Retrospective Study of Treatment Free Remission in Patients with Chronic Myeloid Leukaemia(CML) Treated at Tertiary Care Oncology Centre from India

Abstract

Background Tyrosine kinase inhibitors (TKI) have dramatically improved outcomes in Chronic Myeloid Leukemia(CML) patients, but lifelong TKI therapy can negatively impact patients' quality of life due to chronic adverse events. Treatment free remission(TFR) is now the new goal of CML therapy. Studies have shown this is feasible in developed countries. Literature on discontinuation of TKI therapy in resource limited countries such as India is scarce. The purpose of this study was to investigate whether some chronic myeloid leukemia patients with excellent and sustained molecular responses to tyrosine kinase inhibitor treatment can gradually de-escalate TKI therapy and stop therapy in Indian setting. Methods We included all patients above the age of 18years with diagnosis of CML in first Chronic Phase (CP) on TKI therapy of minimum 3 years duration with major molecular response (MMR i.e., <0.1% BCR-ABL1 transcript) of minimum of 2 years duration, enrolled for treatment free remission between January 2018 to December 2021. Starting dose of imatinib was 400mg once daily, dasatinib 100mg once daily and nilotinib 300mg twice a day. In this study the dose of these drugs was reduced by 25% every 6 months . This dose reduction was done with 2 monthly outpatient clinic visits and 2 monthly BCR-ABL1 quantitative PCR monitoring. Patients who maintained MMR during 6 months of dose de-escalation qualified for next level of dose de-escalation. Eventually treatment was stopped completely and monitoring continued. This was retrospective medical record based study done at a tertiary care centre in North India. Results Between Jan 2018 to Dec 2021, 29 patients were enrolled for dose de-escalation and treatment cessation. Among these 29 patients, 19 were on imatinib, 2 on dasatinib and 8 patients on nilotinib. Median age was 39 years( range 21 years to 67 years). Twelve patients were male and 17 female. Median duration of TKI therapy prior to de-escalation was 8 years (range 4years-14 years). Median duration of major molecular response prior to dose reduction was 6 years( range 3years-12 years). In our study 17 of 29 patients had an outcome, while 12 patients are still on de-escalation phase with maintained MMR and are not included in the outcome analysis. Eight patient had loss of MMR(47.05%), 6 while on dose de-escalation and 2 after cessation of TKI. All eight patients achieved MMR after re-initiation of the prior dose, out of these 6 patients had sustained MMR(>6months) at reduced TKI dosing compared to conventional dose. Nine patients (52.9%) have successfully stopped TKI for median duration of 11months (range 6 to 19 months). Conclusion TKI de-escalation was safe for most patients with excellent prior response to TKI therapy. This way of dose reduction , ensured motivation and commitment of patients by doing regular OPD follow ups and BCR-ABL1 PCR testing. In our study 52.9% patient could successfully maintain TFR at a median follow up of 11 months of stopping the drug. We also identified that a subgroup of patients(35.29%) who were unsuccessful in complete cessation of therapy but maintained their molecular response at reduce dose of TKI . These findings show that lower TKI doses might maintain molecular responses in these patients, implying that such patients could be overtreated with routine dosing. More studies of dose de-escalation are warranted.