Feasibility of treatment-free remission with generic imatinib

Abstract

Background & objectives: Both innovator and generic imatinib are approved for the treatment of Chronic Myeloid Leukaemia-Chronic phase (CML-CP). Currently, there are no studies on the feasibility of treatment-free remission (TFR) with generic imatinib. This study attempted to determine the feasibility and efficacy of TFR in patients on generic Imatinib. Methods: In this single-centre prospective Generic Imatinib-Free Trial-in-CML-CP study, twenty six patients on generic imatinib for ≥3 yr and in sustained deep molecular response (BCR ABL IS ≤0.01% for more than two years) were included. After treatment discontinuation, patients were monitored with complete blood count and BCR ABL IS by real-time quantitative PCR monthly for one year and three monthly thereafter. Generic imatinib was restarted at single documented loss of major molecular response (BCR ABL IS >0.1%). Results: At a median follow up of 33 months (interquartile range 18.7-35), 42.3 per cent patients (n=11) continued to be in TFR. Estimated TFR at one year was 44 per cent. All patients restarted on generic imatinib regained major molecular response. On multivariate analysis, attainment of molecularly undetectable leukaemia (>MR 5 ) prior to TFR was predictive of TFR [ P =0.022, HR 0.284 (0.096-0.837)]. Interpretation & conclusions: The study adds to the growing literature that generic imatinib is effective and can be safely discontinued in CML-CP patients who are in deep molecular remission.

Treatment-free remission after discontinuation of tyrosine kinase inhibitors in patients with chronic myeloid leukemia in the chronic phase: a systematic review and meta-analysis

“…Our study showed a 12-month overall mean TFR rate of 60% [95CI:0.56-0.63] and a 24-month overall mean TFR rate of 55% [95CI:0.52-0.59], indicating that more than half of the CML-CP patients were able to maintain TFR two years after TKI discontinuation. Our subgroup analysis showed that better TFR was associated with prior interferon therapy (12months: P < 0.001,24months: P = 0.006), and molecular response depth MR5.0 (12months:P = 0.005,24months: P = 0.02), which is in line with the ndings of previous trials [23,33,35] , although this analysis exists heterogeneity. According to the previous study [15] , the duration of DMR and TKI therapy before discontinuation were found to be associated with TFR.…”

“…A total of 19 trials [23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41] involving 2336 patients were included in this meta-analysis. Eight trials have investigated the probability of TFR after imatinib treatment [23,25,32,36,[39][40][41] , four trials have investigated the probability of TFR after dasatinib treatment [24,[28][29][30] , three trials have investigated the probability of TFR after nilotinib treatment [26,34,37] , and the remaining four trials have investigated the probability of TFR after treatment with different TKIs [27,31,33,38] . There were no clinical trials related to the discontinuation of umatinib, third-generation TKIs, etc., and only the LAST, GIMEMA CML0307 trial had 7 patients on bosutinib [26,27] .…”

Molecular BCR::ABL1 Quantification and ABL1 Mutation Detection as Essential Tools for the Clinical Management of Chronic Myeloid Leukemia Patients: Results from a Brazilian Single-Center Study

“…Eighteen patients remained in continuous TFR, and no patient progressed to the advanced phase, suggesting long-term safety and remarkable stability of response after imatinib discontinuation in appropriately selected CML patients [ 57 ]. A recent report by Goni et al recruited 26 CML patients on generic imatinib for ≥3 years and in sustained deep molecular response, where the median follow-up was 33 months, and 42.3% continued to be in TFR, with all patients who restarted on generic imatinib regaining a major molecular response [ 58 ]. A similar approach in 190 CML Chinese patients enrolled in the TFR protocol showed a success rate of 76.9% (95% CI, 70.2–82.4%), 68.8% (95% CI, 61.3–75.2%), and 65.5% (95% CI, 57.4–72.5%) at 6, 12, and 24 months after stopping TKI, and 98.2% of patients who needed to restart TKI treatment quickly achieved MMR [ 59 ].…”