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Objetivos Avaliar a efetividade e eficiencia de um protocolo de descontinuacao de inibidores de tirosina quinase (ITK) em tratamento no Sistema Unico de Saude (SUS) que incluiu uma fase de descalonamento de dose antes da interrupcao do tratamento. Materiais e metodos Estudo prospectivo, em andamento. Criterios de inclusao: LMC em fase cronica, em tratamento com ITK no minimo ha 3 anos, transcritos BCR-ABL tipicos, com resposta molecular profunda (RMP) por 2 anos (MR4.5) Exclusao: fase avancada previa ou atual, resistencia previa, mutacoes do ABL. Antes da suspensao do tratamento, foi realizado o descalonamento do ITK para 50% da dose atual por 6 meses. Durante a fase de descalonamento foi realizado monitoramento de PCR quantitativo para BCR-ABL (PCRq) mensal. Apos a descontinuacao do ITK o paciente foi seguido com avaliacoes clinicas, hemograma e PCRq a cada 4 semanas no primeiro semestre, a cada 2 meses no segundo semestre e no segundo ano e depois a cada 3 meses. A terapia foi reiniciada na perda de RMM (PCRq Resultados Entre setembro de 2020 e julho de 2021 foram triados 213 pacientes com LMC; 28 eram potencialmente elegiveis: 9 nao aceitaram participar; 19 assinaram o TCLE e um paciente teve falha de screening. A mediana de idade dos 18 participantes foi de 61.5 anos (35-86), 61% homens, 44.4% Sokal baixo risco ao diagnostico, 15.1% intermediario/alto; 81% com transcrito BCR-ABL do tipo b3a2; 78% estavam em uso de Imatinibe,11% Dasatinibe,5.5% Nilotinibe e 5.5% Bosutinibe. A mediana da duracao do tratamento com ITK ate o inicio do descalonamento foi de 136 meses (46-201); a duracao da RM 4.5 foi de 104, 5 meses (27-168); a mediana do tempo entre suspensao e perda de RMM foi de 2.5 meses (2-3). Oito pacientes perderam a RM4.5 durante a fase de descalonamento: destes, 2 perderam RMM, um na fase de descalonamento e outro na fase de descontinuacao. Status atual: sete pacientes estao na fase de descontinuacao, 8 na fase de descalonamento e 3 pacientes (16.6%) apresentaram recaida molecular. Nao houve nenhum evento adverso serio. Dois pacientes tiveram Covid-19 (leve) na fase de descalonamento. Discussao a descontinuacao tem sido proposta como estrategia terapeutica na pratica clinica nos pacientes com LMC com RM profunda sustentada. Nesses casos, a chance de sobrevida livre de remissao e de 50%. Poucos estudos avaliaram o efeito da retirada gradual do ITK antes da interrupcao. No estudo DESTINY, o descalonamento foi feito por 12 meses, e a sobrevida livre de terapia aos 36 meses foi de 72% nos pacientes com RM4.0. Nos resultados preliminares do nosso estudo, ainda em recrutamento de pacientes, com 10 meses de seguimento, observamos que das 3 recaidas, uma delas ocorreu na fase de descalonamento, em um paciente em uso de nilotinibe em segunda linha e outra em um paciente na segunda tentativa de descontinuacao, onde e esperado uma menor chance de sucesso. Conclusoes ate o momento o protocolo mostrou-se seguro, com resultados dentro do esperado na literatura. O seguimento a longo prazo e inclusao de novos pacientes nos permitira avaliar se a estrategia do descalonamento trara vantagem na sobrevida livre de terapia.

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.

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.

OBJECTIVE: To evaluate hematological, cytogenetic and molecular responses as well as the overall, progression-free and event-free survivals of chronic myeloid leukemia patients treated with a third tyrosine kinase inhibitor after failing to respond to imatinib and nilotinib/dasatinib. METHODS: Bone marrow karyotyping and real-time quantitative polymerase chain reaction were performed at baseline and at 3, 6, 12 and 18 months after the initiation of treatment with a third tyrosine kinase inhibitor. Hematologic, cytogenetic and molecular responses were defined according to the European LeukemiaNet recommendations. BCR-ABL1 mutations were analyzed by Sanger sequencing. RESULTS: We evaluated 25 chronic myeloid leukemia patients who had been previously treated with imatinib and a second tyrosine kinase inhibitor. Nine patients were switched to dasatinib, and 16 patients were switched to nilotinib as a third-line therapy. Of the chronic phase patients (n=18), 89% achieved a complete hematologic response, 13% achieved a complete cytogenetic response and 24% achieved a major molecular response. The following BCR-ABL1 mutations were detected in 6/14 (43%) chronic phase patients: E255V, Y253H, M244V, F317L (2) and F359V. M351T mutation was found in one patient in the accelerated phase of the disease. The five-year overall, progression-free and event-free survivals were 86, 54 and 22% (p

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.

Early reduction of BCR-ABL1 transcript levels has been associated with improved outcome in chronic myeloid leukemia (CML) treatment. We evaluated 54 chronic-phase CML patients treated with imatinib who switched therapy to dasatinib (n = 33) or nilotinib (n = 21). BCR-ABL1 transcript levels were measured in peripheral blood using real-time quantitative PCR (RQ-PCR) every 3 months from the start of second-line treatment. Patients with BCR-ABL transcript levels >10% at 3 months and >1% at 6 months had significantly inferior progression-free (PFS) and event-free survival (EFS) than patients with RQ-PCR 1% at 6 months also had inferior PFS and EFS than patients with RQ-PCR

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.

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 Disclosures: No relevant conflicts of interest to declare.

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.