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. 2019 Jan 3;12(1):1.
doi: 10.1186/s13045-018-0686-1.

Tyrosine kinase inhibitor discontinuation in patients with chronic myeloid leukemia: a single-institution experience

Kamal Chamoun  1 , Hagop Kantarjian  1 , Rami Atallah  1 , Graciela Nogueras Gonzalez  2 , Ghayas C Issa  1 , Mary Beth Rios  1 , Guillermo Garcia-Manero  1 , Gautam Borthakur  1 , Farhad Ravandi  1 , Nitin Jain  1 , Naval Daver  1 , Marina Konopleva  1 , Courtney D DiNardo  1 , Tapan Kadia  1 , Naveen Pemmaraju  1 , Elias Jabbour  1 , Jorge Cortes  3
Affiliations

Tyrosine kinase inhibitor discontinuation in patients with chronic myeloid leukemia: a single-institution experience

Kamal Chamoun et al. J Hematol Oncol. .

Abstract

Background: Patients with CML treated with TKI can have a life expectancy comparable to that of the general population. Due to the extended duration of TKI administration, treatment discontinuation has been increasingly sought.

Methods: Medical records of 100 patients with CML who were in MR4.5 and discontinued their TKI outside clinical trials were reviewed.

Results: After a median follow-up of 30 months (range, 5-112 months) after discontinuation, 35% and 17% lost MR4.5 and major molecular response (MMR), respectively. Only six patients lost MMR 12 months or more after discontinuation. Loss of MR4.5 was observed in 29% and 7% of patients with sustained MR4.5 duration of more than 2 and 6 years before discontinuation, respectively. By univariate analysis, there was a higher risk of loss of MR4.5 for patients who were treated for less than 87 months, received second or subsequent line TKI, never received interferon, or those with sustained MR4.5 for less than 6 years. By multivariate analysis, sustained MR4.5 for 6 years or more was the only significant predictor for durable response. Overall, 30% of patients who discontinued while in MR4.5 were retreated with 93% regaining MR4.5 at a median of 5 months.

Conclusion: These results demonstrate that under proper conditions, treatment discontinuation is feasible outside of clinical trial setting. MR4.5 duration of 6 years or more before discontinuation is associated with very low risk of loss of MR4.5.

Keywords: CML; MR4.5; TKI discontinuation.

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Conflict of interest statement

Authors’ information

None.

Ethics approval and consent to participate

This research was approved by the institutional review board (IRB) at MD Anderson Cancer Center, Houston, Texas, USA, and a waiver for informed consent was obtained.

Consent for publication

Not applicable (waiver of informed consent granted by IRB).

Competing interests

Jorge Cortes has received research support (for the Institution) from BMS, Novartis, Pfizer, and Takeda. All other authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Kaplan Meier curve of percentage of sustained MR4.5 after discontinuation. a In the overall population, 2-year estimate: 64%, 95% CI [53, 73]. b According to duration of TKI treatment (< 87 months vs ≥ 87 months). c According to type of frontline treatment (TKI vs interferon). d According to type of frontline and only TKI (imatinib vs dasatinib vs nilotinib). e According to lines of treatment (first line vs two or more line). f According to duration to achieve MR4.5 (< 17 months vs ≥ 17 months). g According to sustained MR4.5 duration before discontinuation (< 72 months vs ≥ 72 months). h According to reason of discontinuation (elective vs adverse events)
Fig. 2
Fig. 2
Kaplan Meier curve of percentage of sustained MMR after discontinuation. a In the overall population, two-year estimate: 82%, 95% CI [72, 89]. b Excluding patients who resumed therapy before losing MMR, 2-year estimate: 79%, 95% CI [67, 87]
Fig. 3
Fig. 3
Kaplan Meier curve of treatment-free remission. a In the overall population, treatment-free remission at 2 years: 70%, 95% CI [59, 79]. b Censoring patients who resumed therapy before losing MMR, treatment-free remission at 2 years: 83%, 95% CI [73, 90]
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