Salvage therapy for acute myeloid leukemia with fludarabine, cytarabine, and idarubicin with or without gemtuzumab ozogamicin and with concurrent or sequential G‐CSF

Abstract

The current salvage therapies for relapsed/refractory acute myeloid leukemia (AML) are unsatisfactory. Over the past 7 years, we have used two salvage regimens: fludarabine, cytarabine, and idarubicin with (FLAG-IM) or without gemtuzumab ozogamicin (GO) (9 mg/m 2 on Day 8) (FLAG-I) in relapsed/refractory AML. Three-quarters of patients also received concurrent G-CSF. Seventy-one patients were treated, 23 with FLAG-I and 48 with FLAG-IM. The median duration of follow-up was 30.6 months. The treatment groups were well balanced with median ages of 48 years (range 18-70) and 47 years (range 20-68), unfavorable cytogenetics in 57% and 35%, prior allogeneic stem cell transplant in 43% and 42%, and CR1 duration <1 year in 60% and 67%, respectively, for FLAG-I and FLAG-IM. The complete remission (CR) rate in the FLAG-I group was 39% with an additional 13% achieving a CRp [overall response rate (ORR) 52%]; the CR rate in the FLAG-IM group was 29% with an additional 27% achieving a CRp (ORR 56%). The median duration of response (DOR; 16.8 vs. 8.3 months), event-free survival (EFS; 7.4 vs. 4.1 months), and overall survival (OS; 8.8 vs. 5.0 months) trended to favor FLAG-I over FLAG-IM. The patients who received G-CSF concurrent with chemotherapy had superior overall response rate (ORR; 62% vs. 29%, P 5 0.026), median EFS (6.2 vs. 3.4 months, P 5 0.010), and OS (8.8 vs. 3.9 months, P 5 0.004) when compared with those who sequentially received G-CSF and chemotherapy, regardless of chemotherapy regimen. The addition of GO, at this dose and schedule, to FLAG-I failed to improve the outcomes in patients with relapsed/refractory AML. The patients who received G-CSF concurrently with chemotherapy had improved outcomes. Am. J. Hematol. 84:733-737, 2009. V

Day 15 bone marrow driven double induction in young adult patients with acute myeloid leukemia: Feasibility, toxicity, and therapeutic results

“…As DI, we decided to use the FLAG regimen, which has been proven as useful and safe for poor prognosis AML as well as for high-risk MDS. In addition, FLAG regimen delivers high-dose treatment without increasing overall toxicity, an approach which is of particular interest in patients potentially candidate to receive further chemotherapy, while being severely pancytopenic from previous conventional induction [29][30][31][32][33]. Of note, 30 of 33 patients (91%) were considered as clinically eligible to receive a second induction therapy, causes of noneligibility being in all cases severe active infections.…”

Improved outcome of patients with low‐ and intermediate‐risk cytogenetics acute myeloid leukemia (AML) in first relapse with gemtuzumab and cytarabine versus cytarabine

“…18,19 One randomized phase 2 prospective study from the ECOG 18 comparing 3 salvage regimens including 1 intermediate-dose cytarabine þ GO regimen was recently published and did not find any benefit from GO addition. In this study, response rates were extremely low (12% in the IHDAraC þ GO vs 7% and 4% in the 2 other IHDAraC-based regimens).…”

Fludarabine, Cytarabine and Gentuzumab Ozogamicin (FLA-GO) as Salvage Therapy and Bridge to Transplant in Adult Relapsed Acute Myeloid Leukemia (AML) Patients

“…Grade IV 3(11%) IM (fludarabine, ARA-C, idarubicin, GO) (39%) [24] or clofarabine (32%) [25]. In a recent report, the CR rate of 259 patients treated with FLA-idarubicin or FLAGO-idarubicin was 51%.…”

“…In most clinical trials the first dose of GO was administered on day 1 together with chemotherapy [31,38]. Others opted for a delayed administration so that GO was infused on the last day of chemotherapy [24,32,37,39]. The combination of methylprednisolone pre-medication and delayed GO infusion might explain why no serious infusion related adverse events were observed.…”