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Extended survival and reduced risk of AML progression in erythroid-responsive lenalidomide-treated patients with lower-risk del(5q) MDS.

List AF, Bennett JM, Sekeres MA, Skikne B, Fu T, Shammo JM, Nimer SD, Knight RD, Giagounidis A, MDS-003 Study Investigato - Leukemia (2013)

Bottom Line: Time to acute myeloid leukemia (AML) progression was longer in patients achieving RBC-TI ≥ 8 weeks or any cytogenetic response versus non-responders (P=0.001 and P=0.0002, respectively).In a landmark multivariate analysis, RBC-TI ≥ 8 weeks was associated with prolonged OS (P<0.001) and a trend toward reduced relative risk of AML progression (P=0.080).Among these lower-risk MDS patients with del(5q), lenalidomide was associated with prolonged RBC-TI and cytogenetic responses, which were linked to improved OS and reduced risk of AML progression.

View Article: PubMed Central - PubMed

Affiliation: Department of Malignant Hematology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.

ABSTRACT
Lenalidomide is the approved treatment for patients with red blood cell (RBC) transfusion-dependent lower-risk myelodysplastic syndromes (MDS) and chromosome 5q deletion (del(5q)). We report the long-term outcomes (median follow-up 3.2 years) in patients treated with lenalidomide in the MDS-003 trial. RBC transfusion independence (TI) ≥ 8 weeks was achieved in 97 of 148 treated patients (65.5%), with a median response duration of 2.2 years. Partial or complete cytogenetic response was achieved by 63 of 88 evaluable patients (71.6%). Median overall survival (OS) was longer in patients achieving RBC-TI ≥ 8 weeks (4.3 vs 2.0 years in non-responders; P<0.0001) or cytogenetic response (4.9 vs 3.1 years in non-responders; P=0.010). Time to acute myeloid leukemia (AML) progression was longer in patients achieving RBC-TI ≥ 8 weeks or any cytogenetic response versus non-responders (P=0.001 and P=0.0002, respectively). In a landmark multivariate analysis, RBC-TI ≥ 8 weeks was associated with prolonged OS (P<0.001) and a trend toward reduced relative risk of AML progression (P=0.080). Among these lower-risk MDS patients with del(5q), lenalidomide was associated with prolonged RBC-TI and cytogenetic responses, which were linked to improved OS and reduced risk of AML progression.

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Related in: MedlinePlus

Time to acute myeloid leukemia (AML) progression with death as a competing risk according to: (a) baseline karyotype (one patient had no baseline karyotype available and was excluded from the analysis); (b) red blood cell-transfusion independence (RBC-TI) ⩾8 weeks response and (c) partial or complete cytogenetic response. Symbols indicate censored patients (+) or patients who died without AML (∘). Abbreviation: del(5q), chromosome 5q deletion.
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fig3: Time to acute myeloid leukemia (AML) progression with death as a competing risk according to: (a) baseline karyotype (one patient had no baseline karyotype available and was excluded from the analysis); (b) red blood cell-transfusion independence (RBC-TI) ⩾8 weeks response and (c) partial or complete cytogenetic response. Symbols indicate censored patients (+) or patients who died without AML (∘). Abbreviation: del(5q), chromosome 5q deletion.

Mentions: Seven patients (4.8%) progressed to a more advanced FAB subtype and 36 patients (24.5%) progressed to AML. Cumulative 1- and 5-year AML progression rates were 6.9% and 28.6%, respectively. AML progression occurred in 7 of 49 (14.3%) IPSS Low-risk patients (including 6 of 40 (15.0%) with 5q− syndrome), 20 of 69 (29.0%) Int-1-risk patients, 3 of 9 (33.3%) Int-2- or High-risk patients and 6 of 21 (28.6%) unclassified patients. Median follow-up duration for AML progression was 3.1 years. Median time to AML progression was not reached in patients with isolated del(5q) and was 4.1 years (95% CI, 2.6 to not evaluable) in patients with additional cytogenetic abnormalities (P=0.001). When analyzed with death as a competing risk, time to AML progression was longer in patients with isolated del(5q) compared with patients with additional cytogenetic abnormalities (P=0.005) (Figure 3, panel a).


Extended survival and reduced risk of AML progression in erythroid-responsive lenalidomide-treated patients with lower-risk del(5q) MDS.

List AF, Bennett JM, Sekeres MA, Skikne B, Fu T, Shammo JM, Nimer SD, Knight RD, Giagounidis A, MDS-003 Study Investigato - Leukemia (2013)

Time to acute myeloid leukemia (AML) progression with death as a competing risk according to: (a) baseline karyotype (one patient had no baseline karyotype available and was excluded from the analysis); (b) red blood cell-transfusion independence (RBC-TI) ⩾8 weeks response and (c) partial or complete cytogenetic response. Symbols indicate censored patients (+) or patients who died without AML (∘). Abbreviation: del(5q), chromosome 5q deletion.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4017258&req=5

fig3: Time to acute myeloid leukemia (AML) progression with death as a competing risk according to: (a) baseline karyotype (one patient had no baseline karyotype available and was excluded from the analysis); (b) red blood cell-transfusion independence (RBC-TI) ⩾8 weeks response and (c) partial or complete cytogenetic response. Symbols indicate censored patients (+) or patients who died without AML (∘). Abbreviation: del(5q), chromosome 5q deletion.
Mentions: Seven patients (4.8%) progressed to a more advanced FAB subtype and 36 patients (24.5%) progressed to AML. Cumulative 1- and 5-year AML progression rates were 6.9% and 28.6%, respectively. AML progression occurred in 7 of 49 (14.3%) IPSS Low-risk patients (including 6 of 40 (15.0%) with 5q− syndrome), 20 of 69 (29.0%) Int-1-risk patients, 3 of 9 (33.3%) Int-2- or High-risk patients and 6 of 21 (28.6%) unclassified patients. Median follow-up duration for AML progression was 3.1 years. Median time to AML progression was not reached in patients with isolated del(5q) and was 4.1 years (95% CI, 2.6 to not evaluable) in patients with additional cytogenetic abnormalities (P=0.001). When analyzed with death as a competing risk, time to AML progression was longer in patients with isolated del(5q) compared with patients with additional cytogenetic abnormalities (P=0.005) (Figure 3, panel a).

Bottom Line: Time to acute myeloid leukemia (AML) progression was longer in patients achieving RBC-TI ≥ 8 weeks or any cytogenetic response versus non-responders (P=0.001 and P=0.0002, respectively).In a landmark multivariate analysis, RBC-TI ≥ 8 weeks was associated with prolonged OS (P<0.001) and a trend toward reduced relative risk of AML progression (P=0.080).Among these lower-risk MDS patients with del(5q), lenalidomide was associated with prolonged RBC-TI and cytogenetic responses, which were linked to improved OS and reduced risk of AML progression.

View Article: PubMed Central - PubMed

Affiliation: Department of Malignant Hematology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.

ABSTRACT
Lenalidomide is the approved treatment for patients with red blood cell (RBC) transfusion-dependent lower-risk myelodysplastic syndromes (MDS) and chromosome 5q deletion (del(5q)). We report the long-term outcomes (median follow-up 3.2 years) in patients treated with lenalidomide in the MDS-003 trial. RBC transfusion independence (TI) ≥ 8 weeks was achieved in 97 of 148 treated patients (65.5%), with a median response duration of 2.2 years. Partial or complete cytogenetic response was achieved by 63 of 88 evaluable patients (71.6%). Median overall survival (OS) was longer in patients achieving RBC-TI ≥ 8 weeks (4.3 vs 2.0 years in non-responders; P<0.0001) or cytogenetic response (4.9 vs 3.1 years in non-responders; P=0.010). Time to acute myeloid leukemia (AML) progression was longer in patients achieving RBC-TI ≥ 8 weeks or any cytogenetic response versus non-responders (P=0.001 and P=0.0002, respectively). In a landmark multivariate analysis, RBC-TI ≥ 8 weeks was associated with prolonged OS (P<0.001) and a trend toward reduced relative risk of AML progression (P=0.080). Among these lower-risk MDS patients with del(5q), lenalidomide was associated with prolonged RBC-TI and cytogenetic responses, which were linked to improved OS and reduced risk of AML progression.

Show MeSH
Related in: MedlinePlus