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Phase 2, single-arm trial to evaluate the effectiveness of darbepoetin alfa for correcting anaemia in patients with myelodysplastic syndromes.

Gabrilove J, Paquette R, Lyons RM, Mushtaq C, Sekeres MA, Tomita D, Dreiling L - Br. J. Haematol. (2008)

Bottom Line: Secondary end-points included the incidence of erythroid responses at weeks 28 and 55, [or weeks 27 and 53 for dose escalations to every two weeks (Q2W)], and safety parameters.Thromboembolic or related adverse events occurred in 2% of patients; no pulmonary embolisms were reported.In conclusion, darbepoetin alfa, 500 microg Q3W appeared well tolerated and increased haemoglobin levels in low-risk MDS patients.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, Mt Sinai School of Medicine, New York, NY 10029, USA. janice.gabrilove@mssm.edu

ABSTRACT
Patients with myelodysplastic syndromes (MDS) often develop anaemia resulting in frequent transfusions and fatigue. Darbepoetin alfa is an erythropoiesis-stimulating agent (ESA) approved for treating chemotherapy-induced anaemia. This single-arm, phase 2 study examined the efficacy of darbepoetin alfa 500 microg every 3 weeks (Q3W) for treating anaemia in low-risk MDS patients (after 6 weeks, poor responders received darbepoetin alfa 500 microg every 2 weeks). The primary end-point was the incidence of erythroid responses (International Working Group criteria) after 13 weeks of therapy. Secondary end-points included the incidence of erythroid responses at weeks 28 and 55, [or weeks 27 and 53 for dose escalations to every two weeks (Q2W)], and safety parameters. Analyses were stratified by the patient's previous ESA therapy status [ESA-naïve (n = 144) vs. prior ESA-treated (n = 62)]. After 13 weeks of therapy, 49% of ESA-naïve patients and 26% of prior ESA-treated patients achieved a major erythroid response. After 53/55 weeks, 59% of ESA-naïve patients and 34% of prior ESA-treated patients achieved a major erythroid response; 82% of ESA-naïve patients and 55% of prior ESA-treated patients achieved target haemoglobin of 110 g/l. Thromboembolic or related adverse events occurred in 2% of patients; no pulmonary embolisms were reported. In conclusion, darbepoetin alfa, 500 microg Q3W appeared well tolerated and increased haemoglobin levels in low-risk MDS patients.

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Kaplan–Meier plots of the time to haemoglobin response and of the time to target haemoglobin over the 28-week treatment period. (A) The time to haemoglobin response for erythropoiesis-stimulating agent (ESA)-naïve patients and prior ESA-treated patients. (B) The time to target haemoglobin for ESA-naïve patients and prior ESA-treated patients. n below each graph represents the number of patients at risk for an event (patients were censored after an end-point was achieved).
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fig03: Kaplan–Meier plots of the time to haemoglobin response and of the time to target haemoglobin over the 28-week treatment period. (A) The time to haemoglobin response for erythropoiesis-stimulating agent (ESA)-naïve patients and prior ESA-treated patients. (B) The time to target haemoglobin for ESA-naïve patients and prior ESA-treated patients. n below each graph represents the number of patients at risk for an event (patients were censored after an end-point was achieved).

Mentions: A separate analysis looked at the percentage of patients achieving a haemoglobin response (haemoglobin increase of ≥20 g/l from baseline in the absence of RBC transfusions within the preceding 28 d) after 53/55 weeks of darbepoetin alfa therapy. Thirty-one patients were not eligible for the haemoglobin response analysis as they had received RBC transfusions within 28 d of the baseline haemoglobin assessment, and thus had baseline haemoglobin values that were affected by recent transfusion. The KM percentage (95% CL) of eligible patients who achieved a haemoglobin response was 68% (60, 75). In ESA-naïve patients (n = 126), the KM percentage (95% CL) achieving a haemoglobin response was 73% (64, 81) and in prior ESA-treated patients (n = 49) the percentage of responders was 53% (37, 70). Figure 3A shows the KM curve for the time to haemoglobin response in both ESA-naïve and prior ESA-treated patients during the 28-week treatment period. As the haemoglobin response accounted for all patients with a major erythroid response, this figure also demonstrates the time to major erythroid response during the treatment period. The KM median (95% CL) time to haemoglobin response over the extended treatment period was 11 weeks (9, 15) in ESA-naïve patients and 31 weeks (13, NE) in prior ESA-treated patients (the upper 95% CL in prior ESA-treated patients could not be estimated).


Phase 2, single-arm trial to evaluate the effectiveness of darbepoetin alfa for correcting anaemia in patients with myelodysplastic syndromes.

Gabrilove J, Paquette R, Lyons RM, Mushtaq C, Sekeres MA, Tomita D, Dreiling L - Br. J. Haematol. (2008)

Kaplan–Meier plots of the time to haemoglobin response and of the time to target haemoglobin over the 28-week treatment period. (A) The time to haemoglobin response for erythropoiesis-stimulating agent (ESA)-naïve patients and prior ESA-treated patients. (B) The time to target haemoglobin for ESA-naïve patients and prior ESA-treated patients. n below each graph represents the number of patients at risk for an event (patients were censored after an end-point was achieved).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2654479&req=5

fig03: Kaplan–Meier plots of the time to haemoglobin response and of the time to target haemoglobin over the 28-week treatment period. (A) The time to haemoglobin response for erythropoiesis-stimulating agent (ESA)-naïve patients and prior ESA-treated patients. (B) The time to target haemoglobin for ESA-naïve patients and prior ESA-treated patients. n below each graph represents the number of patients at risk for an event (patients were censored after an end-point was achieved).
Mentions: A separate analysis looked at the percentage of patients achieving a haemoglobin response (haemoglobin increase of ≥20 g/l from baseline in the absence of RBC transfusions within the preceding 28 d) after 53/55 weeks of darbepoetin alfa therapy. Thirty-one patients were not eligible for the haemoglobin response analysis as they had received RBC transfusions within 28 d of the baseline haemoglobin assessment, and thus had baseline haemoglobin values that were affected by recent transfusion. The KM percentage (95% CL) of eligible patients who achieved a haemoglobin response was 68% (60, 75). In ESA-naïve patients (n = 126), the KM percentage (95% CL) achieving a haemoglobin response was 73% (64, 81) and in prior ESA-treated patients (n = 49) the percentage of responders was 53% (37, 70). Figure 3A shows the KM curve for the time to haemoglobin response in both ESA-naïve and prior ESA-treated patients during the 28-week treatment period. As the haemoglobin response accounted for all patients with a major erythroid response, this figure also demonstrates the time to major erythroid response during the treatment period. The KM median (95% CL) time to haemoglobin response over the extended treatment period was 11 weeks (9, 15) in ESA-naïve patients and 31 weeks (13, NE) in prior ESA-treated patients (the upper 95% CL in prior ESA-treated patients could not be estimated).

Bottom Line: Secondary end-points included the incidence of erythroid responses at weeks 28 and 55, [or weeks 27 and 53 for dose escalations to every two weeks (Q2W)], and safety parameters.Thromboembolic or related adverse events occurred in 2% of patients; no pulmonary embolisms were reported.In conclusion, darbepoetin alfa, 500 microg Q3W appeared well tolerated and increased haemoglobin levels in low-risk MDS patients.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, Mt Sinai School of Medicine, New York, NY 10029, USA. janice.gabrilove@mssm.edu

ABSTRACT
Patients with myelodysplastic syndromes (MDS) often develop anaemia resulting in frequent transfusions and fatigue. Darbepoetin alfa is an erythropoiesis-stimulating agent (ESA) approved for treating chemotherapy-induced anaemia. This single-arm, phase 2 study examined the efficacy of darbepoetin alfa 500 microg every 3 weeks (Q3W) for treating anaemia in low-risk MDS patients (after 6 weeks, poor responders received darbepoetin alfa 500 microg every 2 weeks). The primary end-point was the incidence of erythroid responses (International Working Group criteria) after 13 weeks of therapy. Secondary end-points included the incidence of erythroid responses at weeks 28 and 55, [or weeks 27 and 53 for dose escalations to every two weeks (Q2W)], and safety parameters. Analyses were stratified by the patient's previous ESA therapy status [ESA-naïve (n = 144) vs. prior ESA-treated (n = 62)]. After 13 weeks of therapy, 49% of ESA-naïve patients and 26% of prior ESA-treated patients achieved a major erythroid response. After 53/55 weeks, 59% of ESA-naïve patients and 34% of prior ESA-treated patients achieved a major erythroid response; 82% of ESA-naïve patients and 55% of prior ESA-treated patients achieved target haemoglobin of 110 g/l. Thromboembolic or related adverse events occurred in 2% of patients; no pulmonary embolisms were reported. In conclusion, darbepoetin alfa, 500 microg Q3W appeared well tolerated and increased haemoglobin levels in low-risk MDS patients.

Show MeSH
Related in: MedlinePlus