Seven-Year Follow-up of Patients Receiving Imatinib for the Treatment of Chronic Myelogenous Leukemia by the TARGET System
Authors: Tauchi Tetsuzo , Kizaki Masahiro , Okamoto Shinichiro , Tanaka Hideo , Tanimoto Mitsune , Inokuchi Koiti , Murayama Tohru , Saburi Yoshio , Hino Masayuki , Tsudo Mitsuru , Shimomura Taizo , Isobe Yasushi , Oshimi Kazuo , Dan Kazuo , Ohyashiki Kazuma , Ikeda Yasuo 
Published: October 2019

Abstract
Abstract 2287
The TARGET system is an online database that can be easily accessed by physicians. The TARGET system is operated by the Japanese Society of Hematology. The registration of one's own chronic myeloid leukemia (CML) patients in the TARGET system makes it possible to share experiences among physicians, and, thus, may facilitate appropriate treatment for patients. Patients participating in clinical trials are usually selected according to strict eligibility criteria. Previous publications have questioned the use of other overly restrictive exclusion criteria in clinical oncology trials. In practical situations, however, the clinical features of patients are much more heterogeneous than those defined by the selection criteria in clinical trials. From this point of view, the TARGET system might provide more practical and general features compared with the IRIS study. Patients were registered in the TARGET system from October 2003 to March 2010 in Japan. A total of 1,236 patients from 176 hospitals were registered in Japan. We analyzed data from 639 CML chronic phase patients not receiving prior therapy registered in this system. After 90 months follow-up, high survival rates were demonstrated for imatinib-treated newly diagnosed CML patients, with event-free survival (EFS), progression-free survival (PFS), and overall survival (OS) rates of 79.1, 94.8, and 95.1%, respectively. A landmark analysis of 296 patients who showed a complete cytogenetic response (CCyR) at 12 months after the initiation of imatinib treatment revealed that, at 90 months, 99% of patients (95% CI, 98 to 100) had not progressed to accelerated phase (AP) or blastic crisis (BC). The patients showing a CCyR and a reduction of at least 3 log levels of BCR-ABL transcripts after 18 months of treatment had an estimated survival rate without CML progression of 100% at 84 months.By 84 months, 315 patients had achieved an MMR. A total of 226 of 315 patients (71.7%) achieved undetectable BCR-ABL by 84 months. We therefore analyzed the probability of achieving undetectable BCR-ABL based on the molecular response at 12 and 18 months. The probability of achieving undetectable BCR-ABL by 72 months in patients with an MMR at 12 months was 86.5%, compared with 64.7% for those without an MMR (P<0.0001). Also, the probability of achieving undetectable BCR-ABL based on the molecular response for patients with an MMR at 18 months was 91.9%, compared with 65.3% for those without an MMR (P<0.0001). Therefore, having an MMR at 12 or 18 months of imatinib therapy is highly predictive of subsequent undetectable BCR-ABL. However, the TARGET data indicate a marked increase in the number of patients with undetectable BCR-ABL without an MMR at 12 months compared with IRIS sub-meta-analysis (64.7 vs. 5%, respectively). There were no new safety issues. In summary, based on this 7-year TARGET analysis, imatinib showed a continual clinical benefit as first-line therapy for newly diagnosed CML. The data from TARGET shows that Japanese patients contain a large number of late responders to imatinib therapy. The TARGET system may represent a more practical and general feature compared with the IRIS study.

Disclosures:
Tauchi: Novartis Pharma KK: Research Funding.