Univ Estadual Campinas, Hematol & Hemotherapy Ctr, Campinas, SP, BrazilUniv Fed Minas Gerais, Hosp Clin, Belo Horizonte, MG, BrazilInst Nacl Cancer, Rio De Janeiro, BrazilFac Med, Sao Paulo, BrazilUniv Sao Paulo, Sao Paulo, BrazilHemorio, Rio De Janeiro, BrazilHosp Clin Porto Alegre, Porto Alegre, RS, BrazilCtr Pesquisa Oncol Santa Catarina, Florianopolis, SC, BrazilUniv Fed Bahia, Salvador, BA, BrazilUniv Fed Sao Paulo, Sao Paulo, BrazilInst Estudos & Pesquisas Sao Lucas, Sao Paulo, BrazilUniv Estadual Campinas, Campinas, SP, BrazilUniv Fed Sao Paulo, Sao Paulo, BrazilWeb of Scienc

Bendit, I.

Boquimpani, C.

Bortolini, J.

Centrone, R.

Chauffaille, M. D. L.

Clementino, N.

Coelho, A.

De Souza, C.

Fogliatto, L.

Magalhaes, G.

Miranda, E.

Nicolau da Silva, M.

Pagnano, K.

Pinna, C.

Seguro, F.

Haematologica

English

Chauffaille, M. D. L. [UNIFESP]

Repositório Institucional UNIFESP

Three patients (2 IM/HU, 1IM) were lost to follow-up. As prospectively designed,all available IM/HU patients (n=77) were analyzed together. According to thestudy protocol, patients from the CML IV study were to be added to obtainequal numbers for analysis. To arrive at a total of 77 IM patients, from study IVanother 49 patients were selected by propensity score matching. The medianage of the 154 patients was 55 years (range 18 – 82). The ELTS prognosticscore was available for 141 patients and was high in 8 (5.7%), intermediate in35 (24.8%) and low in 98 (69.5%), with no significant differences between treat-ment groups.Results: The 5-year overall survival (OS) / progression-free survival (PFS)probabilities were 90.4 and 86.7% in the IM/HU and twice 84.9% in the IMarm (p=not significant). With IM/HU, the probabilities of complete cytogeneticresponse (CCR) at 6, 12, and 18 months were 54.3, 84.0, and 93.7%. In theIM arm, the corresponding numbers were 70.4, 84.9, and 83.3% (p=not sig-nificant). Primary endpoint was MMR rate at 18 months. There was no sig-nificant difference between IM/HU (65.8%) and IM (66.0%). At 6 months,MMR rates were 21.6 (IM/HU) vs 41.1% (p=0.0383) and at 12 months 41.9(IM/HU) vs 58.9% (not significant). Time to event analyses of OS and PFSdid not result in significant differences; neither did group comparisonsbetween the probabilities of CCR and MMR. The median HU dose was500mg (range 152-3000); the median IM dose was 400 mg (range 145-617mg) in both arms. The gross numbers of adverse events in general or ofadverse events of grade 4 were not different between the two arms, butcumulative incidences showed an earlier occurrence in the IM/HU than inthe IM arm (p= 0.0343, Gray test)Summary/Conclusions: Compared to Imatinib only, the combination of Ima-tinib and HU resulted in a lower MMR rate at 6 months but a similar MMR rateat 18 months. Furthermore, IM/HU was associated with more early adverseevents. There was no indication of a beneficial effect in the treatment of CMLpatients in 1st chronic phase using the combination of IM with HU.PB1820A MULTICENTER, OBSERVATIONAL, AMBISPECTIVE STUDYEVALUATING EFFICACY AND SAFETY OF GENERIC IMATINIBCOMPARED TO GLEEVEC IN CHRONIC MYELOGENOUS LEUKEMIA INCHRONIC PHASE - 3 MONTHS RESPONSE ANALYSISK. Pagnano1,*, E. Miranda1, N. Clementino2, G. Magalhães2, A. Coelho3,I. Bendit4, F. Seguro5, M. Nicolau da Silva3, C. Boquimpani6, L. Fogliatto7,J. Bortolini8, C. Pinna9, M. D. L. Chauffaille10, R. Centrone11, C. De Souza121Hematology and Hemotherapy Center, University of Campinas, Campinas,2Hospital das Clínicas-Universidade Federal de Minas Gerais, Belo Horizonte,3Instituto Nacional do Câncer, Rio de Janeiro, 4Faculdade de Medicina, 5Uni-versidade de São Paulo, São Paulo, 6Hemorio, Rio de Janeiro, 7Hospital deClínicas de Porto Alegre, Porto Alegre, 8Centro de Pesquisa Oncológicas deSanta Catarina, Florianópolis, 9Universidade Federal da Bahia, Salvador,10Universidade Federal de São Paulo, 11Instituto de Estudos e Pesquisas SãoLucas, São Paulo, 12University of Campinas, Campinas, BrazilBackground: The efficacy of branded imatinib (Gleevec) in the first-line treat-ment of chronic myeloid leukemia (CML) has been demonstrated in severalclinical studies. However, there are few consistent data in the literature on theefficacy and adverse effects of generic formulations of imatinib. In Brazil, CMLpatients have been treated in the national public health system with genericimatinib since June 2013. Aims: The present study aims to evaluate the efficacy and safety of genericimatinib in the treatment of CML in comparison with the reference drug(Gleevec) in the first three months of imatinib treatment.Methods: This is a multicenter, observational, ambispective, cohort-type study.The study was initiated in January 2015 with the intended participation of 17Brazilian centers. In the prospective group, were selected chronic phase CMLpatients who started their first-line treatment with generic imatinib betweenJanuary 2015 and October 2016, whereas retrospective group was treatedwith Gleevecbetween January 2010 and December 2011. All patients startedimatinib less than six months from diagnosis. Study data were collected andmanaged using REDCap electronic data capture tools. Demographic data werecollected at diagnosis: age, gender, Sokal, Hasford, EUTOS score, comorbidi-ties, cytogenetics, BCR-ABL transcript type. The definition of the responsesfollowed the European Leukemia Net 2013 criteria. Adverse events wereassessed based on the Common Terminology Criteria for Adverse Events(CTCAE) Version 4.0.3, 2010. Statistical analysis: SPSS version 21.0 wasused applying the chi-square and t-test, when adequate. All analysis consideredp-value <0.05 as significant.Results: Ten centers have registered 177 patients in the retrospective groupand 68 patients in the prospective group so far. For this preliminary analysis,response data from 132 patients were available (47 from prospective and 85from the retrospective groups). The median age of patients was 54 years inthe prospective group and 46 years in the retrospective group (P=0.12). Sokalscore in prospective and retrospective groups, respectively: low risk42%/52%; intermediate risk 42%/31% and high risk 45%/67% (P=0.48).There was no difference between the groups concerning gender, Hasford,EUTOS scores, ECOG, blood cell counts at diagnosis and before startingimatinib and BCR-ABL transcripts. Regarding responses, there was no dif-ference in the hematological, complete cytogenetic responses and rate ofBCR-ABL transcripts >10% at three months. However, there was a higherrate of failure at three months according to the ELN 2013 criteria in theprospective group (14.9% versus 4.7% Gleevec group, P=0.04). There wasno significant difference in grade 3 and 4 hematological and non-hematolog-ical toxicity, but there was one early death in the prospective group (acuteperipheral arterial occlusion and renal failure). Four patients discontinuedimatinib: one from Gleevec group (resistance) and three from the genericgroup due to intolerance (1) and resistance (2). Summary/Conclusions: According to ELN-2013 criteria, there was a higherrate of failure in the prospective group (generic Imatinib) at three months, butno difference in toxicity. The register is ongoing; the confirmation of this dataand the impact in prognosis will be evaluated in the long-term follow-up, afterincreasing the number of patients. PB1821COMPLEX ADDITIONAL CHROMOSOME ABERRATIONS IN PH-POSITIVECELLS IMPACT ON CHRONIC MYELOID LEUKEMIA PATIENTS’ SURVIVALIN THE ERA OF TYROSINE KINASE INHIBITORSM. Fominykh1,*, O. Shuhov2, I. Martynkevich1, V. Shuvaev1, E. Chelysheva2,A. Turkina21Clinical department, Russian Research Institute of Hematology and Transfu-siology, Saint-Petersburg, 2Clinical department, National Research Center forHematology, Moscow, Russian FederationBackground: Additional chromosomal aberrations (ACA) as marker of clonalevolution in chronic myeloid leukemia (CML) patients were previously noted inassociation with resistance to therapy. The presents of ACA have been asso-ciated with a worse prognosis for survival in the pre-TKI era. The ACA classi-fication proposed earlier was based only on its frequencies. Whereas ACA’sclinical impact had not yet been clearly established.Aims: The aim of our study was to evaluate the long-term impact of the ACApresence in Ph-positive cells in CML patients on TKI treatment results.Methods: 30 patients with ACA in Ph-positive cells treated in our center from2005 to 2015 years were included in this study. Cytogenetic analyses of atleast 20 Giemsa-banded bone marrow metaphases were interpreted perISCN 2013. We analyzed overall survival (OS) and cumulative incidence ofCML-related death on TKI treatment. Cox regression was used for multivari-ate survival analysis, that included next covariates: number of ACA, type ofACA, age, TKI type, CP or AP at diagnosis. OS was estimated by Kaplan-Meier method with log-rank test for comparison. Cumulative incidence ofCML-related death was estimated into consideration the presents of com-peting risks (CML-unrelated death) using Gray’s test for comparison betweengroups. Results: Median follow-up period in ACA group (n=30) was 51 months (3-124). ACA at diagnosis were detected in 16 (53%) of 30 patients. Chronicphase CML at diagnosis was determined in 23 (77%) patients. Imatinib wasused as first-line in 20 (67%) patients, 3 (10%) patients were initially treatedwith Nilotinib. Accelerated phase was defined in 7 (23%) patients. In thatgroup treatment of 6 patients was started with Imatinib and Dasatinib wasgiven initially for one patient. «Major-route» ACAs (trisomy 8,+der(22)t(9;22)(q34;q11), i(17)(q10), trisomy 19,) were detected in 16 (53%)of 30 patients. Complex aberrations (2 ACA and more) were revealed in 7(23%) patients, 4 patients from this group had «major-route» ACA. 10-yearsOS in the whole ACA group was 67%, 10-years cumulative incidence of CML-related death was 23%. Number of ACA (p=0.03, HR=13.2) and age (p=0.03,HR=1.14) had statistical significance influence on survival by regressionanalysis. 10-years OS was 31% and 77% (p<0.05) in patients with complexACA and single ACA respectively, 10-years cumulative incidence of CML-related death was 54% for patients with complex aberrations versus 10% forsingle ACA patients (p<0.05) (Figure 1).Figure 1.Summary/Conclusions: Our results showed that TKI treated CML patientswith complex ACAs have a higher risk of progression and death in comparisonwith single-ACA patients. 730 | haematologica | 2017; 102(s1)22nd Congress of the European Hematology Association

A MULTICENTER, OBSERVATIONAL, AMBISPECTIVE STUDY EVALUATING EFFICACY AND SAFETY OF GENERIC IMATINIB COMPARED TO GLEEVEC IN CHRONIC MYELOGENOUS LEUKEMIA IN CHRONIC PHASE-3 MONTHS RESPONSE ANALYSIS

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A MULTICENTER, OBSERVATIONAL, AMBISPECTIVE STUDY EVALUATING EFFICACY AND SAFETY OF GENERIC IMATINIB COMPARED TO GLEEVEC IN CHRONIC MYELOGENOUS LEUKEMIA IN CHRONIC PHASE-3 MONTHS RESPONSE ANALYSIS

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