Outcome of patients with high risk Myelodysplastic Syndrome (MDS) and advanced Chronic Myelomonocytic Leukemia (CMML) treated with decitabine after azacitidine failure.
Outcome of patients with high risk MDS and CMML who failed treatment with azacitidine remains poor with a median survival of 6 months, without established therapy available except allogeneic hematopoietic stem cell transplantation. The objective of our study was to evaluate efficacy of decitabine after azacitidine failure in a relatively large patient cohort based on conflicting results with 0-28% response rates (RR) in this setting in small patient series. Thirty-six consecutive high risk MDS and CMML patients who received decitabine after azacitidine failure were retrospectively reviewed. Response was based on IWG 2006 criteria for MDS and CMML with WBC<13G/l and also included for proliferative CMML the evolution of WBC, splenomegaly (SMG) and extramedullary disease (EMD). Patients received a median number of 3 (range 1-27) cycles of decitabine and 12 patients received at least 6 cycles. Seven (19.4%) patients were responders including 3 marrow CR (mCR), 2 stable disease (SD) with HI-E, 1 SD with HI-N and HI-P and 1 SD with HI-N. In a CMML patient with SD, specific skin lesions resolved with decitabine. Responses were generally short lived (2-5 months) except 1 responder currently ongoing with +11 months follow up. Two non-responders had prolonged SD (without HI) of 21 and 27 months duration respectively. Median OS from onset of decitabine was 7.3 months, without significant difference between responders and non-responders. Treatment with decitabine after azacitidine failure yielded modest ORR (19.4%) with short response duration and poor OS. Thus, use of decitabine in such patients who failed or progressed after azacitidine cannot be recommended, underscoring the need for novel strategies in this setting.
Department of Hematology, Avicenne Hospital, AP-HP, University Paris 13, Bobigny, France.
Stéphanie
S
Harel
Department of Hematology, Avicenne Hospital, AP-HP, University Paris 13, Bobigny, France.
Amina
A
Cherait
Department of Hematogy, Lille University Hospital, Lille, France.
Céline
C
Berthon
Department of Hematogy, Lille University Hospital, Lille, France.
Christophe
C
Willekens
Department of Hematology, Grenoble University Hospital, Grenoble, France.
Sophie
S
Park
Department of Pharmacology, Avicenne Hospital, AP-HP, University Paris 13, Bobigny, France.
Marthe
M
Rigal
Department of Hematology, Avicenne Hospital, AP-HP, University Paris 13, Bobigny, France.
Sabine
S
Brechignac
Department of Hematology, Avicenne Hospital, AP-HP, University Paris 13, Bobigny, France.
Sylvain
S
Thépot
Department of Hematogy, Lille University Hospital, Lille, France.
Bruno
B
Quesnel
Department of Hematology, Avicenne Hospital, AP-HP, University Paris 13, Bobigny, France.
Claude
C
Gardin
Department of Hematology, Avicenne Hospital, AP-HP, University Paris 13, Bobigny, France; Department of Hematology Seniors, Saint Louis Hospital, AP-HP, University Paris 7, Paris, France.
Lionel
L
Adès
Department of Hematology, Avicenne Hospital, AP-HP, University Paris 13, Bobigny, France; Department of Hematology Seniors, Saint Louis Hospital, AP-HP, University Paris 7, Paris, France.
Pierre
P
Fenaux
Department of Hematology, Avicenne Hospital, AP-HP, University Paris 13, Bobigny, France. Electronic address: thorsten.braun@avc.aphp.fr.
Thorsten
T
Braun
D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D001374:Azacitidine / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D000077209:Decitabine; D018450:Disease Progression; D005260:Female; D006801:Humans; D015477:Leukemia, Myelomonocytic, Chronic / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors; D017211:Treatment Failure; D016896:Treatment Outcome
D000964:Antimetabolites, Antineoplastic; D000077209:Decitabine; D001374:Azacitidine
Azacitidine failure; CMML; Decitabine; MDS