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Abstract: EP668

Type: E-Poster Presentation

Session title: Chronic myeloid leukemia - Clinical

Background
Previously reported results from JALSG CML212 (UMIN000007909), a multicenter open-labeled prospective randomized controlled phase 3 study on de novo chronic myeloid leukemia in chronic phase (CML-CP), showed that cumulative achievement rates of MR^4.5 (BCR-ABL1 ≤0.0032% on the International Scale [BCR-ABL1^IS]) by 18 months were 33.0% (75/227) (95% CI:27.0–39.6%) in the nilotinib arm and 30.8% (70/227) (95% CI: 24.9–37.3%) in the dasatinib (DAS) arm, with no significant difference.

Aims
JALSG D-STOP216 (UMIN000024985), the next planned study, will evaluate patients with sustained MR^4.5, for at least 2 years on frontline DAS for estimating the rate of treatment-free remission (TFR), which is a new treatment goal in CML-CP.

Methods
BCR-ABL-positive CML-CP patients with ≥3 years of frontline DAS and sustained MR^4.5 for more than 2 years were enrolled in this trial. Patients restarted DAS after loss of major molecular response (MMR; BCR-ABL1^IS ≤0.1%). The data cutoff was December 14, 2020, by which point all patients had completed 12 months of TFR, restarted DAS, or discontinued the study. All patients provided informed consent.

Results

A total of 56 patients were registered from 25 institutes. Forty-nine of these patients were diagnosed with FAS and PPS[A1] . Median age of the patients was 52 years (24–80 years). Sokal low-, intermediate-, and high-risk group proportions were 40.8%, 44.9%, and 14.3%, respectively. EUTOS low- and high-risk group proportions were 91.8% and 8.2%, respectively. The median duration of DAS treatment was 51 months (36–129 months), and the median duration of MR^4.5 (BCR-ABL1^IS ≤0.0032%) was 30 months (24–64 months). The median time to achieve MMR was 178 days (83–1921 days). At 12 months, 29/49 patients remained in TFR (59.2%; 95% CI: 44.2%–73.0%), and 20 patients (40.8%) lost MMR. All the 22 patients (100%) who restarted DAS, regained MMR within 6 months. At 12 months, 27/49 patients remained in MR^4.0 (BCR-ABL1^IS ≤0.01%) (55.1%; 95% CI: 40.2%–69.3%), 22 patients (44.9%) lost MR^4.0, and among 25/49 patients that remained in MR^4.5 (51.0%; 95% CI: 36.3%–65.6%), 24 patients (49.0%) lost MR^4.5. No patients experienced disease progression or death for any reason. At 24 months, the treatment-free survival (TFS) rate was 59.2% (95% CI: 44.2%–71.4%; Fig.1). TFS did not differ among Sokal risk groups (low, int, and high; p=0.6300), EUTOS risk groups (low and high; p=0.4613), duration of DAS (<4 years and > ≥ 4 years; p=0.8522), duration of MR^4.5 (<30 and ≥ 30 months; p=0.8974), or time of MMR (<178 days and ≥ 178 days; p=0.1318).

Conclusion

JALSG D-STOP216 provides prospective TFR data in Japanese patients with CML-CP who achieved sustained MR^4.5 on frontline DAS. After stopping DAS, 59.2% of patients remained in TFR 12 months later. The results suggest that a higher proportion of patients with CML-CP who achieved sustained MR^4.5 on frontline DAS will remain progression free without treatment compared with that in previous TFR trials.

Keyword(s): Chronic myeloid leukemia, Treatment-free remission, Tyrosine kinase inhibitor