medwireNews: A review of tyrosine kinase inhibitor (TKI) therapy in Japanese patients with chronic myeloid leukaemia (CML) demonstrates high rates of treatment response and good outcomes but highlights the various issues associated with treatment discontinuation.
The study included information for 51 patients who received front-line treatment with a first-generation TKI (86.3%) or a second-generation TKI (13.7%) between 2002 and 2014 at the Miyazaki Prefectural Miyazaki Hospital.
Thirteen patients switched from a first- to a second-generation TKI, report Noriaki Kawano, from the same institution, and colleagues.
The majority (n=48) of patients had chronic phase disease, two had accelerated phase and one patients was in blast crisis.
Overall, a complete cytogenetic response (CCyR) was achieved in 90.2% of patients, while 78.4% achieved a major molecular response (MMR).
The researchers compared these rates at 3, 6, 12 and 18 months of treatment for patients given first-generation, second-generation and second-line TKI therapy, finding that the effectiveness of second-line second-generation therapy was “almost equivalent” to front-line first-generation TKI therapy, despite including patients who had developed resistance.
Indeed, the researchers say the patients given second-generation TKI as a front-line therapy may have “tended to achieve an earlier response” than those given a first-generation TKI. A “good response” was reported for CCyR rates at 3 and 6 months, MMR at 6 and 12 months and MR4 rates at 6, 12 and 18 months in these individuals.
“In our study, we had excellent efficacy demonstrated by excellent response and good survival rates that were consistent with previous reports”, the team writes.
After 5 years, 93.7% of patients were alive. Four patients died, including one patient in accelerated phase and another in chronic phase. Two patients with CCyR status using a first-generation TKI went into sudden blast crisis. Although both patients attained complete remission with further TKI therapy and haematopoietic stem cell transplantation, both later died from opportunistic infection.
The majority of patients experienced adverse events from TKI therapy, with grade 1–3 events reported by 64.7%. Grade 3 events occurred in 11.8%, including skin rash, glucose intolerance and pleural effusion.
Low-dose therapy was given to four CML patients with grade 3 side effects and after dose-escalation a full dose was achieved. Two elderly patients with cardiovascular complications were also given long-term low-dose TKI therapy.
“Dose reduction, replacement with another TKI, or low dose TKI treatment may be useful methods to control side effects”, the authors summarise in the Journal of Clinical and Experimental Hematopathology.
TKI therapy was also discontinued in three patients because of economic difficulties and a fourth patient who was pregnant. Although these patients had all achieved CCyR, their BCR–ABL transcript levels progressed after discontinuation.
“These findings suggest that management of the latter clinical and social challenges may be essential to achieve optimal treatment response and outcomes for CML patients in clinical practice”, the authors conclude.
Indeed, further research is “essential” to clarify the potential side effects of TKI in pregnant mothers and infants, they add.
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