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

Abstract

BACKGROUND: Acute myeloid leukemia (AML) in first relapse is associated with a poor outcome even when treated with intermediate-to high-dose cytarabine (IHDAraC). Gemtuzumab ozogamycin (GO) used as a single agent has clinical activity in relapsed and refractory AML. Various combination regimens of GO have been developed, but few data are available regarding their efficacy compared with IHDAraC-based regimens. METHODS: The authors performed a retrospective analysis of response and survival in 90 AML patients in first relapse treated with either IHDAraC (n ¼ 56) or IHDAraC þ GO (n ¼ 34). Patient characteristics of the two groups were comparable. RESULTS: Median follow-up was 37 months. Compared with IHDAraC, IHDAraC þ GO induction was associated with a better response rate (68% vs 45%, P ¼ .04), a better overall survival (median, 35 months vs 6 months, P ¼ .001), and a better event-free survival (24 months vs 6 months, P ¼ .002). This effect was limited to patients with low-risk and intermediate-risk cytogenetics. In multivariate analysis, age, cytogenetic risk, first complete remission duration, and the use of IHDAraC þ GO were independently associated with better results. CONCLUSIONS: This study showed that the addition of GO to IHDAraC is associated with a better efficacy for patients in first relapse of AML with low-or intermediate-risk cytogenetics. Prospective controlled studies of GO in this population are warranted. Patients with high-risk cytogenetics should be offered investigational new drugs. Cancer 2011;117:974-81.

Children's Oncology Group's 2013 blueprint for research: Acute myeloid leukemia

“…AAML0531 validated the benefits of response‐based therapy upon remission and the greater sensitivity and specificity of MRD over the use of morphology 8, 34, 35. AAML0531's randomization of GO outcome data have not yet been released, but concurrent with COG's CD33 targeting approach have been several adult groups' similar efforts 14, 16, 36–38. These saw benefit with CD33 targeting in the intermediate and favorable risk groups, predominantly composed of AML subtypes arising from more mature cells of origin, but none in patients with HR AML whose leukemias are of a more immature cell of origin.…”

Gemtuzumab ozogamicin in the treatment of adult acute myeloid leukemia

“…A number of GO-containing combination chemotherapies for relapsed and refractory AML have been reported (Table 3) [31][32][33][34][35][36][37][38][39][40][41][42]. The response rates observed in these studies range from 12% to 68% and appear to increase as time progresses.…”

“…However, the OS of the patients who received allogeneic HSCT was similar between the groups [36]. More recently, the outcomes of combined regimens with intermediate to high-dose cytarabine (IHDAraC) and IHDAraC with GO (3 -9 mg/m 2 , average 6 mg/m 2 ) were retrospectively compared in patients with a first relapse of AML [41]. The OR rate (GO vs no GO: 68% vs 45%; p = 0.04), EFS (24 months vs 6 months; p = 0.002) and OS (median, 35 months vs 6 months; p = 0.001) were significantly higher in the GO group.…”

Salvage therapy with high-dose cytarabine and mitoxantrone in combination with all-trans retinoic acid and gemtuzumab ozogamicin in acute myeloid leukemia refractory to first induction therapy

“…13,19,20 Based on these promising results, we combined GO with our previously established A-HAM regimen (GO-A-HAM) in patients refractory to one cycle of 3+7-based induction therapy. The main objectives of the study were to assess GO-A-HAM with regard to response rate, toxicity [including sinusoidal obstruction syndrome (SOS)] after allogeneic HCT, and survival.…”