title: The addition of gemtuzumab ozogamicin to low-dose Ara-C improves remission rate but does not significantly prolong survival in older patients with acute myeloid leukaemia: results from the LRF AML14 and NCRI AML16 pick-a-winner comparison.
abstract: The treatment of older patients with acute myeloid leukaemia, who are not considered suitable for conventional intensive therapy, is unsatisfactory. Low-dose Ara-C(LDAC) has been established as superior to best supportive care, but only benefits the few patients who enter complete remission. Alternative or additional treatments are required to improve the situation. This randomised trial compared the addition of the immunoconjugate, gemtuzumab ozogamicin (GO), at a dose of 5 mg on day 1 of each course of LDAC, with the intention of improving the remission rate and consequently survival. Between June 2004 and June 2010, 495 patients entered the randomisation. The addition of GO significantly improved the remission rate (30% vs 17%; odds ratio(OR) 0.48 (0.32-0.73); P=0.006), but not the 12 month overall survival (25% vs 27%). The reason for the induction benefit failing to improve OS was two-fold: survival of patients in the LDAC arm who did not enter remission and survival after relapse were both superior in the LDAC arm. Although the addition of GO to LDAC doubled the remission rate it did not improve overall survival. Maintaining remission in older patients remains elusive.
authors.affiliation: Department of Haematology, Cardiff University School of Medicine, Cardiff, UK.
authors.forename: A K
authors.initials: AK
authors.lastname: Burnett
authors.forename: R K
authors.initials: RK
authors.lastname: Hills
authors.forename: A E
authors.initials: AE
authors.lastname: Hunter
authors.forename: D
authors.initials: D
authors.lastname: Milligan
authors.forename: W J
authors.initials: WJ
authors.lastname: Kell
authors.forename: K
authors.initials: K
authors.lastname: Wheatley
authors.forename: J
authors.initials: J
authors.lastname: Yin
authors.forename: M F
authors.initials: MF
authors.lastname: McMullin
authors.forename: H
authors.initials: H
authors.lastname: Dignum
authors.forename: D
authors.initials: D
authors.lastname: Bowen
authors.forename: N H
authors.initials: NH
authors.lastname: Russell
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000617:Aminoglycosides / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003561:Cytarabine / Q000008:administration & dosage; D005260:Female; D000079982:Gemtuzumab; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D011379:Prognosis; D012074:Remission Induction; D015996:Survival Rate
chemical_list: D000617:Aminoglycosides; D061067:Antibodies, Monoclonal, Humanized; D003561:Cytarabine; D000079982:Gemtuzumab