Outcomes After Discontinuation of Tyrosine Kinase Inhibitor Therapy for CML
Posted: Tuesday, December 1, 2020
Ehab Atallah, MD, of the Medical College of Wisconsin, Milwaukee, and colleagues conducted a multicenter study to evaluate molecular recurrence and patient-reported outcomes after discontinuation of tyrosine kinase inhibitor therapy in those with chronic-phase chronic myeloid leukemia (CML). The results of the LAST trial were published in JAMA Oncology.
“Our results provide important new information to inform the discussion between patients with CML and clinicians about the risks and benefits of tyrosine kinase inhibitor discontinuation and the potential to assess tyrosine kinase inhibitor cessation more accurately,” the investigators commented.
The study enrolled a total of 172 patients whose disease was well controlled after treatment with imatinib (59.3%), nilotinib (22.7%), dasatinib (15.7%), or bosutinib (2.3%). The molecular analysis focused on 171 evaluable patients. Molecular recurrence was defined as the loss of major molecular response (BCR-ABL1 transcript levels > 0.1%). The investigators performed droplet digital polymerase chain reaction (PCR) on samples with BCR-ABL1 transcripts undetectable by standard real-time quantitative PCR.
According to the investigators, 65.5% of patients remained in major molecular response, and 60.8% achieved treatment-free remission. BCR-ABL1 transcripts undetectable by either method seemed to be independently associated with molecular recurrence at the time of treatment discontinuation (hazard ratio = 3.60; P < .001) and after 3 months (hazard ratio = 5.86; P < .001). One-half of patients with BCR-ABL1 transcripts detectable by real-time quantitative PCR (50.0%) experienced a molecular recurrence. Molecular recurrences occurred in 64.3% of patients with BCR-ABL1 transcripts undetectable by real-time quantitative PCR but detectable by droplet digital PCR and in 10.3% of those with BCR-ABL1 transcripts undetectable by both methods.
Clinically meaningful improvements in fatigue (80.4%), depression (34.8%), diarrhea (87.5%), sleep disturbance (21.4%), and pain interference (4.5%) were observed in patients who achieved treatment-free remission at 12 months. Resumption of treatment seemed to result in worsened patient-reported outcomes.
Disclosure: For full disclosures of the study authors, visit jamanetwork.com.