CML paper summary #8 - April 2026 - Treatment-free remission in low- and middle-income countries

Treatment-free remission in chronic myeloid leukemia in low- and middle-income countries
Annamalay A, et al. Treatment-free remission in chronic myeloid leukemia [letter]. 
N Engl J Med. 2026. doi:10.1056/NEJMc2518028

Summary

This letter to the editor of the New England Journal of Medicine reports outcomes from the first structured, multi-country treatment-free remission (TFR) program implemented specifically in low- and middle-income countries (LMICs). Coordinated by the Max Foundation across eight countries, the program enrolled 95 patients with chronic phase CML who had received imatinib for a mean of 15 years and met stringent eligibility criteria for deep molecular response (DMR). At a median follow-up of 544 days, 79% of patients remained in TFR, with a molecular relapse rate of 21%, comparing favourably with data from high income country (HIC) cohorts. Critically, monitoring adherence was high and implementation strategies successfully addressed the structural barriers that have historically made TFR inaccessible in resource limited settings. This study provides compelling evidence that TFR is achievable in LMICs when access to diagnostics, physician training, and patient support are systematically addressed.

Key points for clinicians 

  • TFR is feasible in LMICs with appropriate structural support, including access to molecular diagnostics and consistent follow-up
  • Conservative eligibility criteria (at least 10 years of imatinib, sustained DMR on two annual tests) were associated with a 79% TFR success rate.
  • Molecular relapse occurred in 21% of patients, substantially lower than the approximately 40% reported in comparable HIC meta-analyses.
  • Among patients who relapsed and restarted imatinib, 14 of 16 with follow-up data regained major molecular response (MMR).
  • Monitoring adherence was high: only 6% of patients missed a scheduled visit, and 92% completed testing within 15 days of their scheduled date.
  • GeneXpert platforms and validated local laboratory methods can support BCR::ABL1 monitoring in resource limited settings.
  • Targeted patient support, including transportation assistance, patient navigation, and support groups, was provided to approximately 20% of participants and contributed to program success.

Introduction

TKIs have transformed CML into a chronic, manageable condition. In HIC settings, approximately half of patients who achieve a sustained DMR can successfully discontinue TKI therapy and maintain TFR. However, this therapeutic goal has remained largely out of reach in LMICs due to three interconnected barriers: limited and often precarious TKI access, inadequate molecular diagnostic infrastructure, and inconsistent patient follow-up. As a result, the global benefits of TFR have been concentrated in wealthier health systems.

The Max Foundation, a global non-profit supporting CML care in resource limited settings, designed and implemented a structured TFR program to address these barriers directly, generating the first prospective multi-country dataset on TFR outcomes in LMICs.

Methods

This was a prospective, protocol-driven TFR program conducted by the Max Foundation from August 2021 through November 2025 across eight countries: Armenia, the Dominican Republic, El Salvador, Ethiopia, Honduras, India, Kenya, and Paraguay.

Eligibility criteria were intentionally conservative and required:

  • Chronic phase CML treated with imatinib for at least 10 years
  • No prior TKI resistance
  • Sustained DMR (BCR::ABL1 ≤0.0032% IS) for at least 12 months, confirmed on two consecutive annual tests

After written informed consent, imatinib was discontinued and patients entered the monitoring protocol: monthly BCR::ABL1 testing for 6 months, then every 3 months to 24 months, then every 6 months thereafter. Loss of MMR (BCR::ABL1 >0.1%) triggered reinitiation of imatinib at the prior dose.

Implementation strategies to address LMIC specific barriers included:

  • BCR::ABL1 testing via GeneXpert platforms or other validated local methods
  • Full coverage of all testing costs by the program
  • At least two laboratories per country to mitigate equipment or supply interruptions
  • Physician training on TFR protocols
  • Patient support interventions (transportation assistance, patient navigation, and support groups) for approximately 20% of participants

Key findings

Patient characteristics

A total of 95 patients entered TFR. The median age at discontinuation was 53 years (range 22 to 83) and the mean duration of prior imatinib therapy was 15 years. Before discontinuation, 79% of patients had undetectable BCR::ABL1 on both qualifying tests. All 95 patients had a minimum of 6 months of follow-up, with a median follow-up of 544 days.

TFR outcomes

Molecular relapse occurred in 20 of 95 patients (21%). The median time to relapse was 103.5 days (range 26 to 1,121), and 65% of relapses occurred within the first 6 months after discontinuation. At last follow-up, 75 patients (79%) remained in TFR.

Among the 20 patients who relapsed and restarted imatinib, 16 had at least one follow-up molecular test, and 14 (88%) had regained MMR.

Monitoring adherence

Adherence to the monitoring protocol was high. Only 6% of patients missed an expected monitoring visit, and 92% completed testing within 15 days of their scheduled date.

Comparison with HIC data

The 21% molecular relapse rate in this cohort compares very favourably with meta-analyses of TFR studies conducted primarily in HICs, which have reported molecular relapse in approximately 40% of patients within the first year after TKI discontinuation. The authors attribute part of this difference to the more conservative eligibility criteria, particularly the requirement for at least 10 years of prior TKI therapy, which aligns with emerging evidence that longer treatment duration predicts higher TFR success.

Conclusions

This study demonstrates for the first time, across a multi-country LMIC cohort, that TFR is not only scientifically feasible but practically achievable when structural barriers are systematically addressed. The high rate of sustained TFR, excellent monitoring adherence, and favorable outcomes after relapse all point to a well-designed program delivering meaningful results for patients in settings where such outcomes were previously considered unattainable.

The authors argue that expanding models of this kind represents a concrete pathway to reducing global inequities in CML care. While the conservative eligibility criteria and the program's reliance on external funding from the Max Foundation must be acknowledged as context dependent factors, the operational lessons from this study, particularly around diagnostic access, physician training, and patient centered support, are broadly applicable and scalable.

For clinicians and health systems working in LMICs, this paper offers both an evidence base and a practical blueprint. For the wider CML community, it is a reminder that the aspiration of TFR should not remain the exclusive domain of patients in high income settings.

Link to full abstract