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Ferrata Storti Foundation
Haematologica 2019 Volume 104(4):700-709
Myelodysplastic Syndromes
Azacitidine with or without lenalidomide in higher risk myelodysplastic syndrome & low blast acute myeloid leukemia
Melita Kenealy,1,2 Mark Hertzberg,3 Warwick Benson,4 Kerry Taylor,5
Ilona Cunningham,6,7 Will Stevenson,8 Devendra Hiwase,9,10,11 Richard Eek,12 Daniela Zantomio,13 Steve Jong,14 Meaghan Wall,15,16,17 Piers Blombery,18,19 Tracey Gerber,20 Marlyse Debrincat,20,21,22 Diana Zannino20 and John F. Seymour18,23
1Cabrini Health, Melbourne; 2Monash University, Melbourne; 3Prince of Wales Hospital, Randwick, Sydney; 4Westmead Hospital, Sydney; 5Icon Cancer Care, Brisbane; 6Concord Hospital University of Sydney; 7University of Sydney; 8Royal North Shore Hospital, St Leonards; 9Haematology Department, Royal Adelaide Hospital; 10School of Medicine, Univeristy of Adelaide; 11Cancer Theme, South Australian Health and Medical Research (SAHMRI), Adelaide; 12Border Medical Oncology, Albury; 13Austin Health, Melbourne; 14Andrew Love Cancer Centre, University Hospital, Geelong; 15Victorian Cancer Cytogenetics Service, St Vincent’s Hospital, Fitzroy, Victoria; 16Department of Medicine, St Vincent’s Hospital, University of Melbourne, Fitzroy, Victoria; 17St Vincent’s Institute of Medical Research, Fitzroy, Victoria; 18Peter MacCallum Cancer Centre, Melbourne; 19Sir Peter MacCallum Department of Oncology, University of Melbourne; 20Australasian Leukaemia and Lymphoma Group, Richmond; 21Systems Biology and Personalised Medicine Division, The Walter and Eliza Hall Institute of Medical Research, Melbourne; 22Department of Medical Biology, University of Melbourne and 23University of Melbourne, Australia
ABSTRACT
Standard treatment for higher risk myelodysplastic syndromes, chronic myelomonocytic leukemia and low blast acute myeloid leukemia is azacitidine. In single arm studies, adding lenalidomide had been suggested to improve outcomes. The ALLG MDS4 phase II trial randomized such patients to standard azacitidine or combination azacitidine (75mg/m2/d days 1 to 5) with lenalidomide (10mg days 1-21 of 28-day cycle from cycle 3) to assess clinical benefit (alive without pro- gressive disease) at 12 months. A total of 160 patients were enrolled; median age 70.7 years (range 42.5-87.2), 31.3% female with 14% chron- ic myelomonocytic leukemia, 12% acute myeloid leukemia and 74% myelodysplastic syndromes. Adverse events were similar in both arms. There was excellent delivery of protocol therapy (median azacitidine cycles 11 both arms) with few dose reductions, delays or early cessa- tions. At median follow up 33.1 months (range 0.7-59.5), the rate of clin- ical benefit at 12 months was 65% azacitidine arm and 54% lenalido- mide+azacitidine arm (P=0.2). There was no difference in clinical bene- fit between each arm according to WHO diagnostic subgroup or IPSS-R. Overall response rate was 57% in azacitidine arm and 69% in lenalido- mide+azacitidine (P=0.14). There was no difference in progression- free or overall survival between the arms (each P>0.12). Although the com- bination of lenalidomide and azacitidine was tolerable, there was no improvement in clinical benefit, response rates or overall survival in higher risk myelodysplastic syndrome, chronic myelomonocytic leukemia or low blast acute myeloid leukemia patients compared to treatment with azacitidine alone. This trial was registered at www.anzc- tr.org.au as ACTRN12610000271000.
Correspondence:
MELITA KENEALY
melita.kenealy@thebloodunit.com.au
Received: July 10, 2018.
Accepted: November 23, 2018. Pre-published: December 13, 2018.
doi:10.3324/haematol.2018.201152
Check the online version for the most updated information on this article, online supplements, and information on authorship & disclosures: www.haematologica.org/content/104/4/700
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