The discontinuation of tyrosine kinase inhibitors (TKIs) was demonstrated to be safe, and without apparent limitations on treatment-free remission (TFR) for patients with chronic myeloid leukemia (CML), in an analysis of the Life After Stopping TKIs (LAST) study, the largest study of its kind in the United States. Results of this analysis were published in JAMA Oncology.
In the single-cohort, nonrandomized, prospective LAST study (ClinicalTrials.gov Identifier: NCT02269267), patients with chronic-phase CML who were enrolled at 14 centers were evaluated for outcomes after discontinuing TKIs. Included patients had well-controlled disease while treated with imatinib, dasatinib, nilotinib, or bosutinib.
One primary study endpoint was molecular recurrence, as determined by a BCR-ABL1 International Scale ratio of greater than 0.1%, reflecting a loss of major molecular response (MMR). This was evaluated by transcript analysis using real-time quantitative polymerase chain reaction (qPCR) or by droplet digital polymerase chain reaction (ddPCR) for samples with undetectable BCR-ABL1. Multiple patient-reported outcomes (PROs) were also among primary study endpoints.
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The median patient age was 60 years (range, 21-86) among 172 patients in this study. Patients had received a TKI for a median of 82.7 months (range, 36.1-199) by the start of enrollment. The median study follow-up occurred at 41.6 months.
A total of 171 patients were evaluable for molecular status. Of these, MMR was maintained in 65.5%, TFR had been reached by 60.8% of patients, and molecular recurrence was reported for 34.5% of patients, with a median time to recurrence of 4 months (range, 1.5-41.3).
BCR-ABL1 detectable by either qPCR or ddPCR upon TKI discontinuation was associated with molecular recurrence (hazard ratio [HR], 3.60 [95% CI, 1.99-6.50]; P <.001). When measured at 3 months after discontinuation, detectable BCR-ABL1 remained associated with molecular recurrence (HR, 5.86 [95% CI, 3.07-11.1]; P <.001). Patients with BCR-ABL1 detectable by either ddPCR or qPCR showed higher rates of recurrence, while patients with BCR-ABL1 undetectable by either method showed the lowest rate of recurrence.
Clinically meaningful improvements in multiple PROs were seen in patients who had reportedly reached TFR at 12 months. These included diarrhea (87.5% of patients), fatigue (80.4%), depression (34.8%), sleep disturbance (21.4%), and pain interference (4.5%). The study authors reported that resuming use of a TKI tended to worsen PROs.
“The LAST study demonstrates that patients with undetectable BCR-ABL1 by ddPCR had a very high chance of maintaining MMR, with modest improvements in PROs,” concluded the study authors in their report.
Disclosures: Some authors have declared affiliations with or received grant support from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.
Reference
Atallah E, Schiffer CA, Radich JP, et al. Assessment of outcomes after stopping tyrosine kinase inhibitors among patients with chronic myeloid leukemia: a nonrandomized clinical trial. JAMA Oncol. Published online November 12, 2020. doi:10.1001/jamaoncol.2020.5774
