Real-World Data Support TKI Discontinuation After CP-CML Remission

New real-world data suggest that discontinuation of tyrosine kinase inhibitor (TKI) therapy in patients with chronic-phase chronic myeloid leukemia (CP-CML) is safe and that most patients will experience treatment-free remission (TFR).

The report was published in Clinical Lymphoma, Myeloma, and Leukemia.¹

TKIs have dramatically improved the management of CML, allowing patients to achieve life expectancies similar to the general population, wrote corresponding author Aamer Aleem, MBBS, of Saudi Arabia’s King Saud University, and colleagues. Yet, they said, the long-term use of TKI therapy can lead to significant toxicity and other burdens.

The new findings join other studies examining the impacts of therapy discontinuation after patients achieve a deep molecular response to therapy. | Image Credit: © Vitalii Vodolazskyi - stock.adobe.com

“There is increasing evidence that second- and third-generation TKIs can potentially cause significant morbidity and mortality,” they wrote. “Moreover, the financial burden of lifelong TKI therapy can be substantial, both for patients and the health care system, and discontinuation of treatment may save significant money.”

Those factors have led many to examine the impacts of therapy discontinuation after patients achieve a deep molecular response to therapy. Aleem and colleagues said the evidence so far has been encouraging. For instance, long-term data published in 2017 showed that cessation of imatinib (Gleevec) in patients with CML who had undetectable minimal residual disease (MRD) following therapy led to long-term molecular recurrence-free survival in 38% of patients.² Although a majority of patients experienced recurrence and restarted therapy, almost all were able to once again achieve undetectable MRD after restarting therapy.

Aleem and colleagues said subsequent studies have affirmed that between 40% to 60% of patients are able to achieve durable TFR after discontinuing TKIs.¹ However, they added that most of the data to date have been from clinical trial settings. Real-world data remain relatively scarce, they said, and are particularly limited with regard to patients from the Middle East and low-income countries.

The investigators decided to retrospectively analyze patients at 3 Saudi medical centers who had been diagnosed with CP-CML, had received TKI therapy for at least 24 months following achievement of a deep molecular response, and attempted to discontinue therapy. The 55 patients included in the analysis were aged 16 to 74 years at diagnosis. The majority of patients (35) were female. Almost all of the patients in the study (n = 48) received imatinib as first-line therapy, and 29 patients were receiving imatinib at the time of discontinuation, the authors said. The patients had been on TKI therapy for a median time of 66 months following achievement of a deep molecular response, the investigators said, and the patients had been diagnosed a median of 86 months prior to discontinuation of TKI therapy.

Aleem and colleagues found that, at a median follow-up of 34 months, just 15 patients (27.3%) had experienced a relapse. The median time to relapse was 5 months, and all but 3 patients relapsed within the first 6 months.

“The results of the current study demonstrate that TKI discontinuation is feasible and safe in routine clinical practice and TFR can be achieved in more than two-thirds of carefully selected patients,” they wrote.

In all cases, patients who relapsed were able to achieve a major molecular response once TKI therapy was restarted, and no patients progressed to advanced-phase disease, the authors reported.

Aleem and colleagues said their findings about the timing of relapses align with previously published studies, which have generally shown that most patients who relapse will relapse within the first year after discontinuation. However, they noted that 1 patient in their study relapsed 38 months after discontinuation.

“The possibility of late relapses in some patients mandates long-term surveillance and follow-up of these patients,” they wrote.

Overall, though, the investigators said their data support the concept of TKI discontinuation in certain patients who achieve a deep molecular response to therapy. They said their study and others suggest that a longer duration of TKI therapy might improve the odds of TFR after discontinuation.

References

1. Aleem A, Shaheen NA, Algahtani F, et al. Discontinuation of tyrosine kinase inhibitor therapy and treatment free remission (TFR) in chronic myeloid leukemia: successful achievement of TFR in more than two-third of patients in a real-world practice. Clin Lymphoma Myeloma Leuk. Published online August 24, 2024. doi:10.1016/j.clml.2024.08.006
2. ‌Etienne G, Guilhot J, Rea D, et al. Long-term follow-up of the French Stop Imatinib (STIM1) study in patients with chronic myeloid leukemia. J Clin Oncol. 2017;35(3):298-305. doi:10.1200/JCO.2016.68.2914