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  • 1
    In: Blood, American Society of Hematology, Vol. 140, No. Supplement 1 ( 2022-11-15), p. 947-949
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2022
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 2
    In: Leukemia Research, Elsevier BV, Vol. 39, No. 10 ( 2015-10), p. 1028-1033
    Type of Medium: Online Resource
    ISSN: 0145-2126
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2015
    detail.hit.zdb_id: 2008028-1
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  • 3
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 34, No. 25 ( 2016-09-01), p. 2988-2996
    Abstract: This international phase III, randomized, placebo-controlled, double-blind study assessed the efficacy and safety of lenalidomide in RBC transfusion–dependent patients with International Prognostic Scoring System lower-risk non-del(5q) myelodysplastic syndromes ineligible for or refractory to erythropoiesis-stimulating agents. Patients and Methods In total, 239 patients were randomly assigned (2:1) to treatment with lenalidomide (n = 160) or placebo (n = 79) once per day (on 28-day cycles). The primary end point was the rate of RBC transfusion independence (TI) ≥ 8 weeks. Secondary end points were RBC-TI ≥ 24 weeks, duration of RBC-TI, erythroid response, health-related quality of life (HRQoL), and safety. Results RBC-TI ≥ 8 weeks was achieved in 26.9% and 2.5% of patients in the lenalidomide and placebo groups, respectively (P 〈 .001). Ninety percent of patients achieving RBC-TI responded within 16 weeks of treatment. Median duration of RBC-TI with lenalidomide was 30.9 weeks (95% CI, 20.7 to 59.1). Transfusion reduction of ≥ 4 units packed RBCs, on the basis of a 112-day assessment, was 21.8% in the lenalidomide group and 0% in the placebo group. Higher response rates were observed in patients with lower baseline endogenous erythropoietin ≤ 500 mU/mL (34.0% v 15.5% for 〉 500 mU/mL). At week 12, mean changes in HRQoL scores from baseline did not differ significantly between treatment groups, which suggests that lenalidomide did not adversely affect HRQoL. Achievement of RBC-TI ≥ 8 weeks was associated with significant improvements in HRQoL (P 〈 .01). The most common treatment-emergent adverse events were neutropenia and thrombocytopenia. Conclusion Lenalidomide yields sustained RBC-TI in 26.9% of RBC transfusion–dependent patients with lower-risk non-del(5q) myelodysplastic syndromes ineligible for or refractory to erythropoiesis-stimulating agents. Response to lenalidomide was associated with improved HRQoL. Treatment-emergent adverse event data were consistent with the known safety profile of lenalidomide.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2016
    detail.hit.zdb_id: 2005181-5
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  • 4
    In: Blood, American Society of Hematology, Vol. 124, No. 21 ( 2014-12-06), p. 409-409
    Abstract: Background: Treatment options for RBC-TD pts with lower-risk MDS without del(5q) who are unresponsive or refractory to ESAs are very limited. In a previous phase 2 study, MDS-002 (CC-5013-MDS-002), LEN was associated with achievement of RBC-transfusion independence (TI) ≥ 56 days in 26% of pts with IPSS Low/Int-1-risk MDS without del(5q) (Raza et al. Blood 2008;111:86-93). This international phase 3 study (CC-5013-MDS-005) compared the efficacy and safety of LEN versus PBO in RBC-TD pts with IPSS Low/Int-1-risk MDS without del(5q) unresponsive or refractory to ESAs. Methods: This multicenter, randomized, double-blind, parallel-group phase 3 study included RBC-TD pts (≥ 2 units packed RBCs [pRBCs]/28 days in the 112 days immediately prior to randomization) with IPSS Low/Int-1-risk MDS without del(5q), who were unresponsive or refractory to ESAs (RBC-TD despite ESA treatment with adequate dose and duration, or serum erythropoietin [EPO] 〉 500 mU/mL). Pts were randomized 2:1 to oral LEN 10 mg once daily (5 mg for pts with creatinine clearance 40–60 mL/min) or PBO. Pts with RBC-TI ≥ 56 days or erythroid response by Day 168 continued double-blind treatment until erythroid relapse, disease progression, unacceptable toxicity, or consent withdrawal. The primary endpoint was RBC-TI ≥ 56 days (defined as absence of any RBC transfusions during any 56 consecutive days). Secondary endpoints included time to RBC-TI, duration of RBC-TI, RBC-TI ≥ 168 days, progression to acute myeloid leukemia (AML; WHO criteria), overall survival (OS), and safety. Baseline bone marrow gene expression profiles were evaluated according to the Ebert signature (PloS Med 2008;5:e35) identified as predictive of LEN response. Clinical trial identifier: CT01029262. Results: The intent-to-treat population comprises 239 pts (LEN, n = 160; PBO, n = 79). Baseline characteristics were comparable across treatment groups; median age 71 years (range 43–87), 67.8% male, and median time from diagnosis 2.6 years (range 0.1–29.6). Pts received a median of 3.0 pRBC units/28 days (range 1.5–9.8) and 83.7% received prior therapy, including ESAs (78.7%). Significantly more LEN pts achieved RBC-TI ≥ 56 days versus PBO (26.9% vs 2.5%; P 〈 0.001; Table). The majority (90%) of pts with RBC-TI ≥ 56 days responded within 16 weeks of treatment. Median duration of RBC-TI ≥ 56 days was 8.2 months (range 5.2–17.8). Baseline factors significantly associated with achievement of RBC-TI ≥ 56 days with LEN were: prior ESAs (vs no ESAs; P = 0.005), serum EPO ≤ 500 mU/mL (vs 〉 500 mU/mL; P = 0.015), 〈 4 pRBC units/28 days (vs ≥ 4 pRBC units/28 days; P = 0.036), and female sex (vs male; P = 0.035). RBC-TI ≥ 168 days was achieved in 17.5% and 0% of pts in the LEN and PBO groups, respectively. The incidence of AML progression (per 100 person-years) was 1.91 (95% CI 0.80–4.59) and 2.46 (95% CI 0.79–7.64) for LEN and PBO pts, respectively, with median follow-up 1.6 and 1.3 years. Death on treatment occurred in 2.5% of pts on either LEN or PBO. The follow-up period was insufficient to permit OS comparison between the 2 groups. Myelosuppression was the main adverse event (AE); in the LEN versus PBO groups, respectively, grade 3–4 neutropenia occurred in 61.9% versus 11.4% of pts, and grade 3–4 thrombocytopenia in 35.6% versus 3.8% of pts. Discontinuations due to AEs were reported in 31.9% LEN and 11.4% PBO pts; among the 51 LEN pts who discontinued due to AEs, 14 discontinuations were due to thrombocytopenia and 8 due to neutropenia. In the subset of pts evaluated for the Ebert signature (n = 203), the predictive power of the signature was not confirmed. Conclusions: LEN therapy was associated with a significant achievement of RBC-TI ≥ 56 days in 26.9% of pts with a median duration of RBC-TI of 8.2 months; 90% of pts responded within 16 weeks of treatment. These data were consistent with response rates seen in the MDS-002 trial. The overall safety profile was consistent with the known safety profile of LEN and these data suggest LEN can be safely and effectively used in this patient population. Figure 1 Figure 1. Disclosures Santini: Celgene Corporation: Honoraria; Janssen: Honoraria; Novartis: Honoraria; Glaxo Smith Kline: Honoraria. Off Label Use: Trial of Lenalidomide in non-del5q MDS. Almeida:Celgene Corporation: Consultancy, Speakers Bureau. Giagounidis:Celgene Corporation: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Vey:Celgene: Honoraria. Mufti:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Buckstein:Celgene: Research Funding. Mittelman:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Platzbecker:Celgene: Research Funding. Shpilberg:Celgene Corporation: Consultancy, Honoraria. del Canizo:Celgene Corporation: Consultancy, Research Funding. Gattermann:Celgene: Honoraria, Research Funding; Novartis: Honoraria, Research Funding. Ozawa:Celgene: Consultancy, not specified Other. Zhong:Celgene: Employment, Equity Ownership. Séguy:Celgene: Employment, Equity Ownership. Hoenekopp:Celgene: Employment, Equity Ownership. Beach:Celgene: Employment, Equity Ownership. Fenaux:Novartis: Research Funding; Janssen: Research Funding; Celgene: Research Funding.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2014
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 5
    In: Blood, American Society of Hematology, Vol. 112, No. 11 ( 2008-11-16), p. 3238-3238
    Abstract: Background: Nilotinib is a potent and highly selective BCR-ABL kinase inhibitor approved for the treatment of Philadelphia chromosome-positive chronic myeloid leukemia patients in chronic (CML-CP) or accelerated phase (CML-AP) who are resistant or intolerant to prior therapy including imatinib. Methods: This open-label, single-arm, phase 2 study was designed to evaluate the efficacy and safety of nilotinib in CML-CP patients resistant or intolerant to imatinib. Imatinib intolerant patients with prior major cytogenetic response (MCyR) on imatinib were not eligible for this trial. Nilotinib was dosed at 400 mg twice daily with the option of dose escalation to 600 mg twice daily if responses were inadequate. Rate of MCyR was the primary endpoint. Secondary endpoints included complete cytogenetic response (CCyR), complete hematological response (CHR), duration of MCyR, survival, and safety. Results: A total of 321 CML-CP patients (71% imatinib-resistant; 29% imatinib-intolerant) were evaluated. Most patients were heavily pretreated with 72% having received more than 600 mg/day of imatinib prior to study entry. Furthermore, imatinib-intolerant patients could not have achieved prior MCyR on imatinib therapy. Median duration of prior imatinib treatment was 33 months (range 0.3–95 months). Dose reductions (25%) and discontinuations (15%) due to adverse events were infrequent on nilotinib therapy and median dose intensity (788 mg/day; range 151–1112 mg/day) closely approximated the planned dose. Median duration of exposure was 465 days (15.5 months). Overall, nilotinib therapy resulted in rapid and durable hematologic and cytogenetic responses. Of all imatinib-resistant and –intolerant patients, 58% achieved MCyR (1 month median time to MCyR), with 72% of patients having a baseline CHR achieving MCyR. The MCyR rate was 63% in imatinibintolerant and 56% in imatinib-resistant patients, respectively. Overall, 42% of patients achieved a CCyR (50% in imatinib-intolerant and 39% in imatinib-resistant patients, respectively). Responses were durable, with 84% of patients maintaining their MCyR at 18 months. Estimated overall survival (OS) rates at 12 and 18 months were 95% and 91%, respectively. Nearly half of all patients (47%) were still receiving nilotinib at the time of cut-off for data analysis. Longer follow-up has not significantly changed the safety profile of nilotinib. The most frequently reported grade 3/4 biochemical laboratory abnormalities were elevated lipase (16%), hypophosphatemia (15%), hyperglycemia (12%), and elevated total bilirubin (7%). Overall, biochemical laboratory abnormalities were transient and clinically asymptomatic. Grade 3/4 non-hematologic adverse events were infrequent with rash, headache, and diarrhea occurring in only 2% of patients. No pleural or pericardial effusions were documented during nilotinib therapy. The most common grade 3/4 hematological laboratory abnormalities included neutropenia (30%), thrombocytopenia (28%), and anemia (10%). Overall, QTcF changes greater than 60 milliseconds from baseline were infrequent, occurring in only 8 patients (2.5%), and QTcF prolongation 〉 500 milliseconds was uncommon ( 〈 1%), occurring in only 3 patients. Brief dose interruptions were sufficient to manage most adverse events. Conclusions: Nilotinib is highly effective and produces rapid and durable responses in CML-CP patients who failed prior therapy including imatinib due to resistance or intolerance and is an important treatment option for this patient population. Nilotinib is well tolerated with minimal occurrence of grade 3/4 adverse events; safety profile has not changed with longer follow-up.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2008
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 6
    In: Blood, American Society of Hematology, Vol. 118, No. 21 ( 2011-11-18), p. 510-510
    Abstract: Abstract 510 Background: MDS is a disease of predominantly elderly patients with a median age of 〉 70 years. At present there is a lack of data on MDS patient management in Germany. The following analysis offers a comprehensive insight into diagnosis, prognosis and management of MDS in German clinical practice. First results in 2009 showed that age was a key decision driver for MDS management, particularly with regards to cytogenetic testing, IPSS evaluation and choices of active treatment. The aim of a 2010 update was to monitor changes in management of MDS patients, especially in patients 〉 75 years of age. Methods: The patient sample was defined based on a structural analysis taking into account the distribution of treatment prevalence by institutional type as well as the regional population density. 886 centers involved in MDS management including university hospitals (UH), community hospitals (CH) and office-based hematologists (OBH) were contacted. 94 centers provided information on their respective patient numbers during the third quarter of 2010, with 1,611 patients corresponding to 12% of the estimated national prevalence. The distribution of patients by institution was 10% UH, 55% CH, and 35% OBH. In order to adequately represent UH and to avoid bias due to a too small sample size, the proportion of patients treated in UH was adjusted to 33% in our sample. The adjusted sample consisted of 46 centres (12 UH, 15 CH and 19 OBH) which documented 365 patients. Patient samples in 2010 and 2009 were comparable. Consistent with 2009, patients with a treatment decision (diagnosis, start, change or termination of therapy) in the third-fourth quarter were included in this analysis. Results: Compared to 2009, cytogenetic testing at first diagnosis substantially increased from 67% to 86% in 2010. The biggest change was observed in patients 〉 75 years with an absolute increase of 31%, reaching 75% in 2010 (fig. 1). Despite this change, a significant difference still remains in the level of cytogenetic testing between patients '75 and 〉 75 years (92% vs. 75%, p 〈 0,0001) and a higher use in UH compared to OBH (96% vs. 84%, p 〈 0,0001). Overall, prognostic IPSS assessment at first diagnosis increased from 61% in 2009 to 71% in 2010, but only from 51% to 53% in patients 〉 75 years. With 26%, WPSS use tripled in 2010 compared to 2009, whereby WPSS was almost always (in 99% of cases) used as an adjunct to and not as a substitute for IPSS. In 2010, 22% of all MDS patients did not receive any therapy. Of those treated, 52% received supportive care only, 45% received active treatment (i.e. chemo-, immunomodulatory or epigenetic therapy), 2% SCT, and 1% other treatments. Overall, compared to 2009, the proportion of active treatment remained stable. In the IPSS high risk group, the proportion of active treatment went up from 64% to 96%, declined from 34% to 20% in low risk MDS, but remained stable in patients unclassified by IPSS. In 43% of these patients cytogenetic testing was performed. A significantly lower use of active treatment was still observed in patients 〉 75 years (27% vs. 56%, p 〈 0,0001, fig. 2). As in 2009, the most frequently and increasingly used active drug in 2010 was azacitidine. When trying to identify factors driving active treatment, bivariate analysis showed a significant positive correlation with age ≤75 years, hospital as center type, and Karnofsky-index ≤80% (p 〈 0,01). Multivariate analysis revealed age ≤75 years as the most important factor (p 〈 0,001), followed by Karnofsky-index ≤80% (p=0,044). Discussion: There seemed to be an increasing awareness and utilization of both cytogenetic testing and IPSS assessment in 2010 vs. 2009. This translated into more frequent use of IPSS for clinical decision making, with a positive correlation between higher IPSS scores and start of active treatment, providing a potential benefit to high risk MDS patients. In patients 〉 75 years, however, IPSS usage remained unchanged despite the increase in cytogenetic testing. It appears that treatment decisions for these patients are more strongly influenced by age and cytogenetics than by IPSS assessment. This leaves room for improvement since under-utilization of prognostic assessment may lead to undertreatment of older MDS patients. Disclosures: Gattermann: Celgene: Consultancy, Research Funding. Kuendgen:Celgene: Honoraria. Kellermann:Celgene: Consultancy, Research Funding. Zeffel:Celgene: Employment. Paessens:Celgene: Employment. Germing:Celgene: Consultancy, Research Funding.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2011
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 7
    Online Resource
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    American Society of Hematology ; 2012
    In:  Blood Vol. 120, No. 16 ( 2012-10-18), p. 3167-3168
    In: Blood, American Society of Hematology, Vol. 120, No. 16 ( 2012-10-18), p. 3167-3168
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2012
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 8
    In: Blood, American Society of Hematology, Vol. 104, No. 11 ( 2004-11-16), p. 1434-1434
    Abstract: VPA affects the growth and differentiation of malignant cells in vitro. Tumour cell differentiation induced by VPA appears to be coupled with the drug’s capability to inhibit histone deacetylation. Since myelodysplastic syndromes are characterized by impaired maturation, differentiation induction is an attractive approach. 26 patients (11 RCMD, 1 PSA, 3 RSCMD, 2 RAEB I, 7 RAEB II, 2 CMML) were started on VPA monotherapy (serum concentration 50–100mg/ml), with addition of ATRA (80mg/m2/d in two divided doses, every other week) planned for patients who did not respond or who relapsed. To enhance responses, 3 patients (2 RCMD, 1 RAEB I) were treated with VPA+ATRA from the start. Median treatment duration was 6 months (2–30) for VPA and 3 months (1–26) for ATRA. Hematological improvement, according to international working group criteria (Cheson, et al., 2000), was observed in 8 patients (31%) on VPA monotherapy: 2 major and 1 minor platelet, 3 major and 1 minor erythroid, and 2 major neutrophil responses, as well as 1 PR. 1 patient with RAEB II had a peripheral blast clearance and a reduction of bone marrow blasts. Another patient showed an increase in platelets from 33.000/ml to 138.000/ml. This response was not sufficient to fulfil IWG criteria because of a duration of only 36 days. 1 patient with CMML had a normalization of elevated blood counts and a slight reduction in spleen size. Skin infiltration with monocytic cells vanished after treatment with VPA. 5 out of 7 patients relapsed after a median of 4 months (2–14), four of these were switched to VPA+ATRA, with 2 responding for another 11 and 21 months, respectively. 10 patients showed stable, 11 progressive disease. Of the non-responding patients, 11 were changed to VPA+ATRA, without success. Responders had the WHO subtype of RCMD in 4 cases and RSCMD, PSA and RAEBII in 1 case each. Regarding prognostic groups, 3 of 4 patients belonging to the IPSS low-risk category showed a major response. In contrast, none of 2 high-risk patients had a response. There was no difference in the distribution of normal and aberrant karyotypes in both groups, but responders had only single aberrations (including -Y in 3 patients), while all 3 patients with complex aberrations did not respond to VPA treatment. Response to VPA was not associated with age, gender, bone marrow blast count or dosage of VPA. 3 out of 4 patients receiving concomitant erythropoietin treatment for 3, 7 and 18 month prior to VPA, respectively, responded to the study medication. A synergism, perhaps by inhibition of apoptosis, appears possible. Side effects were mild. A decrease in platelet count 〉 50% occurred in 8 patients and appeared to be attributable to study medication in 2. Intermittent ATRA treatment was well tolerated. Grade 1–2 skin toxicity was observed in 9 patients. Response to VPA monotherapy was better than response to first-line combination with ATRA. Nevertheless, we observed a prolonged response to the combination in some patients. We conclude that valproic acid shows encouraging signs of clinical activity in MDS with a low toxicity profile. However, we have the impression that VPA monotherapy is not sufficiently active to achieve prolonged benefits. It rather looks like a promising candidate for combination regimens like cytokines, demethylating agents or FTIs. ATRA may be effective when added later.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2004
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 9
    In: Blood, American Society of Hematology, Vol. 126, No. 23 ( 2015-12-03), p. 3167-3167
    Abstract: Background and Rationale: Allogeneic stem cell transplantation (allo-SCT) has a curative potential in patients (pts) with MDS. While non-relapse mortality (NRM) has been continuously reduced during the years, relapse incidence remained almost unchanged. As a consequence relapse remains the major cause of treatment failure and is associated with a poor prognosis. Although a better knowledge about relapse biology and kinetics could eventually help to optimize post-transplant maintenance or salvage therapies and to define intervals for minimal residual disease (MRD) monitoring, so far only a few studies exclusively focused on relapse patterns in MDS. Material and Methods: To address this in detail, we retrospectively analyzed data of 140 pts (median age: 58 y, 23-72) with MDS (n=125) or secondary AML (sAML, n=15), who had received a first allo-SCT from a related (29%) or unrelated (71%) donor at our center between 2001 and 2014. Fifty pts (36%) relapsed after allo-SCT and were therefore included in this study focusing on relapse characteristics, treatment strategies and outcome. In pts with sequential cytogenetic analyses available we also compared karyotypes pre-transplant and at relapse in order to track clonal evolution. Results: Overall, hematological relapse was diagnosed in 46 pts (92%), while 4 pts (8%) had a molecular relapse. Median time to relapse was 248 days (range: 53-3349) with the great majority of relapses occurring within the first 3 years (1st year: 62%; 2nd year: 84%; 3rd year: 94%). Only 3 pts (6%) relapsed beyond the 3rd year. To identify predictors for early relapse we compared those pts (defined by an interval between transplant and relapse 〈 248 days) with those pts who relapsed late ( 〉 248 days). Hereby, we identified a longer interval between diagnosis and transplant (p=0.0122) and the use of intensive chemotherapy prior transplant (p=0.0209) as predictors for early relapse. Pre-transplant blast count (p=0.07), disease progression prior transplant (p=0.08) and presence of poor/very poor risk cytogenetics according to IPSS-R (p=0.08) also tended to predict early relapse. Sequential cytogenetic analyses revealed that 18 of 30 pts (60%) carried a karyotype at relapse with at least 1 of the abnormalities present before allo-SCT suggesting a common clonal origin. In 12 (40%) of these pts cytogenetic results before allo-SCT and at relapse were identical, while in 6 pts (20%) additional aberrations were detected. In the remaining 12 pts (40%) we observed new cytogenetic aberrations (n=7) or even evolution of a complex karyotype (n=5) indicating clonal evolution or the emergence of a previously undetectable clone. Following relapse, the majority of pts (n=36) received at least one salvage therapy, while 9 pts received BSC only (missing n=5). Salvage therapies consisted of hypomethylating agents (n=32, 31 Aza, 1 DAC) +/- DLI, intensive chemotherapy (n=1), DLI only (n=1) and 2nd allo-SCT (n=2). In contrast to previous studies, time between allo-SCT and relapse here predicted response to hypomethylating agents as indicated by a significantly higher CR rate in pts with late relapse (CR rates: all pts: 37,5%; late relapse 62,5% vs. early relapse 12,5%, p=0.0091). With a median follow-up of 43 months, 14 pts (28%) are currently alive and in remission. Median overall survival (OS) of the entire group was 273 d (range:3-2717) and 2-year OS rate 33%. Median survival and 2-year OS rate were significantly higher in pts with late relapse compared to those with early relapse (1435 vs.169 d; 55% vs.10%; p=0.0036). Conclusion: Relapses mostly occur within the first 3 years after allo-SCT arguing in favor for stringent MRD monitoring and post-transplant interventions during this interval. Pts with a longer time to transplant or need for induction therapy are at risk for early relapse, and the interval from allo-SCT until relapse represents a crucial factor to predict response to salvage therapy and survival. Cytogenetic patterns at relapse suggest that MDS relapses can arise from original clones but also frequently due to emergence of new clones. Disclosures Gattermann: Novartis: Honoraria, Research Funding.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2015
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 10
    In: Blood, American Society of Hematology, Vol. 110, No. 11 ( 2007-11-16), p. 735-735
    Abstract: Background: Nilotinib is a novel, selective BCR-ABL inhibitor, designed to bind the ATP-binding site of BCR-ABL protein with higher affinity than imatinib. It is more potent than imatinib (IC50 〈 30 nM) against wild-type BCR-ABL and active against 32/33 imatinib-resistant BCR-ABL mutants. Methods: This open-label study was designed to evaluate the safety and efficacy of nilotinib in patients (pts) with Philadelphia (Ph+) imatinib-resistant or -intolerant CML-CP. Planned nilotinib dose was 400 mg twice daily (BID) with escalation to 600 mg BID for inadequate responses. The primary endpoint was the rate of major cytogenetic response (MCyR) determined on the conventional intent-to-treat patient population. Cytogenetic response (CyR) was assessed by bone marrow karyotyping; peripheral blood FISH was used if a marrow sample cannot be obtained. Results: This analysis includes data from 320 pts who received at least 6 months of nilotinib therapy (70.6% imatinib-resistant; 29.4% imatinib-intolerant). The median age was 58 years, the median duration of CML was 57.3 months, and 50.3% were males. Treatment with nilotinib is ongoing in 188 pts (58.8%) and 132 pts (41.3%) discontinued the treatment [51 (15.9%) for disease progression, 51 (15.9%) for adverse events (AE)]. The median duration of nilotinib exposure was 341 (1–624) days and the median average dose intensity was 792.1 mg/d (47.9–1111.6 mg/d). The dose was escalated to 600 mg BID in only 51 pts (15.9%). Complete hematological remission (CHR) at baseline was reported in 114 pts. Of the remaining 206 pts, 157 (76.2%) achieved CHR in 1 month. MCyR was observed in 180 pts (56.3%): 128/320 pts (40.0%) had complete cytogenetic response (CCyR). The median time to CHR and to first MCyR was 1.0 and 2.8 months, respectively. The median duration of MCyR has not been reached. Minor and Minimal CyR was seen in 22 (6.9%) and 42 (13.1%) patients respectively. The most frequent Grade 3/4 hematologic laboratory abnormalities included thrombocytopenia (27%), neutropenia (30%), anemia (9%), and asymptomatic serum lipase elevation (15%). Conclusion: The present study confirms nilotinib is an effective therapeutic option in CML-CP pts with imatinib-resistance or -intolerance, with an acceptable safety and tolerability profile. With longer follow up, cytogenetic response continues to increase and no change in safety profile has been observed on nilotinib therapy.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2007
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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