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  • 1
    In: Leukemia, Springer Science and Business Media LLC, Vol. 35, No. 8 ( 2021-08), p. 2332-2345
    Type of Medium: Online Resource
    ISSN: 0887-6924 , 1476-5551
    RVK:
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2008023-2
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  • 2
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 32, No. 25 ( 2014-09-01), p. 2823-2825
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2014
    detail.hit.zdb_id: 2005181-5
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  • 3
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 32, No. 5 ( 2014-02-10), p. 424-430
    Abstract: More than half of patients with chronic-phase chronic myelogenous leukemia (CP-CML) in complete molecular response (CMR) experience molecular relapse after imatinib discontinuation. We investigated loss of major molecular response (MMR) as a criterion for resuming therapy. Patients and Methods A multicenter observational study (A-STIM [According to Stop Imatinib]) evaluating MMR persistence was conducted in 80 patients with CP-CML who had stopped imatinib after prolonged CMR. Results Median time from imatinib initiation to discontinuation was 79 months (range, 30 to 145 months);median duration of CMR before imatinib discontinuation was 41 months (range, 24 to 96 months); median follow-up after discontinuation was 31 months (range, 8 to 92 months). Twenty-nine patients (36%) lost MMR after a median of 4 months off therapy (range, 2 to 17 months). Cumulative incidence of MMR loss was estimated as 35% (95% CI, 25% to 46%) at 12 months and 36% (95% CI, 26% to 47%) at 24 months, whereas probability of losing CMR was higher. Fluctuation of BCR-ABL transcript levels below the MMR threshold (≥ two consecutive positive values) was observed in 31% of patients after imatinib discontinuation. Treatment-free remission was estimated as 64% (95% CI, 54% to 75%) at 12 and 24 months and 61% (95% CI, 51% to 73%) at 36 months. Median to time to second CMR was estimated as 7.3 months in re-treated patients. Conclusion Loss of MMR is a practical and safe criterion for restarting therapy in patients with CML with prolonged CMR.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2014
    detail.hit.zdb_id: 2005181-5
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  • 4
    In: Journal of the National Cancer Institute, Oxford University Press (OUP), Vol. 108, No. 7 ( 2016-07), p. djw003-
    Type of Medium: Online Resource
    ISSN: 0027-8874 , 1460-2105
    RVK:
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2016
    detail.hit.zdb_id: 2992-0
    detail.hit.zdb_id: 1465951-7
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  • 5
    In: Blood, American Society of Hematology, Vol. 134, No. Supplement_1 ( 2019-11-13), p. 30-30
    Abstract: Background : Providing achievement and sustainability of deep molecular responses (DMR), patients (pts) taking tyrosine kinase inhibitors (TKI) against CML may discontinue therapy. The STOP 2G-TKI observational study showed that dasatinib and nilotinib could be safely stopped and prior suboptimal response or resistance to imatinib was an adverse prognostic factor for treatment-free remission (TFR). We present updated results with a specific focus on the risk of relapse using post-baseline information during follow-up. Methods : Adult CML pts treated with dasatinib or nilotinib without a history of allogeneic stem cell transplantation (ASCT) or progression to advanced phase stopped TKI provided that: (1) BCR-ABL transcripts were of the major type, (2) total TKI treatment duration was ≥36 months, (3) uMR4.5 had been achieved and maintained for ≥24 months (undetectable BCR-ABL with ≥32000 copies of ABL). Relapse was defined by loss of major molecular response (MMR: BCR-ABL IS & gt;0.1%) on a single occasion and triggered TKI reintroduction. The primary objective was TFR at 12 months. After TKI discontinuation, BCR-ABL transcripts were monitored monthly during the first 6-12 months, every 3 months during the 2nd year and then every 3-6 months. Data as of July 1, 2019 are reported in 104 pts (median follow-up 55 months (range: 6-70)). Results: Median age at inclusion was 56 years (range: 21-82) and 65.4% of pts were female. Sokal risk score was low in 49%, intermediate in 31%, high in 16% and unknown in 4%. 2G-TKIs were given after imatinib intolerance in 47% of pts, suboptimal response or resistance to imatinib in 22%, lack of DMR on imatinib in 3% and as 1st line treatment in 28%. Median duration of TKI, 2G-TKI and uMR4.5 was 74 months (range: 36-163), 49 months (range: 19-112) and 31 months (range: 24-72), respectively. Overall, 43 pts (41%) lost MMR within a median time of 5 months (range: 1-59). Overall 60-month TFR was 56% (95% CI, 45.8-66.3) but TFR probabilities increased up to 64% (95% CI: 53.3-74.8), 76.7% (95% CI, 65.9-87.5), 86.2% (95% CI; 76.3-96.2), and 92.1% (95% CI: 83.4-100) for pts still in MMR at 3, 6, 12 and 18 months, respectively (Figure 1). Prior suboptimal response or resistance to TKI was confirmed as the strongest adverse baseline prognostic factor with a 60-month TFR rate of 29.8% (95% CI; 10.8-48.7) (median TFR 12 months) versus 63.6% (95% CI; 52.1-75.2) (median not reached) in pts without such history (logrank p=0.0012). This was explained by significantly higher risk of early relapses (within 6 months but not later) in pts with prior suboptimal response or resistance to TKI (cumulative incidence of relapses by 6 months 47.8% (95% CI; 31.2-73.2) versus 20.9 (95% CI; 13.7-32) in other pts (p=0.00879)). Landmark analyses at specific time points were performed to study the prognostic value of molecular responses categories after TKI discontinuation. All pts in MMR but not deeper at 3 months relapsed by month 9 (median time to relapse 4 months) while pts in ≥MR4 (BCR-ABL IS ≤0.01%) had 12- and 60-months probabilities of 86.8% (95% CI; 79.1-94.4) and 74.9% (95% CI: 64-85.7), respectively (logrank p & lt;10-4). All pts but 1 in MMR but not deeper at 6 months relapsed (median time to relapse 12 months) while pts in ≥MR4 had 12- and 60-months probabilities of 95% (95% CI; 89.6-100) and 87.5% (95% CI: 78.7-96.2), respectively (logrank p & lt;10-4). Forty three pts restarted treatment including 1 who lost MR4.5 but not MMR and 42 who lost MMR. When treatment was reintroduced, 42 pts were in CHR and all regained MMR after a median time of 3 months (range: 1-11). The remaining pt lost MMR but not CHR 5 month after 1st line nilotinib cessation and was found in sudden myeloid blast crisis at the month 6 TKI reintroduction visit. No BCR-ABL mutation was found but an inversion of chromosome 3 at karyotyping analysis. The pt underwent ASCT after chemotherapy + ponatinib and is alive in remission 29 months later. Conclusion: 2G-TKI may be successfully stopped in CML pts with long-lasting MR4.5. Those without a history of suboptimal response or resistance have greatest chances of success. Sudden blast crisis is rare but unpredictable. Post-TKI discontinuation estimates of TFR change overtime. Together with that of molecular response type at specific time points, they represent important dynamic prognostic measures of outcome. They may also help individualizing molecular monitoring programs after TKI cessation. Disclosures Rea: Incyte Biosciences: Honoraria; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Honoraria; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees. Nicolini:Sun Pharma Ltd: Consultancy; Incyte Biosciences: Honoraria, Research Funding, Speakers Bureau; Novartis: Research Funding, Speakers Bureau. Rousselot:Pfizer: Research Funding; Incyte: Research Funding. Etienne:Pfizer: Honoraria, Speakers Bureau; Incyte Biosciences: Honoraria, Speakers Bureau; BMS: Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria, Speakers Bureau. Guerci:INCYTE: Consultancy, Honoraria. Legros:Pfizer: Honoraria, Research Funding; BMS: Honoraria; Novartis: Honoraria; Incyte Biosciences: Honoraria, Research Funding. Coiteux:Pfizer: Honoraria; BMS: Honoraria; Novartis: Consultancy, Honoraria; Incyte: Consultancy, Honoraria. Mahon:Pfizer: Honoraria, Speakers Bureau; BMS: Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria, Speakers Bureau; Incyte Biosciences: Honoraria, Speakers Bureau.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2019
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    detail.hit.zdb_id: 80069-7
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  • 6
    In: New England Journal of Medicine, Massachusetts Medical Society, Vol. 337, No. 4 ( 1997-07-24), p. 223-229
    Type of Medium: Online Resource
    ISSN: 0028-4793 , 1533-4406
    RVK:
    Language: English
    Publisher: Massachusetts Medical Society
    Publication Date: 1997
    detail.hit.zdb_id: 1468837-2
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  • 7
    In: Blood, American Society of Hematology, Vol. 124, No. 21 ( 2014-12-06), p. 1793-1793
    Abstract: Although they produce high rate of molecular response second generation tyrosine kinase inhibitors or imatinib cannot eradicate CML primitive progenitors. Interferon has been shown to modulate gene expression, inhibits leukemic cell growth and induces an immunomodulatory response. In vitro studies support the use of combination of IM plus interferon. We designed a phase III randomised multicenter open-label prospective trial comparing IM 400 mg/d (n=223) with 3 experimental arms: IM 600 mg/d (n=171), IM 400 mg/d combined to s/c Peg-IFN2a (90 µg/wk) (n=221) and IM 400 mg/d combined to s/c Ara-C, (20 mg/m2/d, d15-28 of 28-day cycles)(n=172). Pts were allocated at a 1.1.1.1 ratio, stratified by Sokal risk groups. Molecular assessments were centralised, blinded and calculated according to the international standardised ratio (IS) As of December 31st 2010, date for closing accrual, 787 pts have been included. We first demonstrated that the addition of PegIFN increased the molecular responses. The planned molecular analysis after 1 year based on the outcome of 636 pts resulted in a highly significant superiority of MR4 (≤0.01 % Bcr-Abl/Abl on IS) of the combination IM 400mg-PegIFN (Preudhomme et al. N Engl J Med, 2010). The protocol was also amended after the demonstration that a lower dose of PegIFN (45 µg/week) resulted in less toxicity and similar molecular responses as compared with 90 µg/week. Of interest, a 3-months BCR-ABL transcript level of ≤10% IS was associated with PFS (Accelerated phase, blast crisis, deaths) and time to progression (TTP) improvement overall. However, results which were observed with the addition of PegIFN or an increased dose of IM frontline do not confirm the relevance of the 10% BCR-ABL cut-off level as a strong surrogate marker for progression. After a median observation time of 60 months, 5-year overall survival (OS) was 94%, and 5-year PFS was 93%. Overall 70 pts died because of blastic (n=24) or accelerated phases (n = 1). Out of the 35 pts who progressed to AP and BC, 11 are alive. A blastic phase was recorded in 27 pts (myeloid 20, lymphoid 6, biphenotypic 1), of these 4 are alive (2 myeloid, 2 lymphoid). Main causes of deaths in CP (n = 46) were infections (IM 400 n=4,IM 600 n=0, IM PegIFN n=4, IM Ara-c n=0 ), vascular events (IM 400 n=1,IM 600 n=2,IM PegIFN n=1, IM Ara-c n=1) malignancies (IM 400 n=3, IM 600 n=2 ,IM PegIFN n=4, IM Ara-c n=7 ). In addition, the following causes of death were recorded: suicide (n=2), GVHD (n=2), miscellaneous (n=13). Cumulative incidence of progression, PFS and OS by arms are shown in the table: Table 1 IM 400 (n = 223) IM 600 (n = 171) IM PegIFN (n = 221) IM Ara-c (n 172) Cumulative incidence of progression (p: 0.43)(a) N progressions 11 11 7 6 N competing events (deaths in CP) 9 7 15 15 At 60 months % (95%CI) 5% (3-8) 5% (3-9) 2% (1-4) 4% (2-8) PFS (p:0.92)(b) N (progressions and deaths) 20 18 22 21 At 60 months 93% 93% 94% 91% (95%CI) (89-96) (88-96) (90-97) (85-94) OS (p: 0.64)(b) N (deaths) 15 16 19 20 At 60 months 95% 94% 95% 91% (95%CI) (91-98) (89-97) (91-97) (86-95) Gray’s test Log-rank test Conclusions:The French SPIRIT trial demonstrated that the combination of imatinib with Peg-IFNα2a was associated with deeper molecular responses at 12 months and was able to counteract the risk of early progression in newly diagnosed CML-CP patients. The dose of 45µg/week is well tolerated and sufficient for achieving molecular responses and should be used in further trials. The risk of progression to blastic or accelerated phase, although currently non-significant, is lower with this combination. An update of outcomes will be presented. Disclosures Maloisel: Hospira: Consultancy; Sandoz: Research Funding; Pfizer: Research Funding. Gardembas:BMS: Honoraria. Legros:Novartis, BMS: Honoraria.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2014
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 8
    In: Blood, American Society of Hematology, Vol. 114, No. 22 ( 2009-11-20), p. 340-340
    Abstract: Abstract 340 Background: IM 400 mg daily is the front-line treatment of CP CML, but provides only 50% major molecular responses (MMR) at 18 months (Mo). Aims: we designed a phase III randomized multicenter open-label prospective trial comparing IM 400 mg/d (n=159) with 3 experimental arms: IM 600 mg/d (n=160), IM 400 mg/d combined to s/c cytarabine (Ara-C), (20 mg/m2/d, d15-28 of 28-day cycles)(n=158) and IM 400 mg/d combined to s/c Peg-IFN2a (90 μg/wk) (n=159). Methods: Pts were allocated at a 1.1.1.1 ratio, stratified by Sokal risk groups. Molecular assessments were centralized, blinded and calculated according to the international standardized scale (IS). The purpose of this trial was to first determine whether higher doses of IM or combining IM with interferon or Ara-C would result in higher rates of molecular responses and if so, in better survival. Thus the trial was designed to be conducted according to 2 parts. During the part 1, the increased dose of IM or a combination regimen would be considered as promising at 1 year, if it increased the 4 log reduction response rate by at least 20 percentage points, e.g. from 15% to 35%, with an acceptable tolerability A planned interim analysis of 636 pts based on an optimal molecular response (OMR = BCR-ABL/ABL ratio ≤ 0.01) (α=0.85%, β=10%) at 1 year has suggested the superiority of the combination of Peg-IFN2a and imatinib (ASH 2008). We now report the 18 months update of this planned interim analysis of part 1 of the trial. Results: Pts of the part 1 were recruited between 9/2003 and 10/2007, median age 51 yrs (18-82), 62% males; Sokal score was low 37%, intermediate 39% and high risk 24%. Median follow-up was 42 Mo. (range 18-73) for alive patients. MMR, OMR and undectable molecular residual disease (UMRD) rates are described in Table 1. During the first year of treatment the median dose of IM was 400 mg for the 3 arms including IM 400 and 590 mg for IM 600; the median dose for Peg IFN2a was 54 μg per week (range11-166) and was 24mg per day (range 10-40) for Ara-C. Overall, 45% of the pts discontinued Peg-IFN2a during the first 12 months. Of interest, duration of treatment with Peg-IFN2a had an impact on responses. In pts who have been treated less than 4 months as compare to more than 12 months, rate of MMR, OMR and UMRD increased from 48% to 82%, 23% to 49% and 8% to 20% respectively. Grade 3/4 neutropenia and/or thrombocytopenia occurred during the first year in 8% IM-400, in 14% IM-600, in 41% IM-Ara-C and in 40% IM-PegIFN arms respectively. No significant infection rates were observed between the 4 arms. Grade 3/4 non-haematological toxicities occurred in 19% IM-400 (oedemas, muscle cramps), in 30% IM-600, in 27% IM-Ara-C (diarrhoea) and in 31% IM-PegIFN pts (skin rashes, asthenia). Conclusions: Based on these results and as recommended by the Independent Data and Ethics Monitoring Board, the CML French Group (FI-LMC) stopped accrual into the IM 600mg and IM 400mg + Ara-C arms and is currently continuing with IM 400 mg as control arm and the combination IM400mg + Peg-IFN2a as best experimental arm. This second part of the trial aims to confirm if achieving significant higher molecular responses will translate into a better event free and overall survival. Disclosures: Mahon: Amgen: Honoraria; Novartis Pharma: Consultancy, Honoraria, Research Funding; Alexion: Consultancy, Honoraria.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2009
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 9
    In: Blood, American Society of Hematology, Vol. 120, No. 21 ( 2012-11-16), p. 2465-2465
    Abstract: Abstract 2465 Background This study was designed to identify single nucleotide polymorphisms (SNPs) associated with probability of achieving a major molecular response (MMR) in chronic phase CML patients (pts) treated with imatinib. We used a non-commercial, pharmacogenetics-dedicated DNA chip containing 16561 SNPs covering 1916 candidate genes. We tested an exploratory cohort of pts treated with imatinib first line or after interferon therapy and then extended our finding in a validation set of pts included in the French SPIRIT trial (C Preudhomme, NEJM 2011) and randomized to the 400 mg or the 600 mg imatinib arm. Patients and methods Constitutive DNA samples from 312 pts were analyzed: samples from 91 pts in the exploratory set and 221 pts in the validation set (SPIRIT trial: 120 pts within the 400 mg imatinib arm and 101 pts within the 600 mg imatinib arm). We analyzed the expression of BCR-ABL/ABL standardized ratio as a function of the time elapsed since imatinib initiation for each patient using nonlinear (spline) interpolation and then derived the delay to achieve MMR or time of follow-up. With this method, we obtained a cumulative incidence curve of MMR in both groups. Relevant SNPs were identified using a COX model adjusted for covariates (sex, two first principal components and Sokal score when available). SNP with FDR (False Discovery Rate) below 30% in the exploratory cohort where subsequently investigate in the SPIRIT trial groups. Results Patient characteristics such as age, sex, Sokal score were homogeneous between exploratory and validations sets as well as within both arms of the SPIRIT trial. We confirmed the prognostic value of the Sokal score in term of cumulative incidence of MMR (CI-MMR) in both sets of pts (CI-MMR was 83%, 67% and 56% for low, intermediate and hight Sokal risk groups respectively, additive log rank, p 〈 0.001), as well as the significant improvement of CI-MMR within the SPIRIT trial for pts assigned to the 600 mg daily imatinib arm as compared to the 400 mg daily arm (CI-MMR was 80% in the 600 mg imatinib arm compared to 61% in 400 mg/day arm, log rank, p = 0.008). CI-MMR was similar between exploratory set and the 400 mg/day arm of the SPIRIT trial (63% vs 61%, log rank, p = 0.56) and higher in the 600 mg arm of the SPIRIT trial compared to the exploratory set: 80% vs 63% (log rank, p 〈 0.001), consistent with dose received in the exploratory set (imatinib 400 mg/d). Association study shows that 10 SNPs identified pts with significantly different probability to achieve MMR within the two first year of therapy (FDR less than 30% p 〈 0,01) in the exploratory cohort three of which belong to ABCG2 gene. In the SPIRIT trial (n=221), only two SNPs from ABCG2 locus were significantly associated with a higher probability of achieving MMR. We then analyzed separately both arms of the SPIRIT trial. All tree ABCG2-SNPs identified in the exploratory set of pts were significantly associated with CI-MMR in the 400 arm at the 5% level. In contrast, none of them were confirmed in the 600 mg arm. In order generalize our results and to get closer to the underling molecular structure of genotypes markers we performed haplotyping at locus of ABCG2 gene. Multivariate analysis distinguished two minor haplotypes (haplotype 1 and 3) linked to MMR achievement in pts receiving 400 mg/day of imatinib (from exploratory set and SPIRIT, n=211). Haplotypes 1 had G-C-G and haplotype 2 had G-T-G at rs12505410, rs13120400 and rs2725252 respectively and their frequencies were 26 and 6% respectively. Collapsing these haplotypes yielded a surrogate dominant marker highly associated to CI-MMR in this group (p 〈 0.001, figure 1A) whereas in the SPIRIT 600 mg arm, this phenomenon did not hold anymore (p=0.25, figure 1B). Interestingly, CI-MMR in the 400 mg/day harboring a copy of minor haplotypes (1 or 3) was comparable to the CI-MMR observed in pts receiving 600 mg/d imatinib lacking of at least one copy of the two minor haplotypes (75% vs 70% respectively, p=0.99) or whatever haplotype they had (75% vs 80%, p=0.37). Conclusion The ABCG2 gene product is a well-known protein involved in drug absorption in the bowel. Polymorphism of the ABCG2 gene has been implicated in drugs absorption including imatinib. We here confirm that ABCG2 haplotypes could distinguish patients at a lower probability to achieve MMR. We report for the first time that this unfavorable pharmacologic effect can be overcome in vivo by increasing imatinib daily dose from 400 mg to 600 mg. Disclosures: Rousselot: BMS, Novartis: Research Funding. Guilhot:ARIAD: Honoraria.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2012
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 10
    In: Blood, American Society of Hematology, Vol. 122, No. 21 ( 2013-11-15), p. 654-654
    Abstract: In the Stop imatinib study (STIM)1, we previously demonstrated that Imatinib could be safely discontinued in patients with a sustained deep molecular response (DMR) (undetectable BCR-ABLtranscripts (UMRD) for at least 2 years) (Lancet oncology, 2010;11: 1029-1035). Recently, these results were confirmed by the Australasian TWISTER study using criteria of imatinib cessation very similar to those used in the STIM1 study (Blood, 2013; 122:515-22). However in the both studies, half of the patients were previously treated with IFN leading to a non-homogenous cohort of patients. So we conducted prospectively a second trial (STIM2) where cessation of imatinib treatment was proposed for patients in sustained DMR who were treated only with imatinib. Methods In this new multicenter, non-randomized STIM2 study (ClinicalTrials.gov, NCT01343173), imatinib was discontinued in CML pts with the same criteria as those we reported previously for the STIM1 i.e. sustained DMR defined as remission lasting more than 2 consecutive years and confirmed on five datapoints of BCR–ABL analyses by quantitative RT-PCR during these 2 years. The UMRD was defined with a sensitivity 〉 to 4.5 log with ≥ 50.000 ABL transcripts amplified as internal control. The molecular relapse was defined as positivity of BCR–ABL transcript in Quantitative RT-PCR confirmed by a second analysis point indicating the increase of one log in relation to the first analysis point, on two successive assessments, or loss of MMR at one point. Quantitative RT-PCR for BCR–ABL transcripts from peripheral blood was performed every month during the first year and every 2 months thereafter. Beyond 2 years, molecular biology FU was performed every 3 months. Results From April 2011 to June 2013, 124 CML pts were included (62 men,62 women) with a median age of 61 years recruited in the 23 French centers. At the last update, the median follow up of the first 124 pts enrolled is 12 months (range 1-25). After discontinuation of imatinib, a molecular relapse occurred in 48 pts (45 relapses during the first 6 months and 3 relapses between 6 and 12 month), and 76 patients were still free of treatment at the last update with DMR. However 41 experienced a BCR-ABL RQ-PCR fluctuation without clear molecular relapse. In this so-called-fluctuation group of patients, 7 were found positive once, 6 twice, 12 patients between 3 and 5 times, 10 patients between 6 and 10 times and 6 patients more than 10 times confirming that BCR-ABL reappearance does not mean automatically clinical relapse. We confirmed also that all patients were sensitive to a TKI re-challenge. Actually, 33 patients were retreated with imatinib 5 with nilotinib and 3 with dasatinib. The median time to achieve again a CMR from the molecular relapse was 7 months (range 4-16 months) and from re-initiation of TKI was 4 months (range 2-14). Taking into account the cost of imatinib and the number of months without treatment in the total study population at last analysis, the savings within the STIM2 trial were estimated at 2.8 millions Euros. Conclusion We confirm that Imatinib can be safely and prospectively discontinued in pts with DMR of at least 2 years duration in patients only treated with imatinib. To stop treatment it may not require the complete eradication of residual leukemic stem cells since positive fluctuation PCR results do not lead to CML relapse or progression. These intriguing results, even for imatinib treated patients since disease onset (already observed after IFN therapy), are comparable to those reported with the more sensitive PCR on DNA in the TWISTER study and are under investigations in our laboratory. Disclosures: Mahon: Novartis: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding; Brisol Myers Squibb: Consultancy, Honoraria; Ariad: Honoraria; Pfizer: Honoraria. Nicolini:Novartis, Ariad, Teva, BMS and Pfizer: Honoraria from Novartis, Ariad, Teva, BMS and Pfizer. Grants from Novartis. Other. Rea:Novartis: Honoraria; Bristol Myers Squibb: Honoraria; Pfizer: Honoraria; Ariad: Honoraria. Etienne:novartis: Consultancy, Membership on an entity’s Board of Directors or advisory committees; Bristol Myers Squibb: Consultancy, Membership on an entity’s Board of Directors or advisory committees; Pfizer: Membership on an entity’s Board of Directors or advisory committees; Ariad: Membership on an entity’s Board of Directors or advisory committees.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2013
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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