Background: Compared with World Health Organization-defined acute myeloid leukaemia (AML) not otherwise specified, patients with AML with myelodysplasia-related changes (AML-MRC) are generally older and more likely to have poor-risk cytogenetics, leading to poor response and prognosis. More than one-half of all older (≥65 years) patients in the phase 3 AZA-AML-001 trial had newly diagnosed AML-MRC. Methods: We compared clinical outcomes for patients with AML-MRC treated with azacitidine or conventional care regimens (CCR; induction chemotherapy, low-dose cytarabine, or supportive care only) overall and within patient subgroups defined by cytogenetic risk (intermediate or poor) and age (65-74 years or ≥75 years). The same analyses were used to compare azacitidine with low-dose cytarabine in patients who had been preselected to low-dose cytarabine before they were randomized to receive azacitidine or CCR (ie, low-dose cytarabine). Results: Median overall survival was significantly prolonged with azacitidine (n = 129) versus CCR (n = 133): 8.9 versus 4.9 months (hazard ratio 0.74, [95%CI 0.57, 0.97]). Among patients with intermediate-risk cytogenetics, median overall survival with azacitidine was 16.4 months, and with CCR was 8.9 months (hazard ratio 0.73 [95%CI 0.48, 1.10]). Median overall survival was significantly improved for patients ages 65-74 years treated with azacitidine compared with those who received CCR (14.2 versus 7.3 months, respectively; hazard ratio 0.64 [95%CI 0.42, 0.97]). Within the subgroup of patients preselected to low-dose cytarabine before randomization, median overall survival with azacitidine was 9.5 months versus 4.6 months with low-dose cytarabine (hazard ratio 0.77 [95%CI 0.55, 1.09]). Within the low-dose cytarabine preselection group, patients with intermediate-risk cytogenetics who received azacitidine had a median overall survival of 14.1 months versus 6.4 months with low-dose cytarabine, and patients aged 65-74 years had median survival of 14.9 months versus 5.2 months, respectively. Overall response rates were similar with azacitidine and CCR (24.8% and 17.3%, respectively), but higher with azacitidine versus low-dose cytarabine (27.2% and 13.9%). Adverse events were generally comparable between the treatment arms. Conclusions: Azacitidine may be the preferred treatment for patients with AML-MRC who are not candidates for intensive chemotherapy, particularly patients ages 65-74 years and those with intermediate-risk cytogenetics. Trial registration: This study was registered at clinicalTrials.gov on February 16, 2010 ( NCT01074047 ).

Azacitidine improves clinical outcomes in older patients with acute myeloid leukaemia with myelodysplasia-related changes compared with conventional care regimens / Seymour, J. F.; Dohner, H.; Butrym, A.; Wierzbowska, A.; Selleslag, D.; Jang, J. H.; Kumar, R.; Cavenagh, J.; Schuh, A. C.; Candoni, A.; Recher, C.; Sandhu, I.; del Castillo, T. B.; Al-Ali, H. K.; Falantes, J.; Stone, R. M.; Minden, M. D.; Weaver, J.; Songer, S.; Beach, C. L.; Dombret, H.. - In: BMC CANCER. - ISSN 1471-2407. - 17:1(2017), pp. 852-862. [10.1186/s12885-017-3803-6]

Azacitidine improves clinical outcomes in older patients with acute myeloid leukaemia with myelodysplasia-related changes compared with conventional care regimens

Candoni A.;
2017

Abstract

Background: Compared with World Health Organization-defined acute myeloid leukaemia (AML) not otherwise specified, patients with AML with myelodysplasia-related changes (AML-MRC) are generally older and more likely to have poor-risk cytogenetics, leading to poor response and prognosis. More than one-half of all older (≥65 years) patients in the phase 3 AZA-AML-001 trial had newly diagnosed AML-MRC. Methods: We compared clinical outcomes for patients with AML-MRC treated with azacitidine or conventional care regimens (CCR; induction chemotherapy, low-dose cytarabine, or supportive care only) overall and within patient subgroups defined by cytogenetic risk (intermediate or poor) and age (65-74 years or ≥75 years). The same analyses were used to compare azacitidine with low-dose cytarabine in patients who had been preselected to low-dose cytarabine before they were randomized to receive azacitidine or CCR (ie, low-dose cytarabine). Results: Median overall survival was significantly prolonged with azacitidine (n = 129) versus CCR (n = 133): 8.9 versus 4.9 months (hazard ratio 0.74, [95%CI 0.57, 0.97]). Among patients with intermediate-risk cytogenetics, median overall survival with azacitidine was 16.4 months, and with CCR was 8.9 months (hazard ratio 0.73 [95%CI 0.48, 1.10]). Median overall survival was significantly improved for patients ages 65-74 years treated with azacitidine compared with those who received CCR (14.2 versus 7.3 months, respectively; hazard ratio 0.64 [95%CI 0.42, 0.97]). Within the subgroup of patients preselected to low-dose cytarabine before randomization, median overall survival with azacitidine was 9.5 months versus 4.6 months with low-dose cytarabine (hazard ratio 0.77 [95%CI 0.55, 1.09]). Within the low-dose cytarabine preselection group, patients with intermediate-risk cytogenetics who received azacitidine had a median overall survival of 14.1 months versus 6.4 months with low-dose cytarabine, and patients aged 65-74 years had median survival of 14.9 months versus 5.2 months, respectively. Overall response rates were similar with azacitidine and CCR (24.8% and 17.3%, respectively), but higher with azacitidine versus low-dose cytarabine (27.2% and 13.9%). Adverse events were generally comparable between the treatment arms. Conclusions: Azacitidine may be the preferred treatment for patients with AML-MRC who are not candidates for intensive chemotherapy, particularly patients ages 65-74 years and those with intermediate-risk cytogenetics. Trial registration: This study was registered at clinicalTrials.gov on February 16, 2010 ( NCT01074047 ).
2017
17
1
852
862
Azacitidine improves clinical outcomes in older patients with acute myeloid leukaemia with myelodysplasia-related changes compared with conventional care regimens / Seymour, J. F.; Dohner, H.; Butrym, A.; Wierzbowska, A.; Selleslag, D.; Jang, J. H.; Kumar, R.; Cavenagh, J.; Schuh, A. C.; Candoni, A.; Recher, C.; Sandhu, I.; del Castillo, T. B.; Al-Ali, H. K.; Falantes, J.; Stone, R. M.; Minden, M. D.; Weaver, J.; Songer, S.; Beach, C. L.; Dombret, H.. - In: BMC CANCER. - ISSN 1471-2407. - 17:1(2017), pp. 852-862. [10.1186/s12885-017-3803-6]
Seymour, J. F.; Dohner, H.; Butrym, A.; Wierzbowska, A.; Selleslag, D.; Jang, J. H.; Kumar, R.; Cavenagh, J.; Schuh, A. C.; Candoni, A.; Recher, C.; Sandhu, I.; del Castillo, T. B.; Al-Ali, H. K.; Falantes, J.; Stone, R. M.; Minden, M. D.; Weaver, J.; Songer, S.; Beach, C. L.; Dombret, H.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/1293995
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