Background: With BCR::ABL1 tyrosine kinase inhibitor (TKI) therapy, most patients with chronic-phase chronic myeloid leukemia (CML-CP) can achieve complete cytogenetic response (CCyR) within 6 months of therapy. However, no studies have investigated patients who do not achieve CCyR yet maintains stable disease on long-term TKI treatment. Here we investigated 30 CML-CP patients who did not achieve CCyR but remained free of blastic progression for at least 10-year while on TKI therapy.

Methods: Patients diagnosed with CML-CP or accelerated phase who received at least 10 years of TKI treatment, did not achieve CCyR, yet remained free of blastic progression for a minimum of 10 consecutive years during treatment, were included.

Results: At TKI initiation, the median blast count in the bone marrow was 2%. During TKI therapy, 16 patients had additional chromosomal abnormalities (ACAs). The most common ACAs were +Ph (n = 9) and +8 (n = 8), mostly transient, while high-risk ACAs were less common (n = 3). BCR::ABL1 kinase domain mutations were detected in 20 patients, 12 patients having a single mutation, mostly transient, and 8 having multiple mutations, which were mostly persistent cross TKI therapies. After a median of 4 TKI lines, the best responses included complete hematologic response (CHR) (n = 15), minor cytogenetic response (n = 2), partial cytogenetic response (n = 10), and major molecular response beyond the 10-year period without CCyR (n = 3). Among 15 patients who achieved a response better than CHR, 14 eventually lost their response. After a median follow-up of 245 months from TKI initiation, 6 patients progressed to blast phase after a median of 165 months.

Conclusions: Despite not achieving CCyR, most patients in this cohort maintained long-term stable disease. With careful monitoring and individualized TKI treatment, long-term survival may still be achievable in some non-CCyR responders who do not opt for allogenic stem cell transplantation.