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  • 1
    In: Blood, American Society of Hematology, Vol. 138, No. Supplement 1 ( 2021-11-05), p. 4875-4875
    Abstract: Patients with hematological malignancies (HM) undergoing hematopoietic stem cell transplantation (HSCT) have an increased vulnerability to SARS-Cov-2 (Sharma et al, Lancet Haematology 2020; Ljungman et al, Leukemia 2021), the reason why international guidelines strongly support the need for a protective vaccination for these subjects. The most relevant data currently available on the response to a complete anti-SARS-Cov-2 vaccination cycle in HM patients after HSCT refer to 314 patients reported in a Lithuanian national survey (Maneikis et al, Lancet Haematol 2021). In this study, the median titers of antibodies against SARS-Cov-2, determined 7-21 days after the second vaccination, were comparable to that of healthy controls (HC) in both autologous and allogeneic groups, with no patient found below the protective threshold of 50 arbitrary units (AU)/ml. Notably, the large majority of patients had received the transplant more than 1 year before vaccination. In a prospective, cohort study, we compared 114 patients, who had received an autologous or allogeneic HSCT at least three months before the first dose of vaccination, to 107 HC, matched for age and sex. Study population and HC received two doses of BNT162b2 anti-SARS-Cov-2 mRNA vaccine on days 1 and 21, between April and May 2021. Serological tests were performed by a commercially available immunoassay for the quantitative determination of anti-spike IgG antibodies to SARS-Cov-2. The cut-off for defining responders was 50 or greater AU/ml. Patients and HC samples were collected four weeks after the second dose of the vaccine. Table 1 reports the main clinical characteristics of patients and HC. Eighteen of 114 patients (16%) did not respond (24% in the allogeneic group, 6% in autologous recipients). Overall, median antibodies titers did not differ between HC and the entire cohort of transplanted patients, recipients of allogeneic HSCT, all patients responding to the vaccine or responders in the autologous subgroup (Figure 1A). All autologous HSCT recipients had significantly lower titers of antibodies than HC, while higher levels were found in responders who had received allogeneic HSCT (Figure 1A). Responders in the allogeneic subgroup showed antibodies titers significantly higher than responders in the autologous subgroup (Figure 1B). We further stratified patients in three groups, according to the time elapsed from transplant to vaccination: G1: & lt;1 year; G2:1-5 years; G3: & gt;5 years. Higher antibodies titers were observed in HC compared to all transplanted patients in G1 (Figure 1C), including both allogeneic (Figure 1D) and autologous (Figure 1E) HSCT recipients. No differences emerged in G2 between HC and all patients (Figure 1C), allogeneic (Figure 1D) or autologous (Figure 1E) HSCT recipients. Finally, no differences were found in G3 when comparing HC with all patients (Figure 1C) or allogeneic recipients (Figure 1D), whereas patients in the autologous subgroup showed significantly lower titers than HC (Figure 1E). Myeloma patients with controlled disease showed higher titers than patients with active disease (Figure 1F). According to median age, autologous HSCT recipients older than 57 years had significantly lower antibody levels than younger patients (Figure 1G). Autologous vs allogeneic HSCT, age of all patients and of allogeneic HSCT recipients, sex, type of allogeneic HSCT, conditioning regimen, age and sex of donor, occurrence of GVHD, disease type and single vs double autologous HSCT did not significantly impact on antibody levels (data not shown). No relevant side effects were recorded after vaccination. With a median follow up of 12 weeks, no case of COVID19 occurred among vaccinated patients. In our single center study, patients with a previous history of HSCT tolerated well BNT162b2 vaccine and mounted a potentially protective immune response in the majority of cases one month after two doses of vaccine. However, lack of response was not rare, especially in the allogeneic setting. The main factor associated with the quality of response was the time from HSCT, with lower responses within the first year from transplant and differences between autologous and allogeneic groups transplanted more than five years before vaccination. Here, a consolidated, complete immune reconstitution in allogeneic HSCT recipients, as well as age and a still active disease in the autologous setting, could have played opposite pivotal roles. Figure 1 Figure 1. Disclosures Delia: Gilead: Consultancy; Amgen: Consultancy; abbvie: Consultancy; Jazz pharmaceuticals: Consultancy.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2021
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  • 2
    In: Blood, American Society of Hematology, Vol. 136, No. Supplement 1 ( 2020-11-5), p. 8-9
    Abstract: Introduction. New guidelines for the management of dyslipidemia and lipid modification in order to reduce the risk of cardiovascular (CV) events have been recently published by the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS). New recommendations regarding the target value of plasma lipids in very high and high CV risk patients have been provided, in addition to an estimate of the CV risk with a new Systematic Coronary Risk Evaluation (SCORE) chart. Few data have been reported on the management of dyslipidemia in chronic myeloid leukemia (CML) patients treated with nilotinib, and the association with arterial occlusive events (AOEs). We therefore analyzed a large real-life cohort of Italian patients with CML treated with nilotinib outside of clinical trials and evaluated the association between AOEs and plasma lipoproteins levels; moreover, we estimated the prognostic value of the new SCORE chart to predict AOEs. The secondary endpoint was to report the management of dyslipidemia in the clinical practice. Methods. We identified 233 adult patients with CML who were treated in 20 Italian centers with nilotinib. All patients were stratified into low to moderate (SCORE ≤ 5%) or high to very high (SCORE risk & gt;5%) CV risk, according to the new version of the SCORE 2019. We recorded concentration levels of cholesterol, high-density lipoproteins (HDL), low-density lipoproteins (LDL) and triglycerides at diagnosis of CML, before starting ponatinib and therefore after 3, 6 and 12 months of treatment. All AOEs (cerebrovascular, peripheral vascular and CV events excluding hypertension) were considered. Results. The median age was 50 years (range 20-88) and the Sokal score was intermediate-high in 45.5% of patients. The median follow-up was 5 years (range 3.4-10.5). Nilotinib was administered as first line of therapy in (72%) of cases or second or subsequent lines of treatment for inefficacy (20.9%) or intolerance (7.1%). At baseline, nilotinib was administered at the following doses: 800 mg/day in 9.3% of patients, 600 mg/day in 87% of patients, 400 mg/day in 3.1% of patients and 300mg in 0.6% of patients, respectively. The median time of drug exposure was 60 months (range 2-155). The 48-month cumulative incidence rate of AOEs was 14.1±2.7%. Patients with cholesterol plasma levels & gt; 200 mg/dL and LDL & gt;70 mg/dL at baseline and 3 months after starting nilotinib, showed a significantly higher incidence of AOEs (24.5±7.3% vs 11±2.7%, P=0.02 and 22.3±4.9% vs 5.9±2.6, P=0.003, respectively) Figure 1. Patients with triglycerides levels & gt; 200 mg/dL 3 months after starting nilotinib, showed a significantly higher incidence of AOEs (56±20.5% vs 13.3±2.7%, P=0.011) Patients belonging to the high and very high SCORE risk group showed a significant increase of AOEs (32.8.1±9% vs. 9±1%±2.6%, p=0.001). In multivariate analysis, statistical significance of cholesterol plasma levels & gt; 200 mg/dL and LDL & gt;70 mg/dL after 3 months and high-very-high SCORE was maintained (P=0.018, HR=3.4, 95% CI=1.2-9.4 and P=0.004, HR=3.5, 95% CI=1.5-8.2, respectively). Overall, 46 patients (20.5%) presented dyslipidemia at CML diagnosis and 65 (29%) at the start of treatment with nilotinib. Despite dyslipidemia, only 6 patients were taking statins during the treatment with nilotinib and only 5 started it after 3 months of nilotinib: 3 patients were treated with rosuvastatin and 2 with pravastatin. Conclusions. Our findings suggest that a proper control of dyslipidemia, keeping cholesterol and triglycerides plasma levels ≤ 200 mg/dL and LDL ≤70 mg/dL is associated with reduced risk of AOEs in CML patients treated with nilotinib. An under estimation of the clinical importance of elevated plasma lipids as a risk factor for AOEs events represents a possible issue in the real-life. Figure 1 Disclosures Abruzzese: Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bms: Honoraria; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees. Galimberti:Incyte: Honoraria; Novartis: Speakers Bureau. Castagnetti:Novartis: Consultancy, Honoraria; Incyte: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Bristol Myers Squibb: Consultancy, Honoraria. Pregno:Incyte-Italy,: Membership on an entity's Board of Directors or advisory committees, Other: conference reports; Novartis-Italy: Membership on an entity's Board of Directors or advisory committees, Other: conference reports; Pfizer-Italy: Membership on an entity's Board of Directors or advisory committees, Other: conference reports. Bocchia:CELGENE: Honoraria; Incyte: Honoraria. Gugliotta:Novartis: Honoraria; Incyte: Honoraria; Pfizer: Honoraria. Foà:Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees; Incyte: Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2020
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  • 3
    In: Blood, American Society of Hematology, Vol. 134, No. Supplement_1 ( 2019-11-13), p. 1649-1649
    Abstract: 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.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2019
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  • 4
    In: Blood, American Society of Hematology, Vol. 108, No. 11 ( 2006-11-16), p. 2667-2667
    Abstract: Up to 40% of patients with myelodysplastic syndromes (MDS) respond to pharmacological doses of epoetin. Darbepoetin alfa (DPO) has a longer half-life and greater biological activity. Recent data suggest a 60% response rate in patients receiving DPO. We report preliminary results of a Phase II study in 41 patients with low and intermediate-1 risk MDS and Hb 〈 11 g/dL. The primary endpoint is to evaluate the efficacy of DPO for the treatment of anemia of MDS. Secondary endpoints are the evaluation of the safety of DPO and of the variations in Hb, the number of monthly transfusions and quality of life (QoL) in treated patients. Patients receive DPO 150 mcg s.c weekly to be doubled in non-responders. Treatment target is Hb =12.0 g/dL. Treatment is to be temporarily interrupted for Hb 〉 12 g/dL and re-initiated when Hb 〈 11.0 g/dL at the same dose administered every 3 weeks. Flow cytometry on bone marrow is performed at baseline and after 24 weeks. Single staining with CD34 PE and Annexin V FITC is followed by double staining (FITC/PE) to observe the CD34+/Annexin V+ events. QoL changes are measured using the QOL-E questionnaire. Results: The 33 patients who received at least 8 weeks of DPO included 19M/14F of median age 74 (range 49–84) years. Morphology was: 31 RA, 1 RARS and 1 CMML. IPSS score was low in 75%, and Int-1 in 25%. Serum epoetin levels were 〈 200 mU/ml. Meduab Hb level at baseline was 9.5 (range 7.0–10.8) g/dL. Six patients had previously received epoetin alfa or beta without success. Thirteen patients (39%) were transfusion-dependent. At the initial dosage, 6 transfusion-free patients (30%) responded at 4 weeks (3 reached the endpoint of Hb=12.0 g/dL). Total number of cases responding at 8 weeks were 17, including 7 (53%) transfusion-dependent patients. Ten responses were minor (30%) and 7 major (21%). After dosage doubling, there were 56% responders of the 16 patients that have completed the study at 24 weeks: 7 of 12 transfusion-free patients (2 at a dosage of 150 mcg/wk, 2 at 300 mcg/wk and 3 at 300 mcg every 3 weeks) and 2 of 4 transfusion-dependent patients at a dosage of 300 mcg/wk. Five patients reached Hb 〉 12g/dl during the study period. Finally, 3 of the 6 patients previously unresponsive to epoetin responded to DPO. At univariate ANOVA analysis, response to treatment was associated with increases in QOL-E treatment outcome index (p=0.033), specific (p=0.009), fatigue (p= 0.013), physical (p=0.001), functional (p=0.042), social (0.001), general (p=0.001), and total (p=0.004) scores. There were significant reductions in CD34+ cells (p=0.025) and apoptotic cells (p=0.008) and these were associated with treatment response (p=0.045 and p=0.065, respectively). No adverse events were reported. Conclusions: DPO is safe and well-tolerated in patients with MDS. A reduction in apoptotic cells is observed during treatment. Therapeutic response is associated with improvements in QoL. Our study suggests that DPO is effective for the treatment of anemia of MDS.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2006
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  • 5
    In: Blood, American Society of Hematology, Vol. 132, No. Supplement 1 ( 2018-11-29), p. 3021-3021
    Abstract: Introduction: Bosutinib is a Src/Abl tyrosine kinase inhibitor (TKI) currently licensed for patients with Ph+ chronic-phase (CP), accelerated-phase (AP), or blast-phase (BP) Chronic Myeloid Leukemia after failure or intolerance to at least 2 other TKIs. It can also be prescribed, in accordance with label if, after failure of the first TKI therapy, another option does not seem feasible. Previous studies demonstrated a potent activity of second-line bosutinib across a spectrum of BCR-ABL1 mutations and a distinct toxicity profile compared to other TKIs. Aim: We retrospectively assessed the efficacy and safety of real life Bosutinib administration in 85 patients resistant/refractory or intolerant to other TKIs, referred to 22 Italian Hematological Institutions. The main features at Bosutinib start are reported in the Table. Results: At Bosutinib start, all patients were in CP. 60 patients (71%) were resistant/refractory, 25 (29%) were intolerant to previous TKIs. BCR-ABL1 kinase mutations were reported in 5/35 evaluable patients (14%); no T315I was reported. The number of previous TKIs was less than 3 in 24/85 patients (28%) and 3 or more in 61 (72%). Comorbidities were present in 63 patients (74%), the most common being arterial hypertension (40), diabetes (14), cardiac disease (10) and chronic obstructive pulmonary disease (6). The most frequent concomitant medications were: antihypertensive in 55% patients, antiplatelets in 26%, antidiabetic in 19%. The initial dose was 100 mg in 4/85 patients (5%), 200 mg in 24 (28%), 300 mg in 18 (22%), 400 in 8 (9%); 31 patients (36%) started at the full standard dose of 500 mg. Major Molecular Response (MMR)/Deep Molecular Response (DMR) were achieved by 37/80 (46%) evaluable patients; 43/80 patients (54%) never reached a MMR/DMR at any time. Best responses in these cases were: Complete Hematologic Response (CHR) in 4 patients (9%), Partial Cytogenetic Response (PCyR) in 6 (14%), Complete Cytogenetic Response (CCyR) in 10 (23%). Dose reductions were necessary in 4 patients (5%) due to adverse events (2 cases of diarrhea, 1 transaminase elevation, 1 skin rash). After a median follow-up of 26 months (range 3-49), 75/85 patients (88%) are alive and 54/75 patients (72%) are still in treatment. Discontinuations were due to: intolerance in 8/75 patients (11%), loss of response in 3/75 (4%), resistance to therapy in 10/75 (13%). Hematological toxicity was observed in 14 patients (16%), any grade, and grade 3-4 in 3 (3%). Extra-hematological toxicity was reported in 41/85 patients (48%), any grade, and grade 3-4 in 14 patients (16%). Causes of death were: acute myocardial infarction (3), cardiac failure (2), acute respiratory distress (2), allogeneic transplant complications (1), cerebral hemorrhage (2). Conclusions: In our "real life experience" with Bosutinib, we confirm a stable long-term efficacy in heavily pre-treated, mainly elderly patients with intolerance/resistance to other TKIs, who show an initial response to treatment, as reported in clinical trials. Patients show a fast response to the drug (mainly at three months). Hematological and extrahematological toxicities are manageable. Disclosures Breccia: BMS: Honoraria; Incyte: Honoraria; Pfizer: Honoraria; Novartis: Honoraria. Abruzzese:Novartis: Consultancy; Ariad: Consultancy; BMS: Consultancy; Pfizer: Consultancy. Castagnetti:Bristol Meyers Squibb: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Incyte: Consultancy, Honoraria; Novartis: Consultancy, Honoraria. Bonifacio:Novartis: Research Funding; Amgen: Consultancy; Pfizer: Consultancy; Incyte: Consultancy; Bristol Myers Squibb: Consultancy.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2018
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  • 6
    In: Hematological Oncology, Wiley, Vol. 38, No. 4 ( 2020-10), p. 607-610
    Type of Medium: Online Resource
    ISSN: 0278-0232 , 1099-1069
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2020
    detail.hit.zdb_id: 2001443-0
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  • 7
    In: British Journal of Haematology, Wiley, Vol. 125, No. 3 ( 2004-05), p. 330-336
    Type of Medium: Online Resource
    ISSN: 0007-1048
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    Language: English
    Publisher: Wiley
    Publication Date: 2004
    detail.hit.zdb_id: 1475751-5
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  • 8
    In: American Journal of Hematology, Wiley, Vol. 95, No. 10 ( 2020-10)
    Type of Medium: Online Resource
    ISSN: 0361-8609 , 1096-8652
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2020
    detail.hit.zdb_id: 1492749-4
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  • 9
    In: Annals of Hematology, Springer Science and Business Media LLC, Vol. 99, No. 7 ( 2020-07), p. 1525-1530
    Type of Medium: Online Resource
    ISSN: 0939-5555 , 1432-0584
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
    detail.hit.zdb_id: 1458429-3
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  • 10
    In: International Journal of Cardiology, Elsevier BV, Vol. 301 ( 2020-02), p. 163-166
    Type of Medium: Online Resource
    ISSN: 0167-5273
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2020
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