Gemtuzumab, fludarabine, cytarabine, and cyclosporine in patients with newly diagnosed acute myelogenous leukemia or high‐risk myelodysplastic syndromes

Abstract

BACKGROUNDGemtuzumab 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).METHODSThe MFAC regimen was comprised of gemtuzumab (Mylotarg™) (6 mg/m2 intravenously [i.v.] on Day 1); fludarabine and ara‐C (15 mg/m2 and 0.5 g/m2, 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).RESULTSFifty‐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).CONCLUSIONSThe MFAC regimen may merit further study in patients with AML if measures to avoid and/or treat VOD can be incorporated into the regimen. Cancer 2003;97:1481–7. © 2003 American Cancer Society.DOI 10.1002/cncr.11239

High CD33-antigen loads in peripheral blood limit the efficacy of gemtuzumab ozogamicin (Mylotarg®) treatment in acute myeloid leukemia patients

“…However, so far, in most studies applying gemtuzumab-based combination regimens, gemtuzumab is given prior to or simultaneously with chemotherapy. [10][11][12][13][14][15] The use of gemtuzumab in a postremission regimen, combined with chemotherapy, has recently shown to be feasible and well-tolerated but needs further investigation. 16 To further improve the intracellular accumulation of gemtuzumab, drug efflux modulators such as cyclosporine A may be added to the treatment regimen as well.…”

Efficacy and resistance of gemtuzumab ozogamicin for acute myeloid leukemia

“…Cyclosporin A (CyA), one of the well-known MDR modifiers, has in fact been administered as an adjunct to GO-containing chemotherapy in the treatment of AML [55][56][57]. CyA did not improve response rate or survival, although veno-occlusive disease (VOD) was observed in some patients [55].…”

“…The MFAC regimen, consisted of GO (4.5 mg/m 2 on day 1), CyA (6 mg/kg on day 1), fludarabine (15 mg/m 2 every 12 h on days 2-4) and Ara-C (0.5 g/m 2 every 12 h on days 2-4), was conducted in 32 patients with relapsed/ refractory AML [56]. CR and CRp were achieved in 28 and 6 %, respectively.…”

“…Fifty-nine newly diagnosed patients (39 patients with AML, and 20 patients with RAEB/RAEBT) were treated with the MFAC regimen including GO (6 mg/m 2 on day 1); fludarabine (15 mg/m 2 on days 2-6), AraC (0.5 g/m 2 on days 2-6) and cyclosporine A (6 mg/kg on days 1 and 2) [56]. CR and CRp were achieved in 46 and 2 %, respectively.…”

The role of Gemtuzumab Ozogamicin in the treatment of acute myeloid leukemia patients

“…The major toxicities were infectious complications, hyperbilirubinemia and raised levels of transaminases. Four patients (7%) developed a VOD (Tsimberidou et al, 2003b).…”