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The AETHERA trial demonstrated that brentuximab vedotin (BV) consolidation after autologous stem cell transplantation (ASCT) in patients with Hodgkin lymphoma (HL) at high risk of relapse/progression increases progression-free survival (PFS). Patients previously exposed to BV were excluded from that trial. However, BV alone or in combination with chemotherapy is frequently used as front-line treatment and/or pre-ASCT salvage therapy. We analyzed data from 156 patients with high-risk HL who underwent ASCT with (BV-CON, n = 62) or without (non-BV, n = 94) BV consolidation. Fifty-seven patients received BV-based salvage regimens before ASCT. The 3-year overall survival and PFS for all patients were 91.6% and 70.0%, respectively. Multivariate analysis showed that BV-CON was associated with better PFS (HR 0.39, p = 0.01), whereas positive PET at transplant leaded to worse PFS (HR 2.71, p = 0.001). BV-CON improved PFS in PET-positive patients (72.2% vs. 43.0%, p = 0.05), with a beneficial trend observed in PET negative (88.8% vs. 75.2%, p = 0.09). BV-CON patients with or without BV exposure pre-ASCT had a significantly better PFS than non-BV with or without BV pretransplant treatment (HR 0.36, p = 0.004). The efficacy of real-life BV consolidation therapy was similar to that in the AETHERA trial. This therapeutic strategy improves survival independently of BV exposure prior to ASCT.

HemaSphere : open access journal of the European Hematology Association 5(12), e657 (2021). doi:10.1097/HS9.0000000000000657, Published by Wolters Kluwer Health, [Philadelphia, Pennsylvania]

Over half of chronic myeloid leukemia (CML) patients in deep molecular response do not lose the major molecular response (MMR) after stopping treatment with tyrosine kinase inhibitors (TKI). This strategy is safe in clinical trials, but its applicability in the real-life setting remains unsettled. We describe the outcomes after TKI discontinuation in a nationwide series of 236 CML patients. Median follow-up from treatment discontinuation was 21.5 months and 5 patients died from CML-unrelated causes. TKI therapy was reinitiated due to MMR loss (n = 52), increase ≥ 1 log in BCR-ABL transcript level without losing MMR (n = 12), patient preference (n = 2), and withdrawal syndrome (n = 1). Treatment-free remission rate at 4 years was 64% (95% confidence interval, CI: 55%–72%). Cumulative incidence of molecular recurrence at 3 years was 33% (95% CI: 26%–38%). TKI treatment for n = 196), MR4 (n = 15), MMR (n = 14), complete cytogenetic response (n = 10), and other (n = 1). A significant increase in Hb and cholesterol levels was observed after imatinib withdrawal. Our results demonstrate that TKI treatment discontinuation is feasible in real-life clinical practice.

Bosutinib is a second-generation tyrosine kinase inhibitor (2GTKI) approved at 400 mg once daily (QD) as first-line therapy in patients with chronic myeloid leukemia (CML) patients and at 500 mg QD in patients who are resistant to or intolerant of prior therapy. In clinical practice, bosutinib is often given to patients who have failed imatinib, nilotinib, and dasatinib (i.e., as fourth-line treatment), despite the limited data on its clinical benefit in this setting. We have retrospectively evaluated the results of bosutinib in a series of 62 CML patients who have failed to prior treatment with all three, imatinib, nilotinib, and dasatinib. Median time on TKI treatment before bosutinib start was 105 (9–163) months, and median duration on bosutinib was 9 months (1–30). Overall, probabilities to achieve complete cytogenetic response (CCyR) and major molecular response (MMR) were 25% and 24% respectively. After a median follow-up period of 14 months, the event-free survival and progression-free survival were 68 and 85%, respectively. Sixty-four percent of patients in CCyR at the time of bosutinib start were able to achieve MMR. In contrast, patients without CCyR, probabilities to obtain CCyR and MMR were 25% and 14%. Bosutinib was well tolerated in this heavily pretreated patients’ cohort. Pleural effusions and diarrhea were the most frequent grade II–IV side effects, leading to treatment discontinuation in 16% of patients. Bosutinib is an effective treatment option for patients who have failed previous 2GTKIs due to intolerance. However, efficacy seems to be related to the molecular response that the patient achieved prior to bosutinib.

Correction to: J Cancer Res Clin Oncol (2017) 143:2059-2066 DOI 10.1007/s00432-017-2445-z.

Purpose This study was aimed to analyze the association of very early molecular response to nilotinib with the achievement of deep molecular response (MR4) at 18 months. We hypothesized that the BCR-ABL1 levels during the first 3 months of therapy, and the kinetics of their descent in this period, could be predictive of deep molecular response thereafter. Methods This substudy of the ENEST1st trial included 60 patients with chronic myeloid leukemia in chronic phase treated with front-line nilotinib, and BCR-ABL1IS levels were measured using GUS as the control gene. The analysis included seven time points during the first trimester of treatment (baseline and fortnightly thereafter). Results The rates of MMR at 12 months, and of MR4 at 18 months (primary variable of the study), were 70 and 41%, respectively, similar to those obtained in the core study. BCR-ABL1IS ≤10% was achieved at 1, 1.5, 2 and 3 months in 50, 70, 83 and 93% of the patients, respectively. The observed shape of the BCR-ABL1IS descent was biphasic, with a faster slope during the first trimester and a median halving time (HT) of 11 days, the shortest reported in the literature. An HT ≤13 days was predictive of MMR at 12 months and MR4 at 18 months. Conclusions The association of a shorter HT with response provides a rationale for exploring very early kinetics patterns in all patients treated with potent TKIs such as nilotinib.

The association between seven polymorphisms in the genes hOCT1 and MDR1, encoding for imatinib transporter proteins, and the response to imatinib 400 mg/daily was investigated in 65 patients newly diagnosed with chronic-phase chronic myeloid leukemia. The AA genotype at the rs6935207 hOCT1 polymorphic locus was not detected in patients with inadequate response to imatinib. The CC genotype at the rs1045642 (C3435T) MDR1 locus was associated with primary failure, whereas a T allele at the rs2032582 (G2677T/A) MDR1 locus seemed to protect from primary failure. Beside, the MDR1 haplotype 1236T-2677G-3435C was more frequently found in patients primarily resistant to imatinib.

Introduction: Over half of patients with chronic myeloid leukemia (CML) in sustained deep molecular remission do not lose the major molecular response (MMR) after stopping treatment with tyrosine kinase inhibitors (TKI). This strategy is safe in controlled clinical trials, but there is scarce information on its applicability in the real-life setting. We aimed to assess if treatment cessation was feasible in clinical practice in a large nationwide series of CML patients from Spain. Methods: This retrospective study comprised a series of 236 patients in chronic-phase CML who discontinued TKI treatment outside of clinical trials between April 2009 and February 2018 in 33 Spanish institutions. Inclusion criteria were: a) TKI treatment duration >3 years; b) sustained MR4.5 in >4 consecutive determinations (one single point in MR4 was acceptable) during >2 years; c) molecular monitoring in a reference laboratory expressing the results on the International Scale (IS). Patients who had undergone allogeneic hematopoietic stem-cell transplantation were excluded. Molecular relapse was defined as consecutively detectable BCR-ABL1 transcripts showing a ≥1 log increase or loss of MMR in any single sample. Treatment-free remission (TFR) was estimated by the method of Kaplan-Meier and defined as the time from TKI discontinuation to the date of restarting therapy for any reason or, if treatment was not restarted, the date of last contact. Incidence of molecular relapse was calculated using the cumulative incidence function with resumption of TKI treatment in the absence of molecular relapse and death in MMR as competing events. Analysis of factors predicting molecular relapse was done by the method of Fine and Gray. Results: Table 1 shows the main characteristics of the series. Median follow-up from treatment discontinuation was 21.5 months, and 5 patients died in MMR due to CML unrelated causes. TKI therapy was reinitiated due to molecular relapse (MMR loss: n=52, increase >1 log in BCR-ABL transcript level at two consecutive assessments without losing MMR: n=12), patient preference (n=2), and severe withdrawal syndrome (n=1). One additional patient lost MMR after 20 months from treatment cessation but decided not to be retreated, with spontaneous recovery of MMR. The probability of TFR at 4 years was 64% (95% Confidence Interval [CI]: 55%-72%)(Figure 1). The cumulative incidence of molecular recurrence was 33% (95% CI: 26%-38%) at 3 years (Figure 2). Forty-nine relapses (75% of total) occurred in the first 6 months. The latest MMR loss was detected 30 months after treatment stop. One patient restarted treatment 44 months after TKI discontinuation due to ≥1 log increase in BCR-ABL1 transcripts in two consecutive samples without losing MMR. In univariate analysis, duration of TKI treatment of less than 5 years (P=0.005) and time in RM4.5 shorter than 4 years before TKI discontinuation (P=0.003) were both significantly associated with a higher incidence of molecular recurrence. No patient progressed to the advanced phases of CML. At the time of restarting treatment, the median BCR-ABL1 IS was 0.3%, with this value being >5% in only 7 instances. Most patients (81%) received the same TKI that they were taking before the trial of treatment cessation. Median follow-up after treatment resumption was 20 months. Among the 64 patients who restarted treatment due to molecular relapse, 46 of 52 cases regained MMR after a median time of 3 months, and 47 of 64 regained MR4.5 after a median time of 5 months. Response status at last control was: MR4.5 (n=196), MR4 (n=15), MMR (n=14), complete cytogenetic response (n=10), and other (n=1). Fifty-one patients (22%) developed musculoskeletal or joint pain after treatment cessation. In patients stopping imatinib, a significant increase in Hb levels, leukocyte counts, total lymphocyte counts, platelet counts, and cholesterol levels was observed. At 6 months, an increase in Hb level >2 g/dL was observed in 47% of patients with anemia. By contrast, nilotinib discontinuation was not followed by any relevant change in laboratory values. Conclusions: Our results confirm that treatment discontinuation is feasible and safe in clinical practice in Spain. Duration of TKI treatment of less than 5 years and a time in RM4.5 shorter than 4 years before TKI discontinuation were significantly associated with a higher incidence of molecular recurrence. Disclosures Hernandez Boluda: Incyte: Consultancy; Novartis: Consultancy. García Gutiérrez:Incyte: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; BMS: Honoraria, Research Funding; Novartis: Honoraria, Research Funding. Ferrer Marin:Incyte: Consultancy; Novartis: Consultancy, Research Funding. Cervantes:Celgene: Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Hospital Clinic Barcelona: Employment.

Conventional treatment of myelofibrosis includes a wait-and-see approach for asymptomatic patients, the use of oral cytolytic drugs such as hydroxyurea for the hyperproliferative forms of the disease, androgens or erythropoietin for anemia, and splenectomy in selected patients. Although these treatment modalities can improve quality of life, many patients do not respond, and the impact on survival is scant. This fact has stimulated the search for newer therapies for the disease. Antiangiogenic and immunomodulatory drugs such as thalidomide and lenalidomide have shown efficacy against anemia and thrombocytopenia but have frequent side effects. The combination of low-dose thalidomide with prednisone can also be effective and has a better tolerability. The therapeutic role of imatinib is limited, while tipifarnib, a farnesyltransferase inhibitor, has a modest effect in anemia and splenomegaly. Allogeneic stem cell transplantation (alloSCT) is the only curative therapy of myelofibrosis. AlloSCT with a standard conditioning regimen has an associated mortality rate of 30% and is indicated in younger patients with high-risk disease or resistance to conventional treatment. Because of its low mortality and curative potential, reduced-intensity conditioning alloSCT is being used in patients aged 45-70 years with high- or intermediate-risk myelofibrosis or resistance to treatment. Autologous SCT can be a palliative measure in patients without a suitable donor. The efficacy in myelofibrosis of newer immunomodulatory drugs, including pomalidomide, proteasome inhibitors, hypomethylating agents, and especially, Janus kinase 2 inhibitors, is currently being evaluated.

El sindrome de POEMS (polineuropatia, organomegalia, endocrinopatia, banda monoclonal y alteraciones cutaneas) es una entidad infrecuente, que se caracteriza por una proliferacion clonal de celulas plasmaticas que da lugar a un componente monoclonal, por lo general poco abundante y con restriccion de la cadena lambda. Clinicamente cursa con afectacion multisistemica, dentro de la cual predomina la polineuropatia periferica. No existe un tratamiento especifico para esta enfermedad. Se presentan 4 casos de sindrome de POEMS tratados mediante trasplante autologo de progenitors hematopoyeticos en nuestro centro. Todos ellos mejoraron de sus manifestaciones neurologicas y sistemicas, al tiempo que presentaron una disminucion o desaparicion del componente monoclonal y de las lesiones oseas. En conclusion, el trasplante autologo de progenitores hematopoyeticos constituye una opcion terapeutica util en el sindrome de POEMS.

Imatinib is currently the treatment of choice in chronic myeloid leukemia. The use of this drug is safe, although some cases of imatinib-induced toxic hepatitis have been reported. We present 2 patients treated with this drug who developed acute anicteric hepatitis months after starting treatment. We also review 20 reports of individual cases to characterize imatinib-induced hepatitis. Imatinib-induced hepatitis has a variable latency period, frequently of several months. Half of the patients develop anicteric hepatitis and the clinical course is generally benign. A distinguishing feature of this entity is a transitory increase in transaminase levels in patients diagnosed with hepatitis in the weeks after treatment withdrawal. Resumption of imatinib use provokes hepatitis recurrence, which can be avoided by simultaneous prednisone administration.

A 73-year-old woman complaining of bone pain and weight loss was suspected to have a malignant disease, and extensive laboratory investigations were carried out. She was diagnosed with multiple myeloma; however, because of the finding of extremely high serum levels of CA125 and CA15.3 and focal liver lesions, a concomitant solid tumor was suspected, which was then excluded with the appropriate tests, including an ultrasound-guided liver biopsy. While being diagnosed, the patient developed a rapidly evolving plasma cell leukemia with a simultaneous increase in CA125 and CA15.3. After treatment with cyclophosphamide and dexamethasone, the peripheral blood plasma cells disappeared and there was a dramatic decrease in the CA125 and CA15.3 tumor markers. High levels of the latter can be observed in patients with aggressive plasma cell dyscrasias, an observation that is crucial in order to avoid unnecessary tests that can result in treatment delay.

Darbepoetin-alpha, a novel hyperglycosylated erythropoiesis-stimulating protein, was administered to 20 patients with myelofibrosis with myeloid metaplasia and anaemia. The initial weekly dose, 150 mug, was increased to 300 mug when no response was observed after 4-8 weeks. Eight patients (40%) responded to treatment, including six complete and two partial responses, and five maintained their response at a median follow-up of 12 months (range 4-22). Univariate analysis indicated that older age was the only factor associated with a favourable response to treatment (P = 0.006). None of the patients with appropriate serum erythropoietin levels responded. Treatment was usually well tolerated.

BACKGROUND: Despite the excellent prognostic of chronic myeloid leukemia (CML) patients since the introduction of tyrosine kinase inhibitors (TKIs), approximately 50% of patients that are treated with TKIs will discontinue first line treatment due to lack of efficacy or intolerance. Once patients need a second line treatment, a considerable proportion of patients will need third or even fourth line therapy during further evolution. At this moment, there is a lack of data about real benefit of this group of patients. We have recently published our experience of 30 CML patients treated with bosutinib in 4th line. We present an update of the study where we have increased the number of patients, and the follow-up. The aim of this study is to present safety and efficacy data CML chronic phase patients treated with bosutinib in 4th line. METHODS: We have collected data from 59 CML patients treated with bosutinib in 4th line after resistance or intolerance to IM, NI and DA. 51 patients have been treated under the Spanish compassionate use program (36 centers) and 10 patients were treated in a single institution from United Kingdom. Median age of patients at diagnosis was 53 years. The percentage of low, intermediate and high risk Sokal groups were 47%, 37% and 16%. Median time TKIs exposure before bosutinib was 9 years. The most common indication (30/59) was intolerant to DA and NI. Patients' dispositions and main line characteristics are shown in table 1. RESULTS: Median follow-up was 14.3 months. All patients started bosutinib at 500mg/d, median dose of was 450mg/d. Overall probabilities to either achieve or maintain previous response were 96% (57/59), 62% (37/59), 40% (24/59) and 17% (10/59) for complete hematological response (CHR), complete cytogenetic response (CCyR), major molecular response (MMR) and MR4.5 respectively. However, probabilities to obtain responses (in patients without response evaluated at baseline) were 27% (7/26), 26% (12/45) and 12% (7/55) for CCyR, MMR and MR4.5. As expected, probabilities to obtain CCyR were lower for patients resistant to DA and NI patients than for patients intolerant to DA and NI (8% VS 44%). Event free survival (EFS) and progression free survival (PFS) probabilities were 50% and 83% by 27 month. Treatment was discontinued in 20/58 (34%), most frequent reasons being adverse events 9/59(15%), lack of efficacy 5/59 (8.5%), disease progression 2/59 (3.4%) and death 1/59 (1.7%). Two patients discontinued due to stem cell transplantation. The adverse events that led to treatment discontinuation were pleural effusion (3), diarrhea (2), rash, renal impairment, auricular fibrillation and liver enzyme elevation one patient each. Overall, bosutinib was well tolerated. Grade 3-4 hematological toxicities were 3%, 6% and 6% for anemia, thromboctytopenia and neutropenia. Most common non hematological side effects were diarrhea (39%, nauseas 13% and liver alterations 14% and pleural effusion 14%. CONCLUSIONS: Little is known about the therapeutic role of Bosutinib in 4th line. The series presented here is, to our knowledge, the largest being presented. Bosutinib seems to be an appropriate treatment option for patients resistant or intolerant to three prior TKIs. | | IM+NI-I+DA-R (N=4) | IM+NI-R+DA-R (N=18) | IM+NI-I+DA-I (N=30) | IM+NI-R+DA-I (N=7) | Total (N=59) | | ------------------------------------------------ | ----------------------- | ------------------------ | ----------------------- | ------------------------ | ------------------------- | ------------------------- | | Sex, N (%) Male | 2 (50) | 11 (61.1) | 16 (53.3) | 2 (28.6) | 31 (52.5) | | Median age of diagnosis, yr (range) | 57.32 (50-64) | 49.19 (23-73) | 54.95 (21-89) | 48.87 (26-68) | 53.15 (21-89) | | Median age of Bosutinib initiation, yr (range) | 69.13 (61-70) | 62.27 (39-79) | 64.85 (25-90) | 64.79(35-74) | 63.7 (25-9) | | Median follow up, months (range) | 18.5(7.8-34.1) | 8.4(1.22-36.1) | 16.3(0.5-34.7) | 23.4(3.3-28.9) | 14.3(0.7-36.1) | | SOKAL Index at diagnosis, N (%) | High | 2(50.0) | 4 (23.5) | 1 (4.3) | 1 (20) | 8 (16.3) | | Intermediate | 1 (25.0) | 5 (29.4) | 10(43.5) | 2 (40) | 18 (36.7) | | Low | 1 (25.0) | 8 (47.1) | 12 (52.2) | 2 (40) | 23 (46.9) | | Median Time from first TKI to BOS, (yr, range) | 10.3 (4.8-11.9) | 9.3 (2.0-11.4) | 8.8 (0.7-13.6) | 8.2 (5.1-12.3) | 8.8 (0.7-13.6) | | Median duration of prior therapy, months (range) | Imatinib | 38.8 (11.8-69.8) | 32.6 (6.3-96.8) | 26.2 (1.6-102.6) | 23.1 (8.3-66.8) | 28.8 (1.6-102.6) | | Dasatinib | 21.5 (12.6-75) | 21.8 (7.7-69) | 31.4 (0.4-87.1) | 23.7 (10.3-53.6) | 23.44 (0.4-87.1) | | Nilotinib | 19.1 (2.1-46.2) | 16.7 (5-65.6) | 8.9 (0.2-58.5) | 30.9 (6.9-49.3) | 14.3 (0.2-65.6) | * BOS: bosutinib, IM, imatinib; DA, dasatinib; NI, nilotinib, I: Intolerance, R: Resistant, Yr: year Table 1. Disclosures Garcia-Gutierrez: Ariad: Consultancy; Pfizer: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Novartis: Consultancy, Honoraria. Milojkovic: Novartis: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Ariad: Consultancy, Honoraria; BMS: Consultancy, Honoraria. Boque: Novartis: Honoraria; BMS: Honoraria; Celgene: Honoraria. Casado: Novartis: Honoraria, Research Funding; BMS: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; Roche: Honoraria, Research Funding. Jimenez: Pfizer: Consultancy, Honoraria. Giraldo: Pfizer: Consultancy. Steegmann: Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau; BMS: Consultancy, Honoraria, Research Funding, Speakers Bureau; Pfizer: Consultancy, Honoraria, Research Funding, Speakers Bureau; Ariad: Consultancy, Honoraria, Research Funding, Speakers Bureau.

POEMS (polyneuropathy, organomegaly, endocrinopathy, M protein, skin changes) syndrome is a rare disorder characterized by a clonal plasma cell proliferation with a monoclonal protein typically small and lambda restricted. Clinically, this syndrome is a multisystemic disease whose major clinical feature is a peripheral polyneuropathy. A specific treatment for this disease does not exist. We report 4 patients with POEMS syndrome treated with an autologous haematopoietic stem cell transplantation in our centre. All patients had an improvement in neurologic symptoms and other manifestations of the syndrome. The monoclonal component and bone lesions decreased or disappeared. In conclusion, autologous haematopoietic stem cell transplantation is an effective therapy in patients with POEMS syndrome.

Imatinib is currently the treatment of choice in chronic myeloid leukemia. The use of this drug is safe, although some cases of imatinib-induced toxic hepatitis have been reported. We present 2 patients treated with this drug who developed acute anicteric hepatitis months after starting treatment. We also review 20 reports of individual cases to characterize imatinib-induced hepatitis. Imatinib-induced hepatitis has a variable latency period, frequently of several months. Half of the patients develop anicteric hepatitis and the clinical course is generally benign. A distinguishing feature of this entity is a transitory increase in transaminase levels in patients diagnosed with hepatitis in the weeks after treatment withdrawal. Resumption of imatinib use provokes hepatitis recurrence, which can be avoided by simultaneous prednisone administration.

Objectives To analyze the molecular response during the first trimester of nilotinib therapy in newly diagnosed CML-CP patients. Hypothesis The values of BCR-ABL ratios during the first trimester of nilotinib treatment, and the kinetic of their descent, could be predictive of molecular response thereafter. Patients ENEST1st (NCT01061177) is an open-label study of nilotinib 300 mg twice daily in adults with newly diagnosed BCR-ABL+ CML-CP. Imatinib pretreatment was not allowed. Methods BCR-ABLIS and BCR-ABL/GUS ratios were measured previously to nilotinib, and fortnightly thereafter until the 3rd month (m), and at 6, 12 and 18 m. Sokal, Euro and Eutos scores were calculated with data at diagnosis. BCR-ABL values were centrally measured in an ELN-EUTOS certified laboratory. Molecular response was classified by ELN2013 recommendations. As the linearity of values of BCR-ABL using ABL as control is questionable, when ratios are higher than 10%, only baseline BCR-ABL/GUS ratios were used when analyzing the molecular response using GUS as control. The kinetic of the descent was calculated using the ratio of a given time compared with that of an earlier time, and measuring slopes. Logistic regressions and ROC analysis have been used, calculating positive and negative predictive values (PPV and NPV) Results 61 patients were included. 1 patient was excluded of the analysis because of lack of molecular data (baseline). Out of 60 patients, 10 abandoned during the first 18 m because of AE’ s. Those patients have been classified as non-responders after the time they went off-study. Risk distribution: Sokal (L, I, H): 57%, 32%, 11.7% Euro: 52%, 45%, 3%) Eutos (L, H): 92%, 8%). Outcomes and Molecular response: No patient died or transformed during the follow-up. MR4.5 at 18 M has been obtained in 30% of the patients. The ELN 2013 molecular milestones for optimal response at 3,6,12 and thereafter were obtained in 97%, 93%, 83%, and 70%, respectively.(Table) Predictive variables of response: (Table). Major molecular response (²0.1%) (BCR-ABL/ABL, BCR-ABL/GUS). At 3MBaseline BCR-ABL/GUS ratios were significantly different between responders and non-responders (22,1±23,1 vs 41,5± 38,1, p=0.05). For both control genes, the multivariate analysis disclosed that the independent and significant variable was the ratio at 45d. The ROC analysis disclosed a cut-off of 3.28 (PPV: 83% NPV: 80%). [OR: 20(4.4- 90) p Discussion Our results show that, in newly diagnosed patients, nilotinib obtained responses very quickly, and the proportions of patients having an optimal ELN2013 response at 3M (BCR-ABLIS² 10%), and at 6M (BCR-ABL IS ² 1%) were 97% and 93%. For obtaining a MMR at 3M, the only significant cut-off was at 45 d. For subsequent MMR, the only independent variable was the ratio at the most immediate earlier point. Besides, our results show a similar proportion of responses when using GUS as control gene, and similar predictive cut-offs in the ROC analysis of MMR at 3 and 6 M. Nilotinib treatment obtained 30% of MR4.5 at 18M. Ratios at 1M, 1.5 M, and 2 M were significantly associated with this response, but the only independent variable was the BCR-ABL ratio at 2M. At 2 M, having a ratio higher than 1.52 % will be linked with a 91% probability of not obtaining a MR4.5 at 18 M. Disclosures: Steegmann: Pfizer: Honoraria, Research Funding, Speakers Bureau; BMS: Honoraria, Research Funding, Speakers Bureau; Novartis: Honoraria, Research Funding, Speakers Bureau. Casado Montero:Pfizer: Honoraria, Research Funding, Speakers Bureau; BMS: Honoraria, Research Funding, Speakers Bureau; Novartis: Honoraria, Research Funding, Speakers Bureau. Echeveste:Celgene: Consultancy; Novartis: Consultancy. Garcia-Gutierrez:Novartis: Membership on an entity’s Board of Directors or advisory committees; BMS: Membership on an entity’s Board of Directors or advisory committees; Pfizer: Membership on an entity’s Board of Directors or advisory committees. Ruiz:Novartis: Employment. Walasek:Novartis: Employment.