The Efficacy and Safety of Darbepoetin Alfa for Treating Anemia in Low-Risk Myelodysplastic Syndrome Patients: Results after 53/55 Weeks.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2671-2671
Author(s):  
Janice Gabrilove ◽  
Ronald Paquette ◽  
Roger M. Lyons ◽  
Chaudhry Mushtaq ◽  
Mikkael A. Sekeres ◽  
...  
Keyword(s):  
Darbepoetin Alfa ◽  
Low Risk ◽  
Open Label ◽  
Eligibility Criteria ◽  
Erythroid Response ◽  
Kaplan Meier ◽  
Risk Of Progression ◽  
Red Blood Cell Transfusions ◽  
Hematopoietic Disorders ◽  
A Minor

Abstract Myelodysplastic syndromes (MDS) are hematopoietic disorders characterized by peripheral cytopenias and risk of progression to leukemia. MDS patients (pts) are often anemic, resulting in increased red blood cell transfusions (tfns) and fatigue. Previous studies have shown that 150mcg/week (wk) or 300mcg/wk of the erythropoiesis-stimulating agent (ESA) darbepoetin alfa (DA) can raise hemoglobin (Hb) levels in low-risk MDS pts (Patton et al. J Support Oncol.2005;3:419–426). We present data from a phase 2, single-arm, open-label study on the efficacy of 500mcg DA administered every three wks (Q3W) for treating anemia in low-risk MDS pts. Eligibility criteria included ≥18 years, anemia (Hb ≤11g/dL), and low- or intermediate-1-risk MDS (IPSS definition). If pts did not respond by wk 7, the dosing frequency was escalated to Q2W. After the last DA dose on wk 52, the end of study (EOS) was wk 53 (Q2W dosing) or wk 55 (Q3W dosing). The primary endpoint was the percentage of pts with an erythroid response (International Working Group criteria) by wk 13. Secondary 53/55-wk endpoints included incidence of erythroid responses, incidence of tfns, and the change in Hb levels and FACT-F score from baseline (BL). Results were stratified by whether pts had prior ESA therapy: ESA-naive (ESA-N) vs prior ESA-treated (ESA-T). A previous interim analysis showed that low-risk MDS pts could achieve an erythroid response after 13 wks of DA 500mcg Q3W (Gabrilove et al. Blood.2005;106:abstract2541). This is the first reported summary after 53/55 wks (n=148). Of 98 ESA-N pts, 47% were men, 85% were white, and the mean (SD) age was 74 (10) years; the 50 ESA-T pts had similar demographics. Both ESA-N and ESA-T pts had similar BL Hb (Table). By wk 53/55, the percentage (95% CL) of pts with a major erythroid response (≥2g/dL Hb rise from BL or tfn independence) was 56% (46, 66) in ESA-N pts and 30% (17, 43) in ESA-T pts. Both ESA-N and ESA-T pts had a clinically meaningful rise (≥3 points) in FACT-F score from BL. Of the 148 pts, 89% reported adverse events (AEs) with the most common AE being fatigue, 7% had AEs considered related to DA treatment, and 1.4% had thromboembolic events. These results suggested that DA 500mcg Q3W was well tolerated and increased Hb levels in the MDS pts in this study. ESA-N, N=98 ESA-T, N=50 KM%= Kaplan-Meier percentage Crude % (95% CL) pts with a major erythroid response 56% (46, 66) 30% (17, 43) Crude % (95% CL) pts with a minor erythroid response 15% (8, 22) 20% (9, 31) Mean (SD) BL Hb, g/dL 9.8 (1.0) [n=84] 10.0 (1.2) [n=41] Mean (SD) Hb change (BL to wk 53/55) (last value carried forward) 1.1 (1.6) [n=84] 0.2 (1.7) [n=41] Crude % (95% CL) pts achieved target Hb (11g/dL) 68% (58, 78) [n=87] 46% (31, 60) [n=46] Mean (SD) Hb after reached Hb target, g/dL 11.7 (0.8) [n=68] 11.6 (0.9) [n=25] KM% (95% CL) pts with tfns (wk 1 to EOS) 29% (19, 39) 43% (27, 59) KM% (95% CL) pts with tfns (wk 5 to EOS) 28% (19, 38) [n=96] 43% (26, 60) [n=45] Mean (SD) change in FACT-F score (BL to wk 53/55) 5.8 (8.6) [n=45] 7.2 (9.3) [n=15]

A Phase 2, Single-Arm, Open-Label Trial To Evaluate the Effectiveness of Darbepoetin alfa for the Treatment of Anemia in Patients with Low-Risk Myelodysplastic Syndrome.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2541-2541
Author(s):  
Janice Gabrilove ◽  
Ron Paquette ◽  
Roger Lyons ◽  
Chaudhry Mushtaq ◽  
Mikkael Sekeres ◽  
...  
Keyword(s):  
Adverse Event ◽  
Primary Endpoint ◽  
Darbepoetin Alfa ◽  
Test Period ◽  
Low Risk ◽  
Refractory Anemia ◽  
Phase 2 ◽  
Open Label ◽  
Erythroid Response ◽  
Open Label Trial

Abstract Patients (pts) with myelodysplastic syndromes (MDS) often develop clinically significant anemia due to ineffective hematopoiesis. Using the erythropoiesis-stimulating protein (ESP) epoetin alfa to treat anemia results in an average response rate of approximately 30% (40% when used with G-CSF) in low-risk MDS pts. Darbepoetin alfa (DA) (150 to 300 mcg/week) also effectively increases hemoglobin (Hb) concentrations and reduces red blood cell transfusion requirements in these pts. This study is a phase 2, single-arm, open-label trial (with a planned sample size of 200 pts), evaluating the efficacy of DA 500 mcg given SC every 3 weeks (Q3W) for treating anemia in low-risk MDS pts during the 13-week (wk) test period. Eligible pts had low or intermediate-1 risk MDS (IPSS/FAB criteria), anemia (Hb ≤11 g/dL), and no previous or ongoing chemotherapy or biologic response modifiers (except for ESPs [stopped ≥7 days and ≤1 month before enrollment] and G-CSF [allowed for infection before enrollment]). The primary endpoint is the proportion of pts achieving an erythroid response during the test period. Secondary endpoints include the change in Hb from baseline at wk 13, transfusion incidence, and impact on pt-reported fatigue. This study has completed enrollment and data are available from a planned interim analysis of the first 100 pts; 63 pts were not treated with an ESP before enrollment (ESP-naive ([EN]). Of the EN pts, 51% were female, 81% were white, 73% had low-risk MDS, 22% had intermediate-1 risk MDS, 60% had refractory anemia (RA), 30% had RA with ringed sideroblasts (RARS), and 10% had RA with excess blasts (RAEB). Results for EN pts are shown in the table. Of the 37 pts treated with an ESP before enrollment, the crude percentage (95% CL) with an overall (major plus minor) erythroid response was 36% (20, 53), the crude percentage (95% CL) with a major erythroid response was 21% (7, 35), and the crude percentage (95% CL) that required transfusions during wks 1 to 13 was 32% (17, 48 ). During the test period, 16% of all pts reported a serious adverse event (none were considered treatment-related). Injection site pain (reported by 4% of pts) was the most common treatment-related adverse event. No thromboembolic events have been reported. Interim results from this fully-enrolled study indicate that DA 500 mcg Q3W appears to be well tolerated and capable of increasing Hb levels in low-risk MDS pts. Final results for the primary endpoint will be presented. ESP-Naive Pts, N = 63 No. of Patients Evaluated (n) Crude % (95% CL) pts with overall erythroid response 77% (66, 88) 57 Crude % (95% CL) pts with major erythroid response 47% (34, 60) 57 Mean (95% CL) baseline Hb 9.9 (9.6, 10.1) g/dL 56 Mean (95% CL) change in Hb at wk 13 (last value carried forward approach) 1.1 (0.8, 1.4) g/dL 56 Crude % (95% CL) pts with transfusions (wks 1 to 13) 17% (8, 27) 63 Mean (95% CL) baseline FACT-F score 29.8 (25.9, 33.8) 46 Mean (95% CL) change in FACT-F score at wk 13 (available data) 5.7 (2.3, 9.0) 41

Darbepoetin alfa Maintains Hemoglobin Levels in Patients with Myelodysplastic Syndromes (MDS) after Therapeutic Interchange from Epoetin alfa: Results of a Retrospective Chart Review.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4708-4708 ◽  
Author(s):  
Jeffrey Patton ◽  
Yong Mun ◽  
Joel Wallace
Keyword(s):  
Darbepoetin Alfa ◽  
Chart Review ◽  
Retrospective Chart Review ◽  
Epoetin Alfa ◽  
Minor Response ◽  
Therapeutic Substitution ◽  
Kaplan Meier ◽  
Major Response ◽  
A Minor ◽  
The Impact

Abstract Patients with MDS often receive erythropoietic therapy for the treatment of anemia resulting from the disease. This retrospective chart review examined the impact of switching patients from their current dosing regimens of epoetin alfa (Procrit®) to darbepoetin alfa (Aranesp®) 200 mcg every two weeks (Q2W) following the implementation of therapeutic substitution guidelines in September 2003. Key eligibility criteria included: ≥ 18 years old with a diagnosis of MDS, and treatment with epoetin alfa therapy between May 2003 and January 2004. Patients receiving epoetin alfa therapy were either switched to darbepoetin alfa, or allowed to remain on epoetin alfa, depending on whether their treating physician had adopted therapeutic substitution guidelines. To ensure full characterization of the patient population, in the 16 weeks prior to the time of the therapeutic substitution, detailed demographic and disease characteristics were collected, in addition to dose requirements, transfusion status and hemoglobin profiles. To assess the impact on clinical outcomes, data were collected for 16 weeks after the therapeutic substitution guidelines were implemented (defined as the treatment period). Patients identified in the chart review who received at least one dose of study drug during both time periods were included in the analysis. Response was defined according to the international working group on MDS definitions (Cheson et al., Blood, 2000; 96(12):3671–4). Kaplan-Meier estimates (95% CL) for the percentage of patients with a major response (hemoglobin [Hb] change ≥ 2 g/dL over baseline or transfusion independence) or a minor response (Hb increase ≥ 1 g/dL to < 2 g/dL or a 50% reduction in transfusion requirements) during the treatment period were calculated. Data were abstracted from 142 patient charts, 112 (62 darbepoetin alfa; 50 epoetin alfa) of whom had confirmatory evidence of MDS available in their records (a documented bone marrow biopsy, French-American-British [FAB] classification, or karyotype [confirmed MDS population]). Baseline demographics for the confirmed MDS population were similar between the two cohorts. For those patients with data available, the majority had a FAB classification of refractory anemia with ≤ 5% bone marrow blasts. Mean baseline Hb was 11.0 g/dL for the darbepoetin alfa cohort (n=61) and 11.3 g/dL for the epoetin alfa cohort (n=48). The Kaplan-Meier percentage (95% CL) of patients with a major response was 27% (15, 39) for the darbepoetin alfa cohort and 19% (7, 30) for the epoetin alfa cohort; a minor response was noted for 46% (33, 59) and 47% (31, 63) of patients in the darbepoetin alfa and epoetin alfa cohorts, respectively. The Kaplan-Meier (95% CL) proportion of patients receiving red blood cell transfusions was similar between the groups: 8% (1, 15) for the darbepoetin alfa cohort and 12% (3, 22) for the epoetin alfa cohort. This study indicates that darbepoetin alfa achieved comparable clinical outcomes with epoetin alfa for the treatment of anemia in patients with confirmed MDS.

Darbepoetin alfa for treating anemia in low-risk myelodysplastic syndrome patients: Interim results after 27/28 weeks

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 6564-6564 ◽  
Author(s):  
R. Paquette ◽  
J. Gabrilove ◽  
R. Lyons ◽  
C. Mushtaq ◽  
M. Sekeres ◽  
...  
Keyword(s):  
Myelodysplastic Syndrome ◽  
Darbepoetin Alfa ◽  
Response Rate ◽  
Low Risk ◽  
Epoetin Alfa ◽  
Average Response Rate ◽  
Pilot Studies ◽  
Erythroid Response ◽  
Clinically Significant ◽  
Esa Therapy

6564 Background: Patients (pts) with myelodysplastic syndrome (MDS) disorders often develop anemia, resulting in increased transfusions and fatigue. Using the erythropoiesis-stimulating agent (ESA) epoetin alfa to treat anemia in low-risk MDS pts results in an average response rate of 30% (40% when used with G-CSF). Pilot studies suggest that 150 or 300 mcg/week (wk) darbepoetin alfa (DA) can raise hemoglobin (Hb) levels in anemic MDS pts. Methods: This fully enrolled (n = 209), phase 2, single-arm, 52-wk ongoing study is examining DA 500 mcg every 3 weeks (Q3W) for treating anemic pts (Hb ≤ 11 g/dL) with low- or intermediate-risk MDS (IPSS definition). The study’s primary endpoint is the proportion of pts achieving an erythroid response by 13 wks. Other endpoints include the proportion of pts achieving an erythroid response by 27/28 wks and change in both Hb levels and FACT-F scores. Results are stratified by whether pts received ESA therapy before enrollment: ESA-naïve (ESA-N) vs ESA-treated (ESA-T). Results: Previous interim data suggested that low-risk MDS pts can achieve a major erythroid response after 13 wks of DA 500 mcg Q3W. This is the first reported summary of results from a planned interim analysis after 27/28 wks of treatment (n = 129). Of 84 ESA-N pts, 51% were men, 86% were white, and the average (SD) age was 74.1 (9.7) years; the 45 ESA-T pts had similar demographics. During 27/28 wks of treatment, a majority of pts achieved a major erythroid response. ESA-N pts had a mean (SD) 1.2 (1.4) g/dL rise in Hb levels from BL and a clinically significant increase in FACT-F score from BL ( Table ). Of the 129 pts analyzed after 27/28 wks, 83% reported an adverse event (AE) and none reported serious treatment-related AEs or thrombotic events (of 189 pts analyzed after 13 wks, 1 pt reported a serious treatment-related AE). Conclusions: These interim results suggest that DA 500 mcg Q3W is well tolerated and can raise Hb levels in anemic, low-risk MDS pts. Final 27/28-wk data from all enrolled pts (n = 209) will be shown. [Table: see text] [Table: see text]

Effectiveness of darbepoetin alfa 300 mcg every 3 weeks in patients with chemotherapy-induced anemia

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 18545-18545
Author(s):  
E. Hernandez ◽  
J. Dibenedetto ◽  
D. Kotasek ◽  
P. Ganly ◽  
P. Silberstein ◽  
...  
Keyword(s):  
Darbepoetin Alfa ◽  
Neutralizing Antibodies ◽  
Treatment Phase ◽  
Double Blind Study ◽  
Tumor Type ◽  
Open Label ◽  
Eligibility Criteria ◽  
Double Blind ◽  
Point Change ◽  
Combined Analysis

18545 Background: Patients (pts) receiving chemotherapy (CTX) often experience anemia resulting in decreased quality of life. We performed a post hoc combined analysis of 2 clinical studies of darbepoetin alfa (DA) 300 mcg every 3 weeks (Q3W), allowing for comparison of larger treatment groups. Methods: Eligibility criteria of the 2 studies were similar: pts ≥ 18 yrs old with nonmyeloid malignancy, anemia (hemoglobin [Hb] < 11 g/dL), and receiving CTX. Study 1 (20030232) was a phase 3, randomized, placebo-controlled, double-blind, study involving 16 wks of treatment with end of treatment phase (EOTP) visit at wk 19. Study 2 (20030206) was a single-arm, open-label, phase 4 study involving 13-wks of treatment with EOTP visit at wk 16. Efficacy endpoints included: percentage of pts achieving target Hb (≥ 11 g/dL without RBC transfusion [TFN] within 28 days), pts requiring TFNs between wk 1 and EOTP, pts requiring TFNs between wk 5 and EOTP, pts with a ≥ 3-point change in FACT-F score, and pts achieving ≥ 1-g/dL increase in Hb after 4 wks of therapy. Results: In both studies, 61% of pts were women and 79% were white. The mean (SD) age was 64.5 years (12.1) for Study 1 and 62.6 years (13.3) for Study 2. The most common tumor type was breast (26% in Study 1; 29% in Study 2). Mean (SD) baseline (BL) Hb values were 10.1 (0.9) and 10.1 (0.7) g/dL for Study 1 and Study 2 respectively, and mean (SD) baseline FACT-F scores were 27.3 (12.8) and 27.9 (12.3) respectively. See Table for endpoints. Combined analysis showed that increasing Hb by ≥ 1 g/dL after 4 wks of therapy was a poor predictor of clinical outcomes (avoidance of TFN, sensitivity = 56.2%; achievement of Hb target, sensitivity = 57.8%). Safety outcomes were similar and expected for this population. DA appeared to be well-tolerated. No pts exhibited neutralizing antibodies to DA. Conclusions: This combined analysis provides further evidence of the effectiveness of DA Q3W dosing in this pt population. This dosing interval may facilitate the administration of DA in synchronization with Q3W CTX regimens. [Table: see text] [Table: see text]

Baseline predictors of response to treatment with darbepoetin-alpha (DA) in anemic patients with low-risk myelodysplastic syndrome (MDS)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7081-7081
Author(s):  
J. Gabrilove ◽  
R. Paquette ◽  
R. Lyons ◽  
C. Mushtaq ◽  
M. Sekeres ◽  
...  
Keyword(s):  
Low Risk ◽  
Response To Treatment ◽  
Refractory Anemia ◽  
Open Label ◽  
Disease Category ◽  
Serious Adverse Events ◽  
Endogenous Erythropoietin ◽  
Erythroid Response ◽  
Predictors Of Response ◽  
Duration Of Response

7081 Background: Patients (pts) with MDS often develop anemia, resulting in fatigue and an increased requirement for transfusions. The erythropoiesis-stimulating agent (ESA) DA can raise hemoglobin (Hb) levels in low-risk MDS pts. Previous analyses suggest that baseline (BL) endogenous erythropoietin (eEPO) levels and French-American-British (FAB) disease category are predictors of response to ESAs. Methods: This was a phase 2, open-label, 52-week (wk) study of DA administered 500 mcg every 3 wks (Q3W) to anemic (Hb=11g/dL), low- or intermediate-risk MDS pts. Pts received 500 mcg DA Q2W if they did not respond by wk 7. The last DA dose was at wk 52; end of study was wk 53 or 55 for pts receiving DA Q2W or Q3W, respectively. The primary endpoint was % pts with an erythroid response (International Working Group criteria) by wk 13. Other endpoints included change from BL in Hb and FACT-F score. Exploratory analyses examined the incidence of erythroid responses adjusted by FAB category (refractory anemia [RA], RA with ringed sideroblasts [RARS], or RA with excess blasts [RAEB]). Results: Final 53/55 wk data will be presented. Results were stratified by whether pts received an ESA before enrollment (ESA-naive [ESA-N] vs ESA-treated [ESA-T]). ESA-T pts are a heterogeneous group and their data are difficult to interpret; thus, predictors of response will be presented for ESA-N pts only. Of 144 ESA-N pts, 56% had RA, 37% had RARS, and 7% had RAEB. Most ESA-N pts achieved the target Hb and had a major erythroid response ( Table ). Pts with RA were more likely to achieve a major erythroid response than pts with RARS or RAEB. For ESA-T pts, demographics and type/length of ESA treatment will be presented. Of all pts, serious adverse events (SAEs) were reported in 62 (30%) pts and treatment-related SAEs in 2 (1%) pts. Conclusions: FAB category may affect response to DA in MDS pts. Additional data will be presented on the effect of BL eEPO, transfusion needs, and previous ESA treatment on response and duration of response. [Table: see text]

Darbepoetin alfa for treating anemia in patients with low-risk myelodysplastic syndromes: Exploratory analysis of baseline predictors of response

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 6579-6579 ◽  
Author(s):  
J. Gabrilove ◽  
R. Paquette ◽  
R. Lyons ◽  
C. Mushtaq ◽  
M. Sekeres ◽  
...  
Keyword(s):  
Myelodysplastic Syndromes ◽  
Darbepoetin Alfa ◽  
Significant Rise ◽  
Low Risk ◽  
Refractory Anemia ◽  
Endogenous Erythropoietin ◽  
Erythroid Response ◽  
Predictors Of Response ◽  
Response Table ◽  
Clinically Significant

6579 Background: Patients (pts) with myelodysplastic syndromes (MDS) often develop anemia, resulting in fatigue and increased transfusions. The erythropoiesis-stimulating agents (ESAs) epoetin alfa and darbepoetin alfa (DA) can raise hemoglobin (Hb) levels in low-risk MDS pts. Baseline (BL) endogenous erythropoietin (eEPO) levels, transfusion history, and FAB sub-type can be predictive factors of response to ESAs (Hellström-Lindberg et al., 2003). Methods: This is an ongoing, fully enrolled (n = 209), phase 2, single-arm, 52-week (wk) study of DA 500 mcg every three weeks (Q3W) for treating anemia (Hb ≤ 11 g/dL) in low- or intermediate-risk MDS pts. A planned interim analysis was done after 13 wks (n = 189). The primary endpoint is the proportion of pts with an erythroid response by 13 wks. Other endpoints include change in Hb levels and in FACT-F score from BL. Results are stratified by whether pts received an ESA before enrollment: ESA-naïve (ESA-N) pts vs ESA-treated (ESA-T) pts. Exploratory analyses of the percentage of pts with an erythroid response adjusted by BL eEPO or FAB category were done. Results: Of 130 ESA-N pts, 52% were women, 86% were white, 58% had refractory anemia (RA), 34% had RA with ringed sideroblasts (RARS), 8% had RA with excess blasts (RAEB), and the mean (SD) age was 74.8 (10.1) years. The 59 ESA-T pts had similar demographics. A majority of ESA-N pts had an erythroid response, achieved a target Hb of 11 g/dL, and had a clinically significant rise in FACT-F score; ESA-N pts with lower BL eEPO levels were more likely to have a major erythroid response ( Table ). A major erythroid response was seen in 50% of pts with RA (n = 111), in 30% of pts with RARS (n = 64), and in 23% of pts with RAEB (n = 13). Of all 189 pts, 78% had an adverse event (AE), 1 had a serious treatment-related AE (hypertension), and none had thrombotic events. Conclusions: These interim results suggest that FAB sub-type and BL eEPO may affect response. Final 13-wk data from all enrolled pts (n = 209) will be shown. [Table: see text] [Table: see text]

scholarly journals Myelodysplastic Syndromes with Isolated 20q Deletion: A New Clinical-Biological Entity?

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5516-5516
Author(s):  
Daniela De Benedittis ◽  
Luana Fianchi ◽  
Pasquale Niscola ◽  
Annalina Piccioni ◽  
Ambra Di Veroli ◽  
...  
Keyword(s):  
High Risk ◽  
Myelodysplastic Syndromes ◽  
Good Prognosis ◽  
Low Risk ◽  
Biological Entity ◽  
Entire Cohort ◽  
Prognostic Features ◽  
Erythroid Response ◽  
Risk Of Progression

Abstract Deletion of the chromosome 20 long arm (del20q) has been reported in 3-7% of patients with Myelodysplastic Syndromes (MDS). In particular, isolated del20q seems to be associated with good prognosis, low risk of progression to AML and prolonged survival: however, very few reports addressed this subset of MDS patients up to now. To highlight this issue, we collected data from all patients with MDS and isolated del20q diagnosed and followed by Centers of the Gruppo Romano-Laziale Sindromi Mielodisplastiche (GROM-L). On the whole, 53 patients were analysed: the main features at diagnosis of these patients are reported in the Table. Platelet (PLT) count was < 100 x 109/l in 28 patients (52.8%), Hb level was < 10.0 g/dl in 23 patients (43.3%) and neutrophil count was < 1.0 x 109/l in 12 patients (22.6%). As to risk prognostication, according to IPSS score 51 patients (96.2%) had low/intermediate-1 risk and 2 (3.8%) had intermediate-2/high risk: according to r-IPSS, 8 patients (15.1%) had very low risk, 20 (37.7%) low risk, 19 (35.9%) intermediate risk and 6 (11.3%) high risk. During follow-up, 14 patients (26.4%) did not need any therapy and were only observed, 36 (67.9%) were treated with Erythropoietin (EPO), 1 (1.9%) with hypomethylating agents, 2 (3.8%) with other treatments (TNF-α inhibitor, interferon). Among the 36 patients treated with ESA after a median interval from diagnosis of 5.0 months [interquartile range (IR) 1.2 - 27.6], 24 (66.6%) received α-EPO, 11 (30.5%) β-EPO and 1 (2.9%) darbopoietin. Two patients were too early (< 3 months of treatment) for response evaluation: among the 34 evaluable patients, 21 (61.7%) achieved stable erythroid response according IWG criteria (Hb increase > 1.5 g/dl in 18 patients and reduction > 50% of basal transfusion requirement in 3 patients) while 13 (38.2%) were resistant to EPO. Nine patients (17%) progressed to Acute Myeloid Leukemia (AML) after a median time from diagnosis of 16.8 months (IR 4.1 - 51.7). At the last follow-up, 21 patients (39.6%) died (13 from MDS/AML related causes and 8 from unrelated causes), 12 (22.6%) were lost to follow-up and 20(37.8%) were alive. Median Overall Survival (OS) of the entire cohort was 61.6 months (95%CI 42.2 - 81.0): the 10-year cumulative OS was 38.6% (95%CI 18.6 - 58.6) (Figure 1). In conclusion, as MDS represent a heterogeneous group of pathologies, many efforts are ongoing to identify patients with similar biological, clinical and prognostic features (eg 5q- syndrome, MDS with ring sideroblasts). From the scarce data in the literature and from our results, it is reasonable that also patients with isolated del20q may represent a distinct clinical and biological entity, with specific clinical and prognostic features (low PLT count, low number of marrow blasts, low IPSS and r-IPSS risk score, good response to EPO, long OS). The mechanisms underlying del20q are still unclear and warrant future molecular analysis. Disclosures Breccia: Novartis: Honoraria; BMS: Honoraria; Pfizer: Honoraria; Incyte: Honoraria.

scholarly journals New risk model is able to identify patients with a low risk of progression in systemic sclerosis

RMD Open ◽  
2021 ◽  
Vol 7 (2) ◽  
pp. e001524
Author(s):  
Nina Marijn van Leeuwen ◽  
Marc Maurits ◽  
Sophie Liem ◽  
Jacopo Ciaffi ◽  
Nina Ajmone Marsan ◽  
...  
Keyword(s):  
Machine Learning ◽  
Systemic Sclerosis ◽  
High Risk ◽  
Disease Progression ◽  
Risk Model ◽  
Immunosuppressive Drugs ◽  
Low Risk ◽  
Expert Assessment ◽  
Risk Of Progression

ObjectivesTo develop a prediction model to guide annual assessment of systemic sclerosis (SSc) patients tailored in accordance to disease activity.MethodsA machine learning approach was used to develop a model that can identify patients without disease progression. SSc patients included in the prospective Leiden SSc cohort and fulfilling the ACR/EULAR 2013 criteria were included. Disease progression was defined as progression in ≥1 organ system, and/or start of immunosuppression or death. Using elastic-net-regularisation, and including 90 independent clinical variables (100% complete), we trained the model on 75% and validated it on 25% of the patients, optimising on negative predictive value (NPV) to minimise the likelihood of missing progression. Probability cutoffs were identified for low and high risk for disease progression by expert assessment.ResultsOf the 492 SSc patients (follow-up range: 2–10 years), disease progression during follow-up was observed in 52% (median time 4.9 years). Performance of the model in the test set showed an AUC-ROC of 0.66. Probability score cutoffs were defined: low risk for disease progression (<0.197, NPV:1.0; 29% of patients), intermediate risk (0.197–0.223, NPV:0.82; 27%) and high risk (>0.223, NPV:0.78; 44%). The relevant variables for the model were: previous use of cyclophosphamide or corticosteroids, start with immunosuppressive drugs, previous gastrointestinal progression, previous cardiovascular event, pulmonary arterial hypertension, modified Rodnan Skin Score, creatine kinase and diffusing capacity for carbon monoxide.ConclusionOur machine-learning-assisted model for progression enabled us to classify 29% of SSc patients as ‘low risk’. In this group, annual assessment programmes could be less extensive than indicated by international guidelines.

scholarly journals A Novel Epigenetic Machine Learning Model to Define Risk of Progression for Hepatocellular Carcinoma Patients

2021 ◽  
Vol 22 (3) ◽  
pp. 1075
Author(s):  
Luca Bedon ◽  
Michele Dal Bo ◽  
Monica Mossenta ◽  
Davide Busato ◽  
Giuseppe Toffoli ◽  
...  
Keyword(s):  
Machine Learning ◽  
Hepatocellular Carcinoma ◽  
High Risk ◽  
Progression Free Survival ◽  
Low Risk ◽  
Functional Enrichment ◽  
Free Survival ◽  
High Risk Patients ◽  
Risk Of Progression ◽  
Risk Patients

Although extensive advancements have been made in treatment against hepatocellular carcinoma (HCC), the prognosis of HCC patients remains unsatisfied. It is now clearly established that extensive epigenetic changes act as a driver in human tumors. This study exploits HCC epigenetic deregulation to define a novel prognostic model for monitoring the progression of HCC. We analyzed the genome-wide DNA methylation profile of 374 primary tumor specimens using the Illumina 450 K array data from The Cancer Genome Atlas. We initially used a novel combination of Machine Learning algorithms (Recursive Features Selection, Boruta) to capture early tumor progression features. The subsets of probes obtained were used to train and validate Random Forest models to predict a Progression Free Survival greater or less than 6 months. The model based on 34 epigenetic probes showed the best performance, scoring 0.80 accuracy and 0.51 Matthews Correlation Coefficient on testset. Then, we generated and validated a progression signature based on 4 methylation probes capable of stratifying HCC patients at high and low risk of progression. Survival analysis showed that high risk patients are characterized by a poorer progression free survival compared to low risk patients. Moreover, decision curve analysis confirmed the strength of this predictive tool over conventional clinical parameters. Functional enrichment analysis highlighted that high risk patients differentiated themselves by the upregulation of proliferative pathways. Ultimately, we propose the oncogenic MCM2 gene as a methylation-driven gene of which the representative epigenetic markers could serve both as predictive and prognostic markers. Briefly, our work provides several potential HCC progression epigenetic biomarkers as well as a new signature that may enhance patients surveillance and advances in personalized treatment.

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