40 research outputs found
achievement of red blood cell transfusion independence in red blood cell transfusion dependent patients with lower risk non del 5q myelodysplastic syndromes correlates with serum erythropoietin levels
AbstractIn the randomized, phase 3, MDS-005 study (NCT01029262), lenalidomide-induced red blood cell transfusion independence (RBC-TI) in 27% of transfusion-dependent patients with lower-risk non-d..
Oral azacitidine prolongs survival of patients with AML in remission independently of measurable residual disease status
Measurable residual disease (MRD) in patients with acute myeloid leukemia (AML) in remission after intensive chemotherapy is predictive of early relapse and poor survival. Postremission maintenance therapy that prolongs MRD negativity or converts MRD+ patients to MRD- status may delay or prevent relapse and improve overall survival (OS). In the phase 3 QUAZAR AML-001 trial, oral azacitidine (oral-AZA; formerly CC-486), a hypomethylating agent, significantly prolonged OS and relapse-free survival (RFS) compared with placebo in patients aged >= 55 years with AML in first remission after intensive chemotherapy who were not candidates for hematopoietic stem cell transplantation. In this trial, MRD (>= 0.1% leukemic cells in bone marrow) was assessed by multiparameter flow cytometry in serial samples collected at baseline and on day 1 of every 3 cycles. As expected, baseline MRD status was significantly associated with both OS and RFS. Multivariate analyses showed oral-AZA significantly improved OS and RFS vs placebo independent of baseline MRD status. Oral-AZA treatment also extended the duration of MRD negativity by 6 months vs placebo and resulted in a higher rate of conversion from MRD+ at baseline to MRD- during treatment: 37% vs 19%, respectively. In the oral-AZA arm, 24% of MRD responders achieved MRD negativity >6 months after treatment initiation. Although presence or absence of MRD was a strong prognostic indicator of OS and RFS, there were added survival benefits with oral-AZA maintenance therapy compared with placebo, independent of patients' MRD status at baseline.Peer reviewe
Management of adverse events in patients with acute myeloid leukemia in remission receiving oral azacitidine: experience from the phase 3 randomized QUAZAR AML-001 trial
Background
Most older patients with acute myeloid leukemia (AML) who attain morphologic remission with intensive chemotherapy (IC) will eventually relapse and post-relapse prognosis is dismal. In the pivotal QUAZAR AML-001 trial, oral azacitidine maintenance therapy significantly prolonged overall survival by 9.9 months (P < 0.001) and relapse-free survival by 5.3 months (P < 0.001) compared with placebo in patients with AML in first remission after IC who were not candidates for transplant. Currently, the QUAZAR AML-001 trial provides the most comprehensive safety information associated with oral azacitidine maintenance therapy. Reviewed here are common adverse events (AEs) during oral azacitidine treatment in QUAZAR AML-001, and practical recommendations for AE management based on guidance from international cancer consortiums, regulatory authorities, and the authors’ clinical experience treating patients in the trial.
Methods
QUAZAR AML-001 is an international, placebo-controlled randomized phase 3 study. Patients aged ≥ 55 years with AML and intermediate- or poor-risk cytogenetics at diagnosis, who had attained first complete remission (CR) or CR with incomplete blood count recovery (CRi) within 4 months before study entry, were randomized 1:1 to receive oral azacitidine 300 mg or placebo once-daily for 14 days in repeated 28-day cycles. Safety was assessed in all patients who received ≥ 1 dose of study drug.
Results
A total of 469 patients received oral azacitidine (n = 236) or placebo (n = 233). Median age was 68 years. Patients received a median of 12 (range 1–80) oral azacitidine treatment cycles or 6 (1–73) placebo cycles. Gastrointestinal AEs were common and typically low-grade. The most frequent grade 3–4 AEs during oral azacitidine therapy were hematologic events. AEs infrequently required permanent discontinuation of oral azacitidine (13%), suggesting they were effectively managed with use of concomitant medications and oral azacitidine dosing modifications.
Conclusion
Oral azacitidine maintenance had a generally favorable safety profile. Prophylaxis with antiemetic agents, and blood count monitoring every other week, are recommended for at least the first 2 oral azacitidine treatment cycles, and as needed thereafter. Awareness of the type, onset, and duration of common AEs, and implementation of effective AE management, may maximize treatment adherence and optimize the survival benefits of oral azacitidine AML remission maintenance therapy.
Trial registration. This trial is registered on clinicaltrials.gov: NCT01757535 as of December 2012
Oral azacitidine maintenance therapy for acute myeloid leukemia in first remission
Background: Although induction chemotherapy results in remission in many older patients with acute myeloid leukemia (AML), relapse is common and overall survival is poor.
Methods: We conducted a phase 3, randomized, double-blind, placebo-controlled trial of the oral formulation of azacitidine (CC-486, a hypomethylating agent that is not bioequivalent to injectable azacitidine), as maintenance therapy in patients with AML who were in first remission after intensive chemotherapy. Patients who were 55 years of age or older, were in complete remission with or without complete blood count recovery, and were not candidates for hematopoietic stem-cell transplantation were randomly assigned to receive CC-486 (300 mg) or placebo once daily for 14 days per 28-day cycle. The primary end point was overall survival. Secondary end points included relapse-free survival and health-related quality of life.
Results: A total of 472 patients underwent randomization; 238 were assigned to the CC-486 group and 234 were assigned to the placebo group. The median age was 68 years (range, 55 to 86). Median overall survival from the time of randomization was significantly longer with CC-486 than with placebo (24.7 months and 14.8 months, respectively; P<0.001). Median relapse-free survival was also significantly longer with CC-486 than with placebo (10.2 months and 4.8 months, respectively; P<0.001). Benefits of CC-486 with respect to overall and relapse-free survival were shown in most subgroups defined according to baseline characteristics. The most common adverse events in both groups were grade 1 or 2 gastrointestinal events. Common grade 3 or 4 adverse events were neutropenia (in 41% of patients in the CC-486 group and 24% of patients in the placebo group) and thrombocytopenia (in 22% and 21%, respectively). Overall health-related quality of life was preserved during CC-486 treatment.
Conclusions: CC-486 maintenance therapy was associated with significantly longer overall and relapse-free survival than placebo among older patients with AML who were in remission after chemotherapy. Side effects were mainly gastrointestinal symptoms and neutropenia. Quality-of-life measures were maintained throughout treatment
The Enzyme-linked Immunosorbent Assay: Accurate Detection of Red Blood Cell Antibodies in Autoimmune Hemolytic Anemia
A Single Institution Long-Term Experience Using Autologous Stem Cell Transplantation for the Management of Hodgkin’s Lymphoma.
LAG3 Inhibition Decreases AML-Induced Immunosuppression and Improves T Cell-Mediated Killing
A Phase 1, Open-Label, Dose-Escalation Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of Oral Azacitidine in Patients with Myelodysplastic Syndromes (MDS) or Acute Myelogenous Leukemia (AML).
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Efficacy and tolerability of lenalidomide (LEN) in patients (pts) 75 and older versus those younger than 75 with RBC transfusion-dependent low/int-1-risk MDS and del 5q
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Background: LEN is the approved treatment for pts with RBC transfusion-dependent Low/Int-1-risk MDS and del 5q. In 2 multicenter trials (MDS-003/-004) LEN lead to RBC transfusion independence (TI) for ≥ 26 wks in 35–58% of pts and cytogenetic response (CyR) in 25–73%. Most common grade (G) 3–4 adverse events (AE) were neutropenia and thrombocytopenia, a safety concern in elderly pts. We evaluated efficacy and tolerability of LEN in pts ≥ 75 y vs < 75 y in MDS-003/-004 trials. Methods: Pts received LEN 5 mg × 28 d, 10 mg × 21 d, or 10 mg × 28 d (all 28 d cycles). Dose reductions were required for G4 neutropenia (both trials) and platelet counts < 30 x 10
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/L (MDS-003) or < 25 x 10
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/L (MDS-004). Results: 32% of the 286 pts were ≥ 75 y. Baseline (BL) characteristics, LEN treatment, and optional G-CSF use are shown in Table. In pts ≥ 75 y vs 1 x 10
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/L was 0.7 vs 0.7 mo (P = NS) and to platelet counts > 100 x 10
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/L was 3.3 vs 1.7 mo (P = NS). 59% pts ≥ 75 y and 49% pts < 75 y discontinued LEN due to AE (33 vs 26%; P = NS), lack of effect (32 vs 49%; P = NS), or death (15 vs 6%; P = NS). Dose reduction and discontinuation rates are shown in Table. Conclusions: Pts ≥ 75 y and < 75 y had comparable response and AML progression rates. In pts ≥ 75 y, LEN appears to be well tolerated but the higher infection rate justifies close follow-up. [Table: see text