ALBERT

Description: According to the World Health Organization (WHO) 2008/2016 criteria for classification of myeloid neoplasms, a platelet (PLT) count ≥ 450X109/l, thus reduced from the previous WHO 2001 level ≥ 600 x 109/l, was considered the new PLT threshold for the diagnosis of Essential Thrombocythemia (ET). Aim of the study was to validate in a setting of current clinical practice this important diagnostic change and compare clinical and hematological features at diagnosis and during follow-up of patients with PLT ≥600 x 109/l versus patients with PLT 〈 600 x 109/l. We retrospectively analyzed data from 264 patients with ET according to WHO 2008/2016 criteria, enrolled in our center from 1/2008 to 12/2017. Patients were divided into Group A (G-A) (PLT ≥600 x 109/l at diagnosis) (199 patients - 75.4%) and Group B (G-B) (PLT ≥ 450 x 109/l 〈 600 x 109/l at diagnosis) (65 patients - 24.6%) and compared for clinical features at the onset, clinical course and follow-up. Main features and commonly recognized pro-thrombotic risk factors at diagnosis of the entire cohort as well as of G-A and G-B are reported in the Table 1. Among clinical features, only the median value of leukocytes was significantly higher in G- A [9.1 x 109/l, interquartile range (IQR) 7.8-10.3 vs 7.4 x 109/l, IQR 6.0-9.6; p = 0.001]. Among pro-thrombotic risk factors, only the median cholesterol value was significantly lower in the G-A [187 mg/dl (IQR 164-220) vs 204 mg/dl (RIQ 177-238); p = 0.048]. Cytostatic treatment was administered in 175 patients (71.1%) of entire cohort at different intervals from diagnosis, with a significantly higher rate in patients of G-A (76.9% versus 49.2%, p 1.000 x 109/l, highlights how thrombotic risk is unrelated to PLT value and leads to consider the administration of adequate cytostatic therapy even in patients with relatively lower PLT count at diagnosis. Disclosures Breccia: Novartis: Honoraria; Pfizer: Honoraria; Incyte: Honoraria; BMS: Honoraria. Foà:INCYTE: Other: ADVISORY BOARD; JANSSEN: Other: ADVISORY BOARD, Speakers Bureau; GILEAD: Speakers Bureau; CELTRION: Other: ADVISORY BOARD; ABBVIE: Other: ADVISORY BOARD, Speakers Bureau; CELGENE: Other: ADVISORY BOARD, Speakers Bureau; AMGEN: Other: ADVISORY BOARD; ROCHE: Other: ADVISORY BOARD, Speakers Bureau; NOVARTIS: Speakers Bureau.

Description: Background Bosutinib is a 2nd generation tyrosine-kinase inhibitor (TKI) active in Chronic Myeloid Leukemia (CML) patients resistant or intolerant to frontline imatinib, dasatinib or nilotinib; the favourable toxicity profile makes bosutinib potentially useful in elderly patients, but at present there are no data in unselected cohorts of these subjects. Aim To highlight this issue, a real-life cohort of 91 patients followed in 21 Italian Centers and treated with bosutinib when aged 〉 65 years was retrospectively evaluated. Patients The main clinical features of the whole cohort at diagnosis and at baseline of bosutinib treatment are reported in the Table; all patients were in CP when bosutinib was started. Median interval from diagnosis to bosutinib treatment was 49.7 months [interquartile range (IQR) 14.2 - 117.5]. Results Starting dose of bosutinib was 500 mg/day in 20 patients (22.0%), 400 mg/day in 7 patients (7.7%), 300 mg/day in 28 patients (30.8%), 200 mg/day in 34 patients (37.3%) and 100 mg/day in 2 patients (2.2%), respectively. After a median period of treatment of 18.1 months (IQR 9.4 - 27.7) all patients were evaluable for toxicity; on the whole, all grade hematological and extra-hematological toxicities were reported in 12/91 (13.1%) and 45/91 (49.4%) patients, respectively. A grade 3 - 4 hematological toxicity occurred in 5/91 patients (5.4%); a grade 3 - 4 extra-hematological toxicity occurred in 16/91 patients (17.5%). Overall, 46 patients (50.5%) never discontinued bosutinib: a temporary discontinuation 〈 6 weeks was needed in 19 patients (20.9%) and a temporary discontinuation 〉 6 weeks in 2 patients (2.2%). A permanent bosutinib discontinuation was needed in the remaining 24 patients (26.4%): in particular, 11 patients (12.1%) permanently discontinued bosutinib due to toxicity (skin rash in 3 cases, gastro-intestinal toxicity in 3 cases, pleural effusion in 2 cases, transaminitis, QTc prolongation and myalgia in 1 case each), 6 patients (6.6%) due to resistance and 7 patients (7.7%) due to other reasons (unrelated death in 6 cases and patient decision in 1 case). As to response, 5 patients (5.5%) were considered too early for assessment (〈 3 months of treatment); among the 86 patients evaluable for response, 11 patients (12.7%) did not have any response (including 6 patients who discontinued bosutinib for early toxicity), 4 (4.6%) achieved hematological response only, and 71 (82.5%) achieved Cytogenetic Response (CyR) (Major CyR in 4, Complete CyR in 67). Among the 67 patients in Complete CyR, 58 (67.4% of all 86 evaluable patients) also achieved Molecular Response (MR) [Major MR (MR 3.0) in 19 (22.1%), Deep MR (MR 4.0/4.5) in 39 (45.3%)]. The 3-year Overall Survival and Event-Free Survival of the whole cohort of patients from bosutinib start were 83.0% (CI95% 71.6 - 94.4) (Figure 1) and 59.5% (CI95% 39.9 - 72.1), respectively. Conclusions Our real-life data show that bosutinib is effective, even if initial doses in many cases were lower than recommended, with a favourable safety profile also in elderly patients with important comorbidities resistant/intolerant to previous TKI treatments,: as a consequence, it could play a significant role in the current clinical practise for these frail patients. Disclosures Latagliata: Celgene: Honoraria; Janssen: Honoraria; Novartis: Honoraria; Pfizer: Honoraria. Trawinska:Novartis: Consultancy, Honoraria. Annunziata:Pfizer: Consultancy; Incyte: Consultancy; Novartis: Consultancy. Elena:Novartis: Consultancy; Pfizer: Consultancy. Crugnola:Incyte: Honoraria; Novartis: Honoraria. Bonifacio:Novartis: Honoraria; Amgen: Honoraria; Pfizer: Honoraria; Incyte: Honoraria; BMS: Honoraria. Sgherza:Incyte: Honoraria; Pfizer: Honoraria; BMS: Honoraria; Novartis: Honoraria. Iurlo:Pfizer: Other: Speaker Honoraria; Incyte: Other: Speaker Honoraria; Novartis: Other: Speaker Honoraria. Breccia:Celgene: Honoraria; Incyte: Honoraria; Novartis: Honoraria; BMS: Honoraria; Pfizer: Honoraria.

Description: Dasatinib (DAS) has been licensed for first line treatment of patients (pts) with Chronic Myeloid Leukemia (CML): however, in the current clinical practice, DAS is often considered too toxic for the treatment of elderly CML patient. In particular, no data are available in very elderly CML pts as to toxicity and efficacy. To address this issue, we evaluated a "real-life" cohort of 39 CML pts in chronic phase aged 〉 75 years and treated with frontline DAS in 20 Italian Centers from 6/2012 to 10/2017. Main clinical features at diagnosis are reported in the Table 1. Overall, 23/39 pts (58.9%) had ≥ 2 comorbidities requiring concomitant therapies: according to ECOG scale, performance status at baseline was 0 - 1 in 34 pts (87.2%) and 2 in 5 pts (12.8%). Median interval from diagnosis to DAS therapy was 0.8 months (IQR 0.5 - 1.4). Daily DAS starting dose was 100 mg in 30 pts (76.9%), 80 mg in 1 pts (2.6%) and 50 mg in 8 pts (20.5%), respectively. All pts were evaluable for toxicity and efficacy; on the whole, grade 3/4 hematological and extra-hematological toxicities were detected in 6 (15.4%) and 11 (28.2%) pts, respectively. DAS therapy was permanently discontinued in 9 pts (23.0%) due to toxicity (3 pts in the first 12-month period of treatment and 6 beyond). Pleural effusions of all WHO grades occurred in 12 pts (30.7%) after a median period of DAS treatment of 16.3 months (IQR 2.2 - 31.8): in 4 of them pleural effusion occurred during the first 6-month period of treatment. Overall, 36/39 patients (92.3%) achieved at any time complete cytogenetic response (CCyR), 30/39 (76.9%) major molecular response (MR 3.0) and 16/39 (41.0%) deep molecular response (MR 4.0/4.5). Only 1 patient (2.6%) evolved in a blastic phase after 13 months from DAS initiation. After a median period of 27.8 months (IQR 19.1 - 37.5), 5 patients died (1 from blastic phase and 4 from unrelated causes): cumulative event-free survival and overall survival at 36 months were 63.2% (95%CI 45.2 - 81.2) and 85.3% (95%CI 73.3 - 97.3), respectively (Figures 1 and 2). In conclusion, these data indicate that DAS therapy may have a role also in the treatment of patients aged 〉 75 years, being effective as in younger subjects and having an acceptable safety profile. Disclosures Gugliotta: Novartis: Honoraria; Pfizer: Honoraria; Bristol-Myers Squibb: Honoraria; Incyte: Honoraria. Abruzzese:Ariad: Consultancy; BMS: Consultancy; Novartis: Research Funding; Pfizer: Consultancy. Breccia:Pfizer: Honoraria; BMS: Honoraria; Novartis: Honoraria; Incyte: Honoraria.

Description: Current treatment with Tyrosine-Kinase Inhibitors (TKI) has profoundly changed long-term prognosis of newly diagnosed Chronic Myeloid Leukemia (CML). However, the true disease/patient status at different time-points is still based on few data from controlled clinical studies (mainly based on "cumulative incidence" more than "effective situation" of any single patient at any single time from TKI start) and is still unclear in the real-life setting without selection criteria. In order to give an effective picture of their 5-year status, all consecutive CML patients newly diagnosed at our Institute until 6/2012 (i.e. with a minimum observation period of 5 years) and treated frontline with any TKI at any dosage in both controlled clinical trials or current clinical practice were retrospectively evaluated. On the whole, 259 patients, treated with imatinib (219) or 2nd generation TKI (2-TKI) (35 with nilotinib and 5 with dasatinib), were collected: the main features at diagnosis of the entire cohort and according to TKI are reported in the Table 1, without differences between the 2 groups. In the imatinib group, 13/219 patients (6%) received a reduced starting dose (〈 400 mg/day), while all patients in the 2-TKI group started initial standard doses. At the 5-year evaluation, 227 pazienti (87.6%) were alive, 16 died (6.2%) and 16 (6.2%) were lost to follow-up. Among the 227 patients alive, 176 (67.9% of the entire cohort) were in Complete Cytogenetic Response (CCyR), 163 (62.9% of the entire cohort) were in Major Molecular Response (MMolR) and 121 (46.7% of the entire cohort) were in Deep Molecular Response (DMR). The remaining 51 patients alive at the 5th year (19.7% of the entire cohort) were in 2nd or subsequent line of treatment, due to intolerance in 13 cases (25.5%) or primary/secondary resistance in 38 (74.5%). Among the 16 deaths, 5 (1.9% of the entire cohort) were CML-related and 11 (4.3% of the entire cohort) were CML unrelated. Among the 16 patients lost to follow-up, 8 (3.1% of the entire cohort) were in response to 1st line treatment and 8 (3.1% of the entire cohort) were in 2nd line/resistant disease at the last visit. Six patients (2.3%) evolved in blastic phase and 8 (3.1%) developped a 2nd neoplasia. In the group treated frontline with 2-TKI there was a higher rate of patients alive in MMolR (p=0.038) but not in DMolR (p=0.137), with a lower rate of primary/secondary resistance (p=0.048) but a higher incidence of intolerance (p=0.002) compared to patients treated frontline with imatinib (Table 2). Five-year cumulative overall survival (OS), progression-free survival (PFS) and event-free survival (EFS) of the entire cohort were 93.2% (IC 95% 90.2-96.2), 78.2% (IC95% 73.1-83.3) e 70.2% (IC95% 64.5 - 75.9), respectively. According to initial treatment, 5-year PFS was significantly better in the 2-TKI group (p=0.003), but no difference was observed between the 2 groups as to 5-year EFS (p=0.274) and 5-year OS (p=0.077). In conclusion, results achievable at 5 years with frontline TKI treatment in the current clinical practice are excellent, with at least two thirds of patients alive in MMolR and about half of patients also in DMolR under frontline approach: deaths CML-related in the first 5 years of treatment are very rare and less than 1 out 5 patients needs to change frontline approach for intolerance/resistance. The role of frontline 2-TKI in this real-life setting deserves further examinations in larger unselected cohorts at longer time-points. Disclosures Breccia: BMS: Honoraria; Novartis: Honoraria; Incyte: Honoraria; Pfizer: Honoraria. Foà:ROCHE: Other: ADVISORY BOARD, Speakers Bureau; CELGENE: Other: ADVISORY BOARD, Speakers Bureau; CELTRION: Other: ADVISORY BOARD; ABBVIE: Other: ADVISORY BOARD, Speakers Bureau; GILEAD: Speakers Bureau; NOVARTIS: Speakers Bureau; INCYTE: Other: ADVISORY BOARD; JANSSEN: Other: ADVISORY BOARD, Speakers Bureau; AMGEN: Other: ADVISORY BOARD.