Program: Oral and Poster Abstracts
Session: 632. Chronic Myeloid Leukemia: Therapy: Poster I
Methods: Among adult CML patients in the chronic phase diagnosed at Hiroshima Red Cross Hospital & Atomic-bomb Survivors Hospital from May 1995 to September 2010, we analyzed patients who achieved and maintained CMR for >1 year on TKIs, and then stopped TKIs. We started TKI treatment with IMA in all patients and changed to NIL or DAS after March 2009, when second-generation TKIs became available in Japan. We continued each TKI for ³6 months, and for >12 months in most cases. Molecular monitoring was performed with BCR-ABL1 real-time quantitative PCR (RQ-PCR) using bone marrow or peripheral blood samples. Sensitivity of this RQ-PCR was 0.004%, corresponding to MR4.4. Relapse was defined as a loss of CMR. We provided TKI therapy for relapsed patients. RQ-PCR was performed every three months after relapse.
Results: Stopping TKI was possible in 51 patients (32 males, 19 females). Observations were continued until June 2015, and the median duration of observation was 147 months (range, 59-257 months). Interferon (IFN)-α was administered to 18 patients. Median age at diagnosis was 44 years (range, 22-83 years). Two deaths were observed, with neither due to CML. Median duration of TKI treatment was 91 months (range, 29-160 months). Median interval from starting TKIs until achieving CMR was 41 months (range, 6-144 months), and that from achieving CMR to stopping TKIs was 20 months (range, 10-91 months). Median duration of observation from stopping TKIs was 42 months (range, 4-135 months). TKI treatment comprised IMA alone in 10 patients, IMA → NIL in 8, and IMA →NIL → DAS in 33. Relapse after stopping TKIs was observed in 14 cases. The period from stopping TKIs to relapse was 3 months in 12 patients, and 6 months and 18 months in 1 patient each. We treated all relapse patients with TKIs as patients chose, and all achieved 2nd CMR. Median period from relapse to 2nd CMR was 20.5 months (range, 6-40 months). In univariate analysis by Fisher’s exact test, no correlation was seen between relapse rate and sex (male, n=32 vs. female, n=19; p=0.106), history of IFN-α therapy (yes, n=18 vs. no, n=33; p=0.525), duration from achieving CMR to stopping TKI (³24 months, n=34 vs, <24 months, n=17; p=0.183), and use of second-generation TKI (yes, n=34 vs. no, n=10; p=0.25). However, relapse rate was significantly lower in patients who received second-generation TKIs for ³24 months (n=23 vs. <24 months, n=10; p=0.0425).
Conclusions: In our cohort, the rate of relapse after stopping TKIs was lower among patients who received second-generation TKIs for a longer period. This suggests that achieving deeper molecular response may be more important than maintaining CMR for a long time when trying to stop TKIs. The fact that most relapses after stopping TKIs occurred 3 months after stopping TKIs implies a need for careful molecular monitoring, particularly just after stopping TKIs.
Disclosures: No relevant conflicts of interest to declare.
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