Second-line tyrosine kinase treatment in patients with chronic myeloid leukemia who have failed first-line treatment

This study aimed to investigate second-line tyrosine kinase inhibitor (TKI) treatment in patients with chronic-phase chronic myeloid leukemia (CP-CML) who had failed first-line TKI treatment. 

This study concluded that these patients have good outcomes with second-line TKI treatment.  

Tyrosine kinase inhibitors (TKIs) are a type of targeted therapy used to treat chronic myeloid leukemia (CML). Imatinib (Imbruvica) is a TKI that can be used for first-line treatment of CML. First-line treatment is the standard treatment and aims to cure the cancer.  

Nilotinib (Tasigna) and dasatinib (Sprycel) are TKIs that can be used as second-line treatments for CML. Second-line treatments are those used when the first-line treatment fails due to drug resistance or intolerance.  

It was unknown if the outcomes would be favorable for CP-CML patients who received second-line TKI treatment.  

This study involved 82 patients with chronic phase CML (CP-CML) who had previously received first-line TKI treatment which failed due to resistance and/or intolerance. 93% of patients received imatinib as first-line TKI. 55% of patients involved received nilotinib as a second-line TKI. 45% of patients involved received dasatinib as a second-line TKI.  

96% of patients who received second-line TKI treatment achieved complete hematological response (CHR). CHR is when all the blood cell counts have returned to normal. 60% of patients who received second-line TKI treatment achieved a complete cytogenic response (CCyR). CCyR is when there are no Philadelphia (Ph+) chromosomes found in the blood. Ph+ chromosomes are found when cancer is present.  

The estimated 3-year progression-free survival (PFS) rate after enrollment was 98.7%. The probability of achieving CCyR was 89.3%. The probability of achieving a major molecular response (MMR) was 87.2%. MMR is when there is a low level of BCR-ABL gene (found in cancer cells). No new safety problems were reported.

This study concluded that patients with CP-CML who are resistant and/or intolerant to a 1st-line TKI can achieve an extremely good outcome with 2nd-line TKI treatment. 

This study had a limited number of participants and it was conducted in Japan. Larger studies in more diverse populations are necessary for stronger evidence. This study received funding support from Novartis Pharmaceuticals and Bristol-Myers Squibb, the manufacturers of nilotinib and dasatinib.