Gemtuzumab, fludarabine, cytarabine, and cyclosporine in patients with newly diagnosed acute myelogenous leukemia or high-risk myelodysplastic syndromes.
BACKGROUND
Gemtuzumab is used to treat patients with previously untreated or recurrent acute myelogenous leukemia (AML). The fludarabine and cytarabine (ara-C) regimen is active in these patients. Resistance to gemtuzumab is associated with blast multidrug resistance (MDR). The objectives of this study were to evaluate the efficacy and toxicity of a combination regimen of gemtuzumab, fludarabine, ara-C, and the MDR modifier (cyclosporine [CyA]) in patients with previously untreated AML, refractory anemia with excess blasts (RAEB), or RAEB in transformation (RAEBT).


METHODS
The MFAC regimen was comprised of gemtuzumab (Mylotarg trade mark ) (6 mg/m(2) intravenously [i.v.] on Day 1); fludarabine and ara-C (15 mg/m(2) and 0.5 g/m(2), respectively, twice daily on Days 2-6); and CSA (6 mg/kg loading dose before gemtuzumab, followed by 16 mg/kg continuous i.v. infusion on Days 1 and 2).


RESULTS
Fifty-nine evaluable patients were treated: 39 patients (66%) had AML and 20 patients (34%) had RAEB/RAEBT. Their median age was 57 years (range, 27-76 years). The MFAC regimen induced complete remission (CR) in 27 patients (46%) and CR with incomplete platelet recovery (CRp) in 1 patient (2%). The median survival period is 8 months. At 12 months, the survival rate is 38% and the event-free survival rate in patients with CR/CRp is 27%. Infections complicated 38% of the courses of chemotherapy. Grade 3/4 toxicity included hyperbilirubinemia in 31% and transaminitis in 7% of the patients. Four patients (7%) developed hepatic venoocclusive disease (VOD).


CONCLUSIONS
The MFAC regimen may merit further study in patients with AML if measures to avoid and/or treat VOD can be incorporated into the regimen.
Tsimberidou
Apostolia
A
Department of Leukemia, University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Estey
Elihu
E
Cortes
Jorge
J
Thomas
Deborah
D
Faderl
Stefan
S
Verstovsek
Srdan
S
Garcia-Manero
Guillermo
G
Keating
Michael
M
Albitar
Maher
M
O'Brien
Susan
S
Kantarjian
Hagop
H
Giles
Francis
F
D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000032:analysis; D000617:Aminoglycosides; D000754:Anemia, Refractory, with Excess of Blasts / Q000188:drug therapy* / Q000473:pathology; D000900:Anti-Bacterial Agents / Q000008:administration & dosage; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001219:Aspartate Aminotransferases / Q000032:analysis; D016572:Cyclosporine / Q000008:administration & dosage; D003561:Cytarabine / Q000008:administration & dosage; D005260:Female; D000079982:Gemtuzumab; D006801:Humans; D006932:Hyperbilirubinemia / Q000139:chemically induced; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D013534:Survival; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives*
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D003561:Cytarabine; D016572:Cyclosporine; D000079982:Gemtuzumab; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D014740:Vidarabine; C024352:fludarabine