ALBERT

Beschreibung: Second-generation tyrosine kinase inhibitors (2G-TKI), nilotinib or dasatinib used after imatinib failure can induce complete cytogenetic response (CCR) in 50% of chronic myeloid leukemia (CML) patients. BCR-ABL transcript levels reduction in the initial months of treatment has been associated improved outcome. Aims to evaluate the predictive value of early molecular responses, at 3 and 6 months after treatment with 2G-TKI in CML patients with imatinib failure or intolerance; to correlate these responses with CCR, overall survival (OS), progression-free survival (PFS) and event free survival (EFS). Methods Between September 2007 and August 2012, 71 consecutive patients with CML resistant or intolerant to imatinib were treated with dasatinib (n= 50) or nilotinib (n=21). BCR-ABL transcripts were measured in peripheral blood using real-time quantitative PCR (RQ-PCR) at 3 months intervals. Results were expressed as BCR-ABL/ABL ratio, with conversion to the international scale (IS). Major molecular response (MMR) was defined as a transcript level ≤ 0.1% (IS). Cytogenetic analysis was performed at baseline, 3, 6, 12 and 18 months after starting therapy with 2G-TKI. BCR-ABL mutation analysis by direct sequencing was investigated in resistant patients. Probabilities of OS, PFS and EFS were calculated using Kaplan-Meier method. An event was defined as the loss of CHR, CCR, progression to advanced phases, death or 2G-TKI discontinuation. The CCR probabilities according to molecular responses were calculated by c2 method and cumulative incidence, considering as competitive event death or progression. Results 71 patients were analyzed, median age of 47 years (15-81); Disease status before 2G-TKI was: 50 (71%) CP; 13 (18%) AP and 8 (11%) BC. Responses: 59/71 (83%) obtained CHR; 38/55 (69%) CCR and 37/60 (62%) MMR. At 3 months of therapy, 81.5% (44/54) had a BCR-ABL ratio ≤10% and at 6 months 66% (33/50) had ≤ 1%. At 3 months, CCR was obtained 65% (19/29) pts with ≤10% RQ-PCR and 16% (1/6) with 〉10% RQ-PCR (p= 0.06). At 6 months, CCR was 100% (12/12) in pts with RQ-PCR ≤ 1% and 14% (1/7) in those with 〉1% (p〈 0.0001). The probability to achieve RQ-PCR 〈 10% at 3 month was 43% (95% CI 32-54%). During treatment 3 (4%) progressed to AP and 5 (7%) to BC. The 5-year probability of OS was 78% (95% CI: 68-88%) albeit by disease status was 86% in CP, 92% in AP and 12% in BC (p〈 0.0001). OS was inferior in pts with RQ-PCR 〉 10% at 3 months (60 vs 84%, p= 0.03) and 〉1% at 6 months (68 vs100%, p= 0.006). PFS was 68% in 5-year, and was lower in BC pts (p〈 0.0001) and pts with RQ-PCR 〉1% at 6 months (p= 0.004). EFS was 53% and lower in BC pts (p〈 0.0001), in pts with RQ-PCR 〉 10% at 3 months (p= 0.005) and 〉 1% at 6 months (p〈 0.0001). RQ-PCR at 3 and 6 months were also predictive of a worse survival when patients in CP were analyzed separately. 2G-TKI was discontinued in 44% (31/71) due to: resistance (n=18), intolerance (n=5), death (n= 3), HSCT (n=3) and loss of follow-up (n=2). Eleven BCR-ABL mutations were detected in 36 pts; 3 previously 2G-TKI (L387M-1, E255K-1, M351T-1) and 9 after therapy (T315I-5, M244V-2, E255V-1, Y253H-1). OS by mutation was 45% with any mutation and 88% with no mutation (p= 0.05). Conclusion BCR-ABL transcript levels at 3 and 6 months can identify patients with worse prognosis and less chance to obtain CCR with 2G-TKI after imatinib treatment. Disclosures: No relevant conflicts of interest to declare.

Beschreibung: Several studies demonstrated the prognostic significance of an early molecular response in chronic myeloid leukemia (CML) patients (pts) treated with imatinib in first line or other tyrosine kinase inhibitors. Aims: The aim of this study was to evaluate the impact of early molecular responses, at 3 and 6 months after treatment with imatinib in CML pts and correlate these responses with CCR, MMR, overall survival (OS) and event free survival (EFS). Patients and Methods Between February 2006 and June 2012, 95  adult pts with newly diagnosed CML in chronic phase (CP) received imatinib 400mg/daily. CP was defined using WHO 2008 criteria. All pts received a short course of hydroxiurea until imatinib was available. Cytogenetic analysis was performed at diagnosis, 3, 6, 12 and 18 months after starting therapy and then every 12-24 months thereafter. BCR-ABL transcripts were measured in peripheral blood at 3-month intervals using quantitative RT-PCR (RQ-PCR). Results were expressed as BCR-ABL/ABL ratio, with conversion to the international scale (IS). Major molecular response (MMR) was defined as a transcript level ≤ 0.1% (IS). Statistical analysis: OS was measured from imatinib start until date of death or last visit. An event was defined as death from any cause. EFS was measured from imatinib start until the first event (loss of complete hematological response (CHR); complete cytogenetic response (CCR), progression to advanced phase, death or imatinib discontinuation) or last visit. OS and EFS rates were calculated using Kaplan-Meier method and log-rank test to compare its curves. The MMR probabilities according to molecular responses at 3 and 6 months were calculated by c2 method and cumulative incidence, considering as competitive event death or progression, before the event. Results 95 pts were analyzed, 57 (60%) male, with a median age of 47 years (17-79); Sokal score: high, intermediate and low was 30, 38.6 and 31.4% respectively; EUTOS scores was 81.5% low and 18.5% high. The median time from diagnosis until imatinib therapy was 1 month (0-5) and the follow-up was 39 month (3-89). Responses: 88% achieved CHR; 50% CCR and 53% MMR. One patient progressed to advanced phase during follow-up, while on imatinib treatment. 21 (22%) pts discontinued imatinib due to intolerance (47.6%); resistance (42.9%), death (4.8%) and Allo-HSCT (4.8%). At 3 months from the start of therapy, 30/64 (46.8%) achieved CCR, 15/64 (23.4%) partial cytogenetic response and 20/64 (31.2%) less than partial; by RQ-PCR, 72.3% (68/94) achieved at 3 months BCR-ABL transcripts ≤10% and 27.7% (26/94) 〉 10%. At 6 months 55.2% (48/87) had BCR-ABL transcripts ≤ 1% and 44.8% (39/87) 〉1%. The OS was 97% (95%CI: 95-99%) and EFS 63% (95%CI: 52-75%).There was no significant difference in OS and EFS in pts with RQ-PCR 〉 10% vs ≤ 10% at 3 months (figure 1), but pts with BCR-ABL transcripts 〉 10 and 〉1-10% at 6 months had an inferior EFS in comparison with pts with  BCR-ABL transcripts ≤ 1%  (41%,50%,89% respectively - p= 0.005), (figure 2). The CI showed that CCR pts at 3 months reached MMR earlier at 24 month (54% vs 18%, p=0.03), as well as CCR pts at 6 months, albeit no significance statistically (52% vs 37%, p= 0.16). For RQ-PCR at 3 months, pts with BCR-ABL transcripts 0-1% had a probability of 88% to achieve MMR, 1-10% had 52% and 〉10% 42%, p〈 0.0001 (figure 3). In conclusion, our results show that early molecular responses are predictive of achieving MMR and BCR-ABL transcripts

Beschreibung: Several trials have demonstrated the feasibility of discontinuation of tyrosine kinase inhibitors (TKI) treatment in chronic myeloid leukemia (CML) patients (pts) with deep molecular response. Aims: to report the results of two Brazilian imatinib (IM) discontinuation trials and to evaluate factors impacting in treatment-free remission (TFR) and treatment-free survival (TFS) after IM discontinuation. Methods:Between September 2016 and January 2019, 60 CML pts were included in two ongoing phase II, single arm, prospective Brazilian discontinuation trials: Pilot Study of Discontinuation in Patients With Chronic Myeloid Leukemia With Deep Molecular Response - Evaluation of Pioglitazone in Treatment-free Remission (TFR) (EDI-PIO UNICAMP)(NCT02852486)and Imatinib Discontinuation in Patients With Chronic Myeloid Leukemia Chronic Phase With Sustained MR4log(USP) (NCT03239886). Inclusion criteria: age 〉18 years, chronic phase, minimum of 3 years of IM therapy, deep molecular response for ≥ 2 years (confirmed by 4 tests in the last 2 years, defined as MR4.0 in USP trial and MR4.5 in EDI-PIO). Patients participating in EDI-PIO trial used pioglitazone 30 mg/day plus IM for 3 months before IM discontinuation (n=30). After discontinuation, pts were monitored by quantitative RQ-PCR monthly in the first year, every 2 months in the second year and every 3 months in the third year. Criteria for IM re-initiation: loss of MMR (in one test), loss of cytogenetic response, loss of hematologic response, disease progression or confirmed loss of MR4.0 (this criteria used only in EDI-PIO trial). TFR was calculated from the date of discontinuation until first event (loss of MMR; IM reintroduction; death any cause or last follow-up); TFS was calculated from the date of IM discontinuation until reintroduction or last follow-up (censoring deaths not related to CML). Adverse events after IM discontinuation were reported according to CTCAE. Results:Data cut-off for analysis was February 2019. In the 1stanalysis 48 pts who discontinued IM in MR4.5 were analyzed. Patient's characteristics from EDIPIO (n=30) and USP (n=18) trials were: 57% vs. 67% male, median age of 55 (29-77) and 56 (33-95) years (29-95) at discontinuation; 16% and 33% had used previously Interferon; median duration of IM treatment of 10 (3-16) vs. 10 (5-15) years; median duration of MMR 95 (30-149) vs. 93 (57-130) months; MR4.0 was 90 (26-135) vs. 89 (30-123) months; and MR4.5 was 76 (23-135) vs. 75 (30-102) months; none variable had statistical difference.One patient died in MMR due to cardiac failure. TFR was 61% (95% CI 47-75) at 20 months. Sixteen (33%) out 48 re-initiated IM (2 with confirmed loss of MR4.0 and 14 with loss of MMR) in a median time of 20 (1-26) months. All relapsed pts recovered MMR after IM reintroduction, in a median time of 2 months (0-4). There was no transformation to advanced phases. No serious adverse events were reported during pioglitazone treatment. In the Cox regression the duration of MMR was associated with a longer TFR HR: 0.96 (beta-) (CI 95%:0.94-0.99, P= 0.006). Gender, age at diagnosis, age at discontinuation, treatment with pioglitazone, Sokal and EUTOS scores, BCR-ABL transcripts type, duration of IM therapy, duration of MR4.0 and MR4.5 and previous use of Interferon did not affect TFR.In the second analysis all 60 pts were included. TFS was 56% and was higher in pts who discontinued IM in sustained MR4.5 vs. MR4.0 (63% vs. 33%, P=0.04)(Figure). The independent factors for TFR in the multivariate analysis by Cox-regression were the duration of MMR [HR: 0.97 (beta-), 95%CI: 0.95-0.98, P=0.001] and intermediate/high risk Sokal [HR 3.14 95%CI: 1.08-9.11, P= 0.035]. Twenty-four out of 60 pts (40%) re-initiated IM (2 with confirmed loss of MR4.0 and 22 with loss of MMR).Adverse events occurred in 38 (63%) pts, 30% attributed to withdrawal syndrome. Some pts presented more than one event. Grade 1-2: arthralgia or muscular pain (17), hyperglycemia (4), hypertriglyceridemia (2), polycythemia (2), hypertension (3), and others (11). Four pts had grade 3-4 event: arthralgia (1), death for cardiac failure (1), abortion and hypertriglyceridemia (1). Conclusions:both trials demonstrated the feasibility and safety of IM discontinuation in pts in sustained deep molecular response. The duration of MMR was associated with a higher TFR and TFS rate. Imatinib discontinuation was more successful in pts in stable MR4.5. Figure Disclosures Pagnano: Pint Pharma: Consultancy; Abbvie: Consultancy; Sandoz: Consultancy. Delamain:Novartis: Honoraria.

Beschreibung: Preliminary reports demonstrated that pioglitazone, an antidiabetic drug that is agonist of peroxisome proliferator-activated receptor gamma (PPAR-γ) was able to reduce expression of STAT5 and its downstream targets HIF2α and CITED2, which are key guardians of the quiescence and stemness of chronic myeloid leukemia (CML) leukemia stem cells (LSCs). Leaving quiescence would turn the LSCs more sensitive to imatinib (IM) and cause an erosion of the LSCs. This was demonstrated in vitro and in vivo in CML patients that achieved complete molecular response after pioglitazone use. This was the rational for the design of EDI-PIO trial (Pilot Study of Imatinib Discontinuation in Patients with Chronic Myeloid Leukemia with Deep Molecular Response - Evaluation of Pioglitazone in Treatment-Free Remission) (NCT02852486). In this trial, pioglitazone was given in association with IM, with the aim to pull out the LSCs from the quiescence and sensitizing them to IM effect, increasing treatment-free remission (TFR) rates after treatment interruption. Aims: to evaluate PPAR-γ, STAT5, HIF2α and CITED2 gene expression before and after pioglitazone use in CML patients with criteria for IM discontinuation Patients and methods: EDI-PIO is a prospective, phase II trial. Inclusion criteria: CML in chronic phase, treated with IM for at least 3 years, with stable deep molecular response (MR4.5) for at least 2 years. Patients received pioglitazone 30 mg/day, orally, for 3 months before IM discontinuation. BCR-ABL levels were measured by real-time quantitative PCR monthly in the first year after discontinuation, every two months in the second year, and then every 3 months during the subsequent follow-up. Imatinib was reinitiated at molecular relapse (loss of major molecular response or confirmed loss of MR4.0). Total RNA was extracted from peripheral blood leukocytes, pre and post pioglitazone, and at 3 and 6 months after IM discontinuation. After cDNA synthesis, an aliquot was used for gene expression analysis by reverse transcriptase quantitative polymerase chain reaction (RT-qPCR), using specific primers for PPAR-γ, STAT5, HIF2α and CITED2. The relative gene expression was calculated using the equation, 2-ΔΔCT. GAPDH was used as control gene. Statistical analysis was performed using ANOVA. Treatment-free remission (TFR) was calculated from IM discontinuation until molecular relapse, reintroduction of IM by any cause, progression to advanced phases or death to any cause. Results: The study is closed for enrollment. Between June 2016 and January 2019, 32 chronic phase CML patients were recruited, of which 30 patients were included in gene expression analysis. Median age was 55 years at trial initiation; 56.7% were men, 50% low risk Sokal and the median time of IM treatment was 117 months (41-191). The median follow-up time was 20 months. TFR was 60% at 24 months. Eleven patients relapsed and IM was reintroduced, but none presented hematologic relapse or progression to advanced phases. There was no significant difference in STAT5, PPAR-γ, HIF2α and CITED2 expression pre and post pioglitazone, at 3 and 6 months after IM discontinuation. No difference was found in the comparison of the relapsed vs. non-relapsed group. Conclusions: pioglitazone did not affect STAT5, PPAR-γ, HIF2α and CITED2 gene expression in this group of pts with deep molecular response. The ACTIM trial demonstrated a reduction in STAT5 expression in bone marrow cells 6 months after pioglitazone exposure, but pioglitazone was given to pts with MMR, without MR4.0. There was no difference in gene expression in the groups with or without molecular relapse. TFR rates remains similar to those reported in other discontinuation trials. Disclosures Delamain: Novartis: Honoraria. Pagnano:Sandoz: Consultancy; Pint Pharma: Consultancy; Abbvie: Consultancy.

Beschreibung: Introduction: The achievement of a deep and sustained molecular response after treatment with tyrosine kinase inhibitors (TKI) is one of the requirements for therapy discontinuation in chronic myeloid leukemia (CML) patients. Objectives: This study aimed to evaluate the proportion of CML patients treated with imatinib in first-line that achieve MR4.5 (BCR-ABL transcripts ≤ 0.0032% in the international scale) after imatinib treatment and the predictive factors for this response. The secondary objectives were to evaluate the rate of MMR (PCR ≤0.1%), MR4.0 (PCR ≤ 0.01%), time to molecular responses, event-free survival, progression-free and overall survival. Patients and methods: This is a retrospective analysis of CP-CML patients treated in first-line with imatinib in a single center. Patients diagnosed after 2006 were managed according to the European Leukemia Net recommendations. All patients started CML imatinib within six months from diagnosis. The type of BCR-ABL1 transcript was determined by multiplex RT-PCR from cDNA synthesized from total leukocytes RNA at diagnosis. BCR-ABL transcripts by quantitative real-time polymerase chain reaction were assessed at baseline, and then every three months for the first year until reaching a stable major molecular response, then every 3-6 months. The SPSS software was used for the Cox Regression model for univariate and multivariate analysis, using backward Wald. The cumulative incidence was calculated with the R Program, with Gray test for curve comparisons. Event-free, progression-free and overall survivals were calculated with the Kaplan-Meier method, and the curves were compared with the log-rank test. Results: From January 2005 to December 2015 172 patients were treated with imatinib, median age 48 years (18-93), 55.8% male. Sokal score: 31% low-risk, 40% intermediate-risk and 29% high-risk. The median follow-up was 56 months (0-157). The Cumulative Incidence (CI) of MMR was 48% in 24 months and 84% in 5 years, while the CI of MR4.0 and MR4.5 was 63% and 51%, respectively, in 5 years. The median time to MMR, MR4.0 and MR4.5 was 16.7 (2-102), 31 (5-150) and 36 months (7-153), respectively. The univariate regression factors related to MR4.5 achievement were: age 〉48 years (HR 1.79; 95%CI: 1.08-2.98; P=0.023); days between diagnosis and imatinib start (HR=0.99; 95%CI: 0.98-0.99, P=0.020); e14a2 (b3a2) transcript (HR= 3.37; 95%CI: 1.67-6.81; P=0.001), which was the only factor in the multivariate analysis. Imatinib was discontinued in 96/172 (55.8%) patients due to resistance (36.5%), intolerance (20.8%), clinical trials (25%), death (15.6%) and adherence (2.1%). Eighteen out of 67 (26.8%) patients that achieved MR4.5 are currently participating in a discontinuation trial. Overall survival, PFS and EFS were 92%, 87% and 61% in 5 years. Conclusion: Approximately half of the patients that start imatinib in first-line obtain deep molecular responses within five years and could be candidates for treatment discontinuation. B3a2 transcript was an independent factor for MR4.5 achievement in the multivariate analysis, confirming the results of other studies that have reported earlier and deeper molecular responses in patients with b3a2 transcripts. Disclosures De Paula: Hematology and Transfusion Medicine Center, University of Campinas: Employment. Pagnano:Abbvie: Consultancy; EMS: Other: Financial support for participation in congress; Shire: Other: Lecture; Novartis: Consultancy.

Beschreibung: The prognostic significance of BCR-ABL1 transcripts in chronic myeloid leukemia (CML) is controversial. A recent report demonstrated that patients with e13a2 transcripts have inferior outcomes with imatinib 400 mg and those patients with e14a2 or that express both transcripts have more chance of an optimal response and longer event-free and transformation-free survival, while others do not confirm this data.The aim of this study was to evaluate the impact of BCR-ABL transcript type in CML patients outcome.Patients and methods: all consecutive CML patients in chronic phase treated with imatinib 400 mg/day from February 2004 to January 2016 were enrolled. Patients' responses were monitored with cytogenetic analysis at 3, 6 and 12 months, then every six months until a complete cytogenetic response (CCR). Real-time polymerase chain reaction was assessed at baseline, then every 3 months for the first year until reaching a stable major molecular response, then every 3-6 months. Demographic and baseline disease characteristics were collected at diagnosis. The type of BCR-ABL1 transcript was evaluated by multiplex RT-PCR from cDNA synthesized from total leukocytes RNA at diagnosis. We included patients with BCR-ABL transcripts e13a2, e14a2, and with coexpression of e13a2 and e14a2. Statistical analysis: Event-free survival (EFS) was measured from the start of treatment until loss of complete hematologic response, loss of major cytogenetic response, progression to accelerated (AP) or blast phase (BC) or death from any cause at any time while on initial therapy. Overall survival (OS) was measured from the start of imatinib until to the date of death from any cause at any time or last follow-up. Transformation-free survival (TFS) was measured from the start of imatinib to transformation to AP or BC or deaths while on therapy. The differences between variables were analyzed by the χ2 and the Kruskal-Wallis tests for categorical and continuous variables. Survival probabilities were calculated using the Kaplan-Meier method and compared by the log-rank test. The Cox regression estimated the hazard ratio values. All analysis considering p-value 〈 0.05 and using SPSS 21.0 software. Results: A total of 190 patients were treated with imatinib 400 mg/day. Median age was 48 years (18-87) and Sokal risk was high in 47/151 patients (31%), intermediate in 55/151 (36%) and low in 49/151 (33%). Twenty patients were excluded from the analysis: 14 patients due to Interferon treatment before Imatinib; two patients that started imatinib after six months from diagnosis; two patients with e1a2 transcripts and two patients with no RT-PCR test available at diagnosis. The remaining 170 patients presented typical BCR-ABL1 transcripts: e13a2 (n=56; 33%), e14a2 (n=94; 55%) and both transcripts (n=20; 12%). A total of 44 (26%) patients discontinued imatinib and 24 (14%) switched to second-line tyrosine kinase inhibitor. No differences were observed in sex, age, leukocytes, hemoglobin and platelets count at diagnosis, Sokal or EUTOS score according to transcript type. The proportion of patients with e13a2, e14a2 and both achieving complete cytogenetic response at 6 months was 19/44 (43%); 42/60 (70%) and 9/14 (64%) (P=0.02); and at 12 months was 28/45 (62%); 47/60 (78%) and 11/14 (78%) (P=0.16). However, the proportion of patients with major or lower molecular responses at 18 months was 13/24 (54%), 25/36 (69%) and 6/9 (66%), which was not significantly different. There were no statistical difference in EFS, PFS, and OS among the e13a2, e14a2 and e14a2+e13a2 groups. However, there was a superior 10-year overall survival in patients with transcripts e13a2 compared to e14a2 (alone or coexpressed with e13a2) (93% vs. 73%, P=0.03), although the 5-year overall survival was 96% vs. 88%, respectively (P=NS). In the multivariate analysis, high/intermediate Sokal score and e14a3/e14a3+e14a2 were independent factors for poor OS (P=0.023 and 0.041, respectively).Conclusion: The type of BCR-ABL transcripts did not affect molecular responses. Although patients with e14a2 transcripts presented higher rates of CCR at 6 months, compared to e13a2 or both transcripts, at long term, there was a superior overall survival among patients with transcripts e13a2 compared to e14a2 (alone or coexpressed with e13a2). The biological mechanism responsible for that difference is not known and should be investigated in larger trials. Disclosures Pagnano: Novartis: Consultancy, Honoraria; Bristol-Meyers Squibb: Consultancy, Honoraria.

Beschreibung: Abstract 3787 Dasatinib is effective at inducing complete cytogenetic response (CCyR) in approximately half of chronic myeloid leukemia (CML) patients treated in the chronic phase (CP) after failing imatinib. The aim of this work was to evaluate the role of molecular monitoring in predicting the outcome of patients treated with dasatinib after imatinib therapy. Between 2008 and 2012, it was analyzed 55 consecutive patients with CML with imatinib intolerance or resistance treated in a single center. Patients received dasatinib (50–140 mg) as second or third line therapy. Cytogenetic analysis was performed at 3, 6, 12 and 18 months after dasatinib introduction. BCR-ABL1 transcripts were measured in the blood at 3 months intervals using real-time quantitative PCR (RQ-PCR). Results were expressed as percent ratios relative to an ABL1 internal control. Major molecular response (MMR) was defined as a transcript level ≤ 0.1% on the international scale. Kinase domain (KD) mutations were performed before starting therapy and/or after dasatinib resistance. The probabilities of overall survival (OS), progression-free survival (PFS), and event-free survival (EFS) were calculated using the Kaplan-Meier method. An event was defined as the loss of a CCyR or complete hematologic response, progression to AP and BP, death, or discontinuation of dasatinib. The probabilities of cytogenetic and molecular responses were calculated using cumulative incidence (CI) and x2method. Results: 33 patients were male (60%) and 22 female (40%), with median age of 48 years (15–81). At diagnosis Sokal scores were low for 11/34 (32.4%), intermediate for 6 (17.6%) and high for 17 (50%) (21 NA). Thirteen patients had a previous CCyR with imatinib. The median time between diagnosis and dasatinib treatment was 25 (2–223) months. The median follow-up was 12 months. Disease phase at beginning of dasatinib treatment: 32 (58%) CP, 13 (24%) accelerated phase (AP) e 10 (18%) blast phase (BP). Eight-seven percent achieved RHC, 55% CCyR and 38% MMR. At 3 months 67% (25/37) had BCR-ABL1/ABL1 transcript ratio '10%, at 6 months 48% (14/29) ≤ 1% and at 12 months 27% (6/22) RQ-PCR ≤ 0.1%. After introduction of dasatinib, patients with the 3-month BCR-ABL1/ABL1 transcript ratio of 〉10% had a lower chance of achieving CCyR (12.5% vs 81.5%, p= 0.001) and MMR (8.3% vs. 58.3%, p= 0.005). Patients with the 6-month BCR-ABL1/ABL1 transcript ratio of 〉1% had a lower chance of achieving CCyR (8% vs. 75%, p= 0.01) and MMR (26.6% vs. 64.2%, p=0.06) compared with patients with ratio ≤ 1%. The probability of OS, PFS and EFS in 48 months while on treatment was 83%, 70% and 29%, respectively. PFS was 88%, 76% e 11% in CP, AP and BP respectively (p〈 0.0001). EFS was 36%, 32% e 10% in CP, AP and BP (P〈 0.0001). Dasatinib was discontinued in 26/55 because of resistance (12), intolerance (5) or transplant (1). BCR-ABL KD mutations were detected in 13/38 cases, two before (L387M e M351T) and 11 during dasatinib treatment (T315I-6, M244V-2, E255V-1, E499E-1, M351T-1). Patients with mutations had an inferior EFS (p=0,05). In conclusion, this study indicates that evaluation of molecular response at 3 and 6 months can identify patients with less chance of response to dasatinib in patients with imatinib failure. The early identification of patients with poor outcome is important for planning future treatments. Disclosures: No relevant conflicts of interest to declare.