PB1948 LONG‐TERM CLINICAL OUTCOMES OF CHRONIC‐PHASE CHRONIC MYELOID LEUKEMIA PATIENTS TREATED WITH IMATINIB AS INITIAL THERAPY
Authors: Shiseki M. , Yoshinaga K. , Ishiyama M. , Mori N. , Tanaka J. 
Published: June 2019

Background:

Clinical outcomes of chronic‐phase chronic myeloid leukemia (CP‐CML) patients markedly improved by introduction of tyrosine kinase inhibitors (TKIs). Particularly, second generation TKIs are more potent, and induce faster and deeper response in CP‐CML patients compared to first generation TKI, imatinib. However, cardiovascular toxicities due to long‐term treatment by second generation TKIs are current major concern. Imatinib showed relatively less cardiovascular toxicity and may be safer in long‐term treatment than second generation TKIs.

Aims:

The aim of this study was to elucidate long‐term clinical outcomes of the CP‐CML patients treated with imatinib as initial therapy.

Methods:

In the present study, we retrospectively analyzed CP‐CML patients who received imatinib as a first line TKI therapy in Tokyo Women's Medical University hospital. This study was was conducted in accordance with the Declaration of Helsinki and reviewed by an institutional ethics committee.

Results:

A total of 56 patients (39 males) with median age of 56.5 years (range, 20‐83 years) at diagnosis were analyzed in the study. Seventeen patients received interferon‐alfa treatment prior to imatinib. Median follow‐up period from diagnosis was 13.2 years (range,0.7‐24.9 years). Median duration of imatinib therapy was 9.6 years (range, 0.3‐16.2 years). Estimated median overall survival time was 24.2 years, and 3‐, 5‐, and 10‐year overall survival rates were 96.4%, 92.7%, and 88.6%, respectively. Second primary neoplasms were developed in 11 of 56 (19.6%) patients during follow‐up period. Among these 11 patients, one patient developed malignant lymphoma, remaining 10 patients developed solid tumors: colorectal cancer (n = 4), gastric cancer (n = 1), pancreatic cancer (n = 1), lung cancer (n = 1), bladder cancer (n = 1), prostate cancer (n = 1), and head and neck cancer (n = 1). Surgical resection was undergone in five patients, and seven patients received chemotherapy. A total of 11 patients died during follow‐up period. Most common cause of death was second primary neoplasm (n = 5), followed by cardiovascular event (n = 4). No leukemia‐related deaths were recorded.

In 17 patients, imatinib was switched to second generation TKIs, dasatinib (n = 10) or nilotinib (n = 7), because of intolerance (n = 7), treatment failure (n = 4), and other reasons (n = 6), including clinical trials, and patient's request. Among remaining 39 patients who were continuously treated with imatinib with median treatment duration of 11.2 years (range, 0.7‐16.2 years), 35 patients achieved major molecular response (MR3.0) at last follow up. Among these 35 patients, 23 patients achieved deep molecular response (MR4.0). Therefore, 59% (23/39) of patients treated with imatinib subsequently achieved MR4.0. Nine patients, who maintained deep molecular response (MR4.0) with imatinib treatment for at least two years, discontinued imatinib. Median duration of imatinib treatment in these nine patients was 10.5 years (range, 5.7‐13.8 years). Eight of nine patients are maintaining treatment‐free remission with median observation period of 34 months (range, 20‐42 months) at last follow up.

Summary/Conclusion:

By long‐term imatinib treatment, substantial number of patients achieved deep molecular response, and significant number of patients may have possibility of treatment‐free remission. No leukemia‐related deaths were recorded in cohort of the present study. However, careful management of co‐morbidity and regular screening for second primary neoplasms should be required.