15 research outputs found
A phase 3 randomized, placebo-controlled study assessing the efficacy and safety of epoetin-α in anemic patients with low-risk MDS
No full textErythropoiesis-stimulating agents are first choice for treating anemia in low-risk MDS. This double-blind, placebo-controlled study assessed the efficacy and safety of epoetin-α in IPSS low- or intermediate-1 risk (i.e., low-risk) MDS patients with Hb ≤ 10.0 g/dL, with no or moderate RBC transfusion dependence (≤4 RBC units/8 weeks). Patients were randomized, 2:1, to receive epoetin-α 450 IU/kg/week or placebo for 24 weeks, followed by treatment extension in responders. The primary endpoint was erythroid response (ER) through Week 24. Dose adjustments were driven by weekly Hb-levels and included increases, and dose reductions/discontinuation if Hb > 12 g/dL. An independent Response Review Committee (RRC) blindly reviewed all responses, applying IWG-2006 criteria but also considering dose adjustments, drug interruptions and longer periods of observation. A total of 130 patients were randomized (85 to epoetin-α and 45 to placebo). The ER by IWG-2006 criteria was 31.8% for epoetin-α vs 4.4% for placebo (p < 0.001); after RRC review, the ER was 45.9 vs 4.4% (p < 0.001), respectively. Epoetin-α reduced RBC transfusions and increased the time-to-first-transfusion compared with placebo. Thus, epoetin-α significantly improved anemia outcomes in low-risk MDS. IWG-2006 criteria for ER may require amendments to better apply to clinical studies
Nevus Blue as a Sporadic Finding in a Patient with a Blue Toe?
No full textBACKGROUND: Blue nevus is an interesting finding, which aetiology and risk of locoregional and distant metastasis have not yet been fully clarified. It may be inherited or acquired, with sporadic cases usually presented as solitary lesions. It is often localised in the area of the head and less often on the arms, legs or trunk. Blue nevi are formations with relatively low but still possible potential for switching to melanoma.CASE REPORT: The patient we described was hospitalised for pronounced cyanosis of the small toe of the right foot, accompanied by painful symptoms at rest and pain symptoms for a few weeks. Using inpatient paraclinical and instrumental tests, the patient was diagnosed with cholesterol microembolism. During the dermatological examination, blue nevus on the contralaterally localised limb was also diagnosed as a sporadic finding. According to the patient’s medical history, the finding had existed for many years, but in the last few months, the patient has observed growth and progression in the peripheral zone of the nevus without any additional clinical symptoms.CONCLUSION: Due to the risk of progression to melanoma, the lesion was removed by radical excision, and the defect was closed by tissue advancement flap
GX-G3, a long-acting G-CSF, compared with pegfilgrastim in reducing duration of severe neutropenia after chemotherapy for non-Hodgkin's lymphoma.
No full textAnnual Meeting of the American-Society-of-Clinical-Oncology (ASCO) -- MAY 31-JUN 04, 2019 -- Chicago, IL[No Abstract Available]Amer Soc Clin Onco
Nevus Blue as a Sporadic Finding in a Patient with a Blue Toe?
No full textBACKGROUND: Blue nevus is an interesting finding, which aetiology and risk of locoregional and distant metastasis have not yet been fully clarified. It may be inherited or acquired, with sporadic cases usually presented as solitary lesions. It is often localised in the area of the head and less often on the arms, legs or trunk. Blue nevi are formations with relatively low but still possible potential for switching to melanoma.CASE REPORT: The patient we described was hospitalised for pronounced cyanosis of the small toe of the right foot, accompanied by painful symptoms at rest and pain symptoms for a few weeks. Using inpatient paraclinical and instrumental tests, the patient was diagnosed with cholesterol microembolism. During the dermatological examination, blue nevus on the contralaterally localised limb was also diagnosed as a sporadic finding. According to the patient’s medical history, the finding had existed for many years, but in the last few months, the patient has observed growth and progression in the peripheral zone of the nevus without any additional clinical symptoms.CONCLUSION: Due to the risk of progression to melanoma, the lesion was removed by radical excision, and the defect was closed by tissue advancement flap.</jats:p
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Phase II study of pevonedistat (P) + azacitidine (A) versus A in patients (pts) with higher-risk myelodysplastic syndromes (MDS)/chronic myelomonocytic leukemia (CMML), or low-blast acute myelogenous leukemia (LB AML) (NCT02610777)
No full text7506 Background: P, the first and only small-molecule inhibitor of the NEDD8-activating enzyme, disrupts proteasomal degradation of select proteins and has shown promising clinical activity and good tolerability in combination with A in AML. Methods: 120 pts with higher-risk (Revised International Prognostic Scoring System risk > 3) MDS/CMML or LB AML naïve to hypomethylating agents were randomized 1:1 to receive P 20 mg/m2 intravenously (IV) on days (d) 1, 3, 5 + A 75 mg/m2 (IV/subcutaneously) on d 1–5, 8, 9 (n = 58), or A alone (n = 62), in 28-d cycles until unacceptable toxicity, relapse, transformation to AML, or progression. The primary endpoint was overall survival (OS), although the study was underpowered for OS. Results: Baseline characteristics were generally balanced between arms. Pts received a median of 13.0 vs 8.5 cycles of P+A vs A. Median OS in the intent-to-treat (ITT) population with P+A vs A (n = 120) was 21.8 vs 19.0 mos (hazard ratio [HR] 0.80; 95% CI 0.51–1.26; P = .334; median follow-up 21.4 vs 19.0 mos). Subanalyses showed median OS with P+A vs A in higher-risk MDS (n = 67) of 23.9 vs 19.1 mos (HR 0.70; 95% CI 0.39–1.27; P = .240) and in LB AML (n = 36) of 23.6 vs 16.0 mos; HR 0.49; 95% CI 0.22–1.11; P = .081). Event-free survival (EFS – time from randomization to death/transformation to AML) with P+A vs A trended longer in the ITT population (median 21.0 vs 16.6 mos; HR 0.65; 95% CI 0.41–1.02; P = .060) and was significantly longer in higher-risk MDS (median 20.2 vs 14.8 mos; HR 0.54; 95% CI 0.29–1.00; P = .045). In response-evaluable pts, overall response rate was 71% (n = 39/55; 46% complete remission [CR] + CR with incomplete blood count recovery [CRi], 5% partial response [PR], 20% hematologic improvement [HI]) with P+A vs 60% (n = 32/53; 38% CR+CRi, 8% PR, 15% HI) with A. In higher-risk MDS, CR rate was 52% vs 27% ( P = .050) with P+A vs A. Median A dose intensity was 97% vs 98% with P+A vs A. Rates of grade ≥3 adverse events were 90% vs 87% with P+A vs A; the most common were 31% vs 27% neutropenia, 26% vs 29% febrile neutropenia, 19% vs 27% anemia, and 19% vs 23% thrombocytopenia. On-study deaths occurred in 9% of P+A pts and 16% of A pts. Conclusions: P+A had a comparable safety profile to A alone, did not increase myelosuppression, and maintained A dose intensity. Although not statistically significant, P+A increased OS, EFS, and response rates vs A, particularly in pts with higher-risk MDS. Further evaluation of P+A vs A is ongoing in a randomized phase. Clinical trial information: NCT02610777
S199: A PHASE 3, OPEN-LABEL, RANDOMIZED STUDY EVALUATING THE EFFICACY AND SAFETY OF SINGLE AGENT BELANTAMAB MAFODOTIN VS POMALIDOMIDE PLUS DEXAMETHASONE IN RELAPSED/REFRACTORY MULTIPLE MYELOMA (DREAMM-3)
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MDS-344: Pevonedistat Plus Azacitidine vs Azacitidine Alone in Higher-Risk Myelodysplastic Syndromes (MDS): Efficacy and Safety Results from Study P-2001 (NCT02610777)
No full textPevonedistat, an investigational, first-in-class NEDD8-activating enzyme inhibitor, disrupts protein homeostasis, leading to cancer cell death. For patients with higher-risk MDS ineligible for transplant, real-world data reveal median overall survival (OS) is 11–15 months with treatment, yet no novel treatments have been approved in a decade.
Patients with higher-risk MDS/chronic myelomonocytic leukemia or low-blast acute myeloid leukemia (AML) naive to hypomethylating agents were randomized 1:1, receiving pevonedistat (20 mg/m2 intravenously [IV], days 1, 3, 5) + azacitidine (75 mg/m2 IV/subcutaneously, days 1–5, 8, 9) (n=58) or azacitidine alone (n=62) in 28-day cycles until unacceptable toxicity, relapse, AML transformation, or progression. The study was powered for event-free survival (EFS: time from randomization to death/AML transformation, whichever occurred first). This report focuses on higher-risk MDS, including their cytogenetic and genetic characterization.
In patients with higher-risk MDS (n=67/120), baseline characteristics were balanced between arms. EFS was longer with pevonedistat+azacitidine vs azacitidine (median 20.2 vs 14.8 months; HR 0.54; 95% CI 0.29–1.00; p=.045). For patients with high-risk MDS assessed using the Cleveland Clinic model formula (n=16/arm), median EFS was 20.2 vs 11.7 months (HR 0.39; 95% CI 0.17–0.90; p=.023); median OS was 24.2 vs 14.2 months (HR 0.45; 95% CI 0.19–1.05; p=.056) with pevonedistat+azacitidine vs azacitidine. Overall response rate (complete remission [CR]+partial remission [PR]+hematological improvement, n=59 response-evaluable patients) was 79% with pevonedistat+azacitidine vs 57% with azacitidine, with a CR rate of 52% vs 27% (p=.050); median duration of response (DOR, CR+PR) was 34.6 vs 13.1 months (p=.106). Median (range) time to transformation (pevonedistat+azacitidine [n=5] vs azacitidine [n=9]) was 12.2 (4.6–12.6) vs 5.9 (1.7–14.8) months. Median dose intensity of azacitidine was 98% in both arms. Exposure-adjusted adverse event (AE) rates, normalized by mean cycles dosed, were lower with pevonedistat+azacitidine vs azacitidine. Pevonedistat+azacitidine clinical activity was observed in patients with adverse-risk mutations.
In patients with higher-risk MDS, pevonedistat+azacitidine prolonged EFS, delayed AML transformation, nearly doubled CR rate, and tripled DOR vsazacitidine alone. EFS and OS favored pevonedistat+azacitidine vs azacitidine in patients with high-risk MDS. Exposure-adjusted AE rates were lower with pevonedistat+azacitidine vs azacitidine without added myelosuppression
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Poster: MDS-344: Pevonedistat Plus Azacitidine vs Azacitidine Alone in Higher-Risk Myelodysplastic Syndromes (MDS): Efficacy and Safety Results from Study P-2001 (NCT02610777)
No full textBritish Journal of Haematology / A phase III randomized, multicentre, double blind, active controlled trial to compare the efficacy and safety of two different anagrelide formulations in patients with essential thrombocythaemia the TEAMET 2·0 trial
No full textAnagrelide is an established treatment option for essential thrombocythaemia (ET ). A prolonged release formulation was developed with the aim of reducing dosing frequency and improving tolerability, without diminishing efficacy. This multicentre, randomized, double blind, activecontrolled, noninferiority trial investigated the efficacy, safety and tolerability of anagrelide prolonged release (APR ) over a reference product in highrisk ET patients, either anagrelidenaïve or experienced. In a 6 to 12week titration period the individual dose for the consecutive 4week maintenance period was identified. The primary endpoint was the mean platelet count during the maintenance period (3 consecutive measurements, day 0, 14, 28). Of 112 included patients 106 were randomized. The mean screening platelet counts were 822 10/l (95% confidence interval (CI ) 707936 10/l) and 797 10/l (95% CI 708883 10/l) for APR and the reference product, respectively. Both treatments effectively reduced platelet counts, to mean 281 10/l for APR (95% CI 254311) and 305 10/l (95% CI 276337) for the reference product (P < 0·0001, for noninferiority). Safety and tolerability were comparable between both drugs. The novel prolongedrelease formulation was equally effective and well tolerated compared to the reference product. APR provides a more convenient dosing schedule and will offer an alternative to licensed immediaterelease anagrelide formulations.(VLID)510150
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MDS-336: Phase 2 Study of Pevonedistat + Azacitidine versus Azacitidine in Patients with Higher-Risk Myelodysplastic Syndromes (MDS)/Chronic Myelomonocytic Leukemia (CMML) or Low-Blast Acute Myelogenous Leukemia (LB-AML) (NCT02610777): Subset Analysis in Higher-Risk MDS
No full textPevonedistat, the first small-molecule inhibitor of NEDD8-activating enzyme, disrupts proteasomal degradation of select proteins.
Patients with higher-risk MDS/CMML (IPSS-R >3, including intermediate [≥5% blasts], high, or very high risk) or LB-AML naïve to hypomethylating agents were randomized 1:1 to receive intravenous pevonedistat 20 mg/m2 on days 1, 3, and 5 plus intravenous/subcutaneous azacitidine 75 mg/m2 on days 1–5, 8, and 9 (n=58), or azacitidine alone (n=62), in 28-day cycles. This abstract focuses on the higher-risk MDS subgroup.
The study was powered on an endpoint of event-free survival (EFS). Overall survival (OS), overall response rate (ORR) and safety were also assessed. Patient-reported health-related quality of life (HRQoL) was evaluated using the European Organization for Research and Treatment of Cancer (EORTC) QoL Questionnaire-C30. Mutational profiling was performed on screening bone marrow aspirate samples.
In the intent-to-treat (ITT) population (n=120), EFS trended longer (median, 21.0 vs 16.6 months; hazard ratio [HR]=0.67; 95% CI, 0.42–1.05; P=.076) and median OS was 21.8 vs 19.0 months (HR=0.80; 95% CI, 0.51–1.26; P=.334) with pevonedistat+azacitidine vs azacitidine. In patients with higher-risk MDS (n=67), EFS was longer (median, 20.2 vs 14.8 months; HR=0.54; 95% CI, 0.29–1.00; P=0.045) and median OS was 23.9 vs 19.1 months (HR=0.70; 95% CI, 0.39–1.27; P=0.240) with pevonedistat+azacitidine vs azacitidine. In response-evaluable patients with higher-risk MDS (n=59), ORR was 79% (pevonedistat+azacitidine) vs 57% (azacitidine); median duration of response was 34.6 vs 13.1 months, respectively. Median azacitidine dose intensity was 98% (both arms) in patients with higher-risk MDS. With pevonedistat+azacitidine vs azacitidine, 94% vs 83% of patients with higher-risk MDS had grade ≥3 adverse events (most common: neutropenia [38% vs 37%], febrile neutropenia [22% vs 31%]). No difference was observed in patient-reported HRQoL between arms, with similar mean scores maintained from study entry to end of treatment. Clinical activity was observed with pevonedistat+azacitidine in patients with higher-risk MDS harboring poor prognostic mutations.
Pevonedistat+azacitidine led to longer EFS vs azacitidine in higher-risk MDS, had a comparable safety profile to azacitidine alone, and azacitidine dose intensity was maintained. A randomized phase 3 trial (NCT03268954) is ongoing
