Real-World Evidence Of Molecular Response To Tyrosine Kinase Inhibitors From China

Objective: Currently,there lacks available real-world clinical efficacy data on different strategies,such as comparing the efficacy of second-line nilotinib in Pts resistant or intolerant to imatinib.Meanwhile,when to apply the second generation of TKIs instead of the first generation of TKIs as well as their clinical efficacy hasn’t been defined.The present study was aimed to evaluate the applicability of recommendations of the European Leukemia Network guidelines for patients with chronic myeloid leukemia in chronic phrase in China then to explore these issues and optimize clinical therapy through evaluating molecular response at specific milestones according to ELN guidelines.Methods: According to ELN guidelines,We have enrolled 315 Pts from Multi-center in China from January2000 to December 2017 who were newly diagnosed with Chronic Myeloid Leukemia in chronic phrase.The study was descriptively analyzed and evaluated the different clinical efficacy of first-line imatinib-resistant or intolerant 175 patients who maintained imatinib and translated to second-line nilotinib.Result: At data collection,there are 175 patients were resistant or intolerant to first-line imatinib from 315 newly diagnosed CML-CP patients.During the observation period,of those resistant or intolerant to first-line imatinib,103 Pts remained on first-line imatinib treatment with no observed switch and 72 patients switched to second-line nilotinib.The rate of CCyR in nilotinib group was 94.44%,higher than that in imatinib group,67.96%(P < 0.0001),the rate of MMR in nilotinib group was79.17%,higher than that in imatinib group,58.25%(P =0.0038).85 Pts following“warning” response,71 Pts remained on first-line imatinib treatment and 14 Pts switched to nilotinib.Rates of CCyR at any time for Pts who remained on frontline imatinib with no observed switch following a prior "warning" response were 71.83%(51/71)and for Pts who switched to nilotinib were 92.86%(13/14)(P =0.1721);the rates of MMR at any time were59.15%(42/71)and 78.57%(11/14)accordingly(P =0.1705).78 Pts following “failure”response,32 Pts remained on first-line imatinib treatment and 46 Pts switched to nilotinib.Rates of CCyR at any time for Pts who remained on frontline imatinib with no observed switch following a prior "failure" response were 59.38%(19/32)and for Pts who switched to nilotinib were 93.48%(43/46)(P =0.0002);the rates of MMR at any time were56.25%(18/32)and 78.26%(36/46)(P =0.0383).Rates of CCyR and MMR at any time for Pts who switched to nilotinib following a prior "resistance" response were 100%.72 Pts resistant or intolerant to imatinib switched to nilotinib,34.72%(25/72)switched early(within 12 months)and 65.28%(47/72)switched later.Rates of CCyR for Pts who switched early and later were 96.0%(24/25)and 93.62%(44/47)(P = 0.6743).Rates of MMR for Pts who switched early and later were 84.0%(21/25)and 80.85%(38/47)(P = 0.7409).Sokal scores were analyzed in 94 patients with first-line CML-CP imatinib-resistant or intolerant patients,including 51 in the low-risk group of Sokal scores and 43 in the middle-high-risk group.The rates of CCyR at any time in the low-risk group of Sokal scores and the middle-high-risk group were 64.71%(33/51)and 44.19%(19/43),respectively(P = 0.0462);the rates of MMR at any time were 52.94%(27/51)and 25.58%(11/43),respectively(P =0.0071).39 of them switched to second-line nilotinib,and the rates of CCyR at any time in the low-risk group of Sokal scores were 82.35%(42/51)and in the middle-high-risk group were 76.74%(33/43),respectively(P =0.4999);the rates of MMR at any time were 74.51%(38/51)and 60.47%(26/43),respectively(P = 0.1456).The rates of CCyR at any time in frontline imatinib and nilotinib were 72.03%(206/286)and 82.8%(29/29)(P =0.0010),with a median follow-up time of 7 months and 3 months,respectively;the rates of MMR at any time were 62.59%(179/286)and 86.21%(25/29)(P = 0.0112),with a medianfollow-up time of 8 months and 3 months,respectively.There were 224 Pts who following a prior "failure" response then switched to nilotinib(including 71 Pts achieved warning response and 107 achieved optimal response who maintained frontline imatinib treatment and 46 achieved failure response who switched to second-line nilotinib).Compared with first-line nilotinib,the rates of CCyR at any time were 90.18%(202/224)and 100%(29/29)(P= 0.0874),the rates of MMR at any time were 81.70%(183/224)and 86.21%(25/29),respectively(P = 0.5501).Most of the adverse reactions of nilotinib were slightly and tolerable,and patient compliance was better.Conclusions: According to ELN recommendations for the management of patients with newly diagnosed CML-CP in China,the clinical efficacy of Pts who resistant or intolerant to first-line imatinib were significantly more effective in switching to second-line nilotinib,especially in the medium and high risk Sokal group and the “failed” patients.Patients who resistant or intolerant to imatinib translated to second-line nilotinib can reach similar efficacy as the frontline nilotinib and better tolerated.Patients following a prior "warning" response can remain on first-line imatinib treatment,some patients still attain CCyR and MMR.Whereas progressed to failure,the second-line nilotinib treatment should be converted as soon as possible,and the time of transmitting has no significant effect on the post-conversion effect.Overall,the results support the use of ELN2013 recommendations to guide TKI management.