Recent studies showed that tyrosine kinase inhibitors (TKI) treatment could be safely discontinued in a selected group of chronic phase (CP) chronic myeloid leukemia (CML) patients that achieved deep molecular response (DMR), making treatment-free remission (TFR) a new goal of therapy. The discontinuation of treatment in patients with sustained molecular response to MR4 or MR4.5, a practice that has been performed in other countries is not feasible in Brazil outside clinical trials because of the lack of coverage for performing RQ-PCR as recommended by the international guidelines. For all these aspects, it seemed essential to us to analyze the financial impact of TKI discontinuation, following strict monitoring criteria, and perform a projection of economic costs in a population of CML patients treated in first-line with imatinib eligible for discontinuation.

To demonstrate the feasibility of coverage of Q-PCR to perform discontinuation of imatinib treatment on eligible patients [ treatment free-response (TFR)] in Brazil based on the financial impact.

From 2020 -2021, 20 eligible patients from a single private institution in Brazil were invited to participate in a single-arm trial of Imatinib discontinuation (DIP). After discontinuation, patients were monitored by RT- PCR monthly in the first year, every two months in the second year, and every three months after the third year. Criteria for Imatinib re-initiation were the same of the Euro-Ski trial. Considering that US$ 1.00 are R$ 5.3 (Brazilian currency- March /2022) for Branded Imatinib – 400 mg/d, the monthly cost has been estimated at R$ 16,933.90 or US$ 3,95.07 and the generic imatinib- 400mg/d monthly R$ 13,048.90 or US$ 2,462.05 (CEMED- March/2022). The unitary value for the Q-PCR exam has been estimated, with a large price range at R$ 1,311.25 (R$790.00 to R$ 2,159.00) or US$ 247.40.

Of 26 patients, 20 consent to discontinuation of imatinib. Twelve patients (60%) presented MR4. Median time diagnosis to discontinuation of imatinib 8.5 (4.6-15.5) years. Twelve (60%) patients sustained TFR. During the follow-up, 244 RQ-PCR were performed. The cumulative time without treatment was 224.5 months. The costs with Q-PCR were R$ 319,945.00 or US$ 60,366.98 (244 exams during follow-up (median time 14,4 months). The average time of months without treatment was 224.5 months. The cost of treatment without discontinuation would be R$ 4,131,871.60 or US$ 779,598.41 (Branded Imatinib) or R$ 2,929,478.05 or US$ 552,731.70 (imatinib copies). The saving on median time of follow-up (14.4 months) were R$ 3,811,926.60 or US$ 719,231.43 (Branded Imatinib) or R$ 2,609,533.05 or US$ 492,364.72 (imatinib copies).

Considering the methodology of Cost-Utility, the saving resulting from the discontinuation of treatment for 20 patients for 14.4 months despite the loss of MR of 40 % of patients were R$ 3,811,926.60 or US$ 719,231.43 (Branded Imatinib) or R$ 2,609,533.05 or US$ 492,364.72 (imatinib copies). The results show that if Q-PCR tests were available in clinical practice, within pre-established protocols, there would be equalization and adequacy with the international monitoring guidelines, and discontinuation protocols could be feasible in clinical practice.

The possibility of discontinuation would have a huge financial impact on the Brazilian Health System, resulting in the economic viability of treating hundreds of patients and performing thousands of Q-PCR exams, creating a rational and balanced model of clinical efficacy coupled with basic sustainability premises of modern oncology.