Patients with chronic myeloid leukemia (CML) who achieved a longer deep molecular remission had higher rates of successful treatment-free remission (TFR) after discontinuing tyrosine kinase inhibitors (TKIs), according to research presented in a poster at the 2022 ASCO Annual Meeting.

Investigators analyzed outcomes in 284 patients with CML treated with TKIs between October 1999 and February 2017 who discontinued this therapy for any reason.

Patients who lost major molecular response (MMR) on any single test during follow-up were considered to have TFR failure. MMR was defined as a BCR-ABL1/ABL1 transcripts ratio of 0.1% or less based on real-time polymerase chain reaction; MR4 as a ratio of 0.01% or less by International Standard; and MR4.5 as a ratio of 0.0032% or less.


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The investigators performed univariate and multivariate analyses to identify factors associated with the loss of MMR.

Overall, the patients had a median age of 63 years at TKI discontinuation, and 51% were female. The large majority, 70%, had electively discontinued their TKI, whereas 24% had stopped therapy owing to adverse events; 32% had switched to at least 1 other TKI before discontinuation because of drug intolerance or resistance.

The median time from initiating a frontline TKI to discontinuation was 117 months (range, 16-242). The median duration of MR4 and MR4.5 before TKI discontinuation was 74 months (range, 2-207) and 64 months (range, 0-207), respectively.

At a median follow-up of 36 months (95% CI, 32-40) after TKI discontinuation, 53 patients (19%) had lost MMR, which resulted in a 5-year TFR rate of 79%. , Of those, 50 patients (94%) resumed TKI therapy, and all but 1 of 47 evaluable patients regained MMR, with 41 (88%) achieving MR4.5.

The estimated 5-year TFR rate was 91%, 76%, and 70% in patients who had maintained MR4.5 for 6 years and longer, for 5 to 6 years, and for less than 5 years, respectively (P <.0001). The estimated 5-year TFR rate was higher with MR4 for at least 5 years and MR4.5 for at least 5 years compared with MR4 for less than 5 years (92%, 87%, and 64%, respectively; P <.0001).

Patients who had continued their frontline TKI until the time of discontinuation had a 5-year TFR rate of 82% vs 75% and 72% for those who had switched to a second-line TKI or beyond owing to intolerance or resistance, respectively (P =.417). TFR rates did not vary significantly based on which TKI had been used frontline (P =.761).

Multivariate analysis showed that only durations in MR4 and in MR4.5 of at least 5 years before treatment discontinuation were associated with a lower risk of losing MMR, with hazard ratios of 0.37 (95% CI, 0.18-0.76; P =.007) and 0.20 (95% CI, 0.09-0.45; P <.0001), respectively.

The estimated 5-year TFR rate was 79% for patients who had monthly molecular monitoring after discontinuation compared with 85% for those who were monitored every 6 to 8 weeks (P =.263).

“Our findings suggest that achieving MR4 for 5 years [or more] was associated with a very high probability of maintaining TFR, and that less frequent molecular monitoring could be more cost-effective without any negative impact on outcomes,” the researchers wrote.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

Reference

Haddad FG, Jabbour E, Issa GC, et al. Treatment-free remission (TFR) in patients with chronic myeloid leukemia (CML) following the discontinuation of tyrosine kinase inhibitors. Presented at ASCO 2022; June 3-7, 2022. Abstract 7050.