Successful Treatment-Free Remission in Low- and Middle-Income Countries

Introduction Discontinuation of tyrosine kinase inhibitors (TKIs) is feasible in a subset of chronic myeloid leukemia (CML) patients who have maintained a deep molecular response (MR) for ≥2 years. Numerous TKI discontinuation trials from high-income settings show that ~50% of patients relapse after discontinuing TKIs and need to restart treatment. However, most patients with CML worldwide are from low- and middle-income countries LMIC where TKI access and molecular testing make routine care and attempts of treatment-free remission (TFR) problematic. The successful implementation of TFR in LMICs would benefit both CML patients as well as the health economics of each country. This analysis describes the experience of attempting TKI discontinuation in the LMIC setting. Methods The Max Foundation's TFR Support Program provides financial and wrap-around support for patients attempting TFR in LMICs. The program operates in countries where The Max Foundation has existing partner institutions and physicians, imatinib and second line TKIs are available, and there is ≥1 reliable method of quantitative RT-PCR testing for BCR::ABL1. Eligible patients were >18 years old, diagnosed with chronic phase CML and treated with imatinib for ≥10 years with no history of resistance, and had a BCR-ABL level MR 4.5 or better (≤0.0032%) for ≥12 months (m) as demonstrated by 2 RT-PCR tests. Patients who consented were enrolled in the program and monitored by their treating physician. Upon starting TFR, patients' BCR::ABL1 levels were tested monthly for the first 6 m, then every 3 m for the following 6 m, then every 6 m. Patients who relapsed (BCR::ABL1 loss of MR 3 or >0.1%) after beginning TFR restarted imatinib and were tested approximately every 1-3 m until they achieved MR 3. We conducted a retrospective analysis on the outcomes of patients enrolled in The Max Foundation's TFR Support Program to better understand TFR outcomes in an LMIC setting. Results The molecular results pre- and post-TKI discontinuation are shown in Figure 1. In total, 39 patients from sites in 5 countries (Armenia, Honduras, India, Kenya, and Paraguay) were followed by 8 program physicians. The mean age of the patients was 51 years (range, 22-77), with 22 females and 17 males. Patients had been on imatinib for an average of 15 years (range, 10-20). At time of discontinuation, all but 1 patient was on 400 mg/day of imatinib (1 treated at 300 mg/day). Thirty-two patients had undetectable BCR::ABL1 for both