolerance to nilotinib or dasatinib and 56% of patients with a T315I mutation  12% of patients discontinue use due to AEs | In patients with CML-CP [19]:  Most common TEAEs  (≥ 40%) were rash (47%), abdominal pain (46%), thrombocytopenia (46%), headache (43%), dry skin (42%), and constipation (41%)  Most common grade 3/4 TEAEs (≥ 10%) were thrombocytopenia (35%), neutropenia (17%), hypertension (14%), increased lipase (13%), abdominal pain (10%), and anemia (10%)  31% of patients had AOEs In a study of patients with CML-CP and resistance/intolerance to nilotinib or dasatinib or who had a T315I mutation [46]:  Common AEs were thrombocytopenia (37%), rash (34%), dry skin (32%), and abdominal pain (22%)  Serious arterial thrombotic events occurred in 9% of patients, with 3% considered to be treatment related  12% of patients discontinued use because of AEs |