Gemtuzumab ozogamicin with or without interleukin 11 in patients 65 years of age or older with untreated acute myeloid leukemia and high-risk myelodysplastic syndrome: comparison with idarubicin plus continuous-infusion, high-dose cytosine arabinoside

Blood ◽  
2002 ◽  
Vol 99 (12) ◽  
pp. 4343-4349 ◽  
Author(s):  
Elihu H. Estey ◽  
Peter F. Thall ◽  
Francis J. Giles ◽  
Xue-Mei Wang ◽  
Jorge E. Cortes ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myelodysplastic Syndrome ◽  
Cytosine Arabinoside ◽  
Myeloid Leukemia ◽  
Gemtuzumab Ozogamicin ◽  
High Dose ◽  
Newly Diagnosed ◽  
Covariate Effects ◽  
Interleukin 11 ◽  
Acute Myeloid

We investigated treatment with gemtuzumab ozogamicin (GO) in 51 patients aged 65 years or older with newly diagnosed acute myeloid leukemia (AML), refectory anemia (RA) with excess of blasts in transformation, or RA with excess blasts. GO was given in doses of 9 mg/m2 of body-surface area on days 1 and 8 or, therapeutically equivalently, on days 1 and 15, with or without interleukin 11 (IL-11; 15 μg/kg per day on days 3 to 28), with assignment to IL-11 treatment made randomly. Complete remission (CR) rates were 2 of 26 (8%) for GO without IL-11 and 9 of 25 (36%) for GO with IL-11. Regression analyses indicated that IL-11 was independently predictive of CR but not survival. We compared GO with or without IL-11 with idarubicin plus cytosine arabinoside (IA), as previously administered, in similar patients. The CR rate with IA was 15 of 31 (48%), and survival was superior with IA compared with GO with or without IL-11 (P = .03). Besides accounting for possible covariate effects on outcome, we also accounted for possible trial effects (TEs) arising because IA and GO with or without IL-11 were not arms of a randomized trial. Bayesian posterior probabilities that GO with or without IL-11 produced longer survival than IA, after accounting for covariates and TEs, were less than 0.01 in patients with abnormal cytogenetic findings (AC) and less than 0.15 in patients with normal cytogenetic findings (NC). Regarding CR, the analogous probabilities were less than 0.02 for GO without IL-11 (all cytogenetic groups), and for GO with IL-11, less than 0.25 for AC groups and about 0.50 for NC groups. TEs 2 to 5 times the magnitude of those previously observed would be needed to conclude that survival with GO with or without IL-11 is likely longer than with IA. Thus, there is little evidence to suggest that GO with or without IL-11 should be used instead of IA in older patients with newly diagnosed AML or myelodysplastic syndrome.

Sequential Combination of Gemtuzumab Ozogamicin and Standard Chemotherapy in Older Patients With Newly Diagnosed Acute Myeloid Leukemia: Results of a Randomized Phase III Trial by the EORTC and GIMEMA Consortium (AML-17)

2013 ◽  
Vol 31 (35) ◽  
pp. 4424-4430 ◽  
Author(s):  
Sergio Amadori ◽  
Stefan Suciu ◽  
Roberto Stasi ◽  
Helmut R. Salih ◽  
Dominik Selleslag ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Older Patients ◽  
Myeloid Leukemia ◽  
Gemtuzumab Ozogamicin ◽  
Phase Iii ◽  
Newly Diagnosed ◽  
Standard Chemotherapy ◽  
Sequential Combination ◽  
Grade 3 ◽  
Acute Myeloid

Purpose This randomized trial evaluated the efficacy and toxicity of sequential gemtuzumab ozogamicin (GO) and standard chemotherapy in older patients with newly diagnosed acute myeloid leukemia (AML). Patients and Methods Patients (n = 472) age 61 to 75 years were randomly assigned to induction chemotherapy with mitoxantrone, cytarabine, and etoposide preceded, or not, by a course of GO (6 mg/m2 on days 1 and 15). In remission, patients received two consolidation courses with or without GO (3 mg/m2 on day 0). The primary end point was overall survival (OS). Results The overall response rate was comparable between the two arms (GO, 45%; no GO, 49%), but induction and 60-day mortality rates were higher in the GO arm (17% v 12% and 22% v 18%, respectively). With median follow-up of 5.2 years, median OS was 7.1 months in the GO arm and 10 months in the no-GO arm (hazard ratio, 1.20; 95% CI, 0.99 to 1.45; P = .07). Other survival end points were similar in both arms. Grade 3 to 4 hematologic and liver toxicities were greater in the GO arm. Treatment with GO provided no benefit in any prognostic subgroup, with the possible exception of patients age < 70 years with secondary AML, but outcomes were significantly worse in the oldest age subgroup because of a higher risk of early mortality. Conclusion As used in this trial, the sequential combination of GO and standard chemotherapy provides no benefit for older patients with AML and is too toxic for those age ≥ 70 years.

scholarly journals Single-agent and combination biologics in acute myeloid leukemia

Hematology ◽  
2019 ◽  
Vol 2019 (1) ◽  
pp. 548-556 ◽  
Author(s):  
Guillaume Richard-Carpentier ◽  
Courtney D. DiNardo
Keyword(s):  
Acute Myeloid Leukemia ◽  
Older Patients ◽  
Myeloid Leukemia ◽  
Single Agent ◽  
Gemtuzumab Ozogamicin ◽  
Targeted Agents ◽  
Newly Diagnosed ◽  
Rational Drug ◽  
Genomic Characterization ◽  
Acute Myeloid

Abstract Acute myeloid leukemia (AML) is a heterogeneous malignancy characterized by recurrent genetic, epigenetic, and metabolic abnormalities. As a result of our increasing knowledge of the underlying biology of AML leading to rational drug development, several new targeted agents have been recently added to our therapeutic arsenal. The BCL2 inhibitor venetoclax in combination with low-dose cytarabine (LDAC) or hypomethylating agents (HMAs) is safe and effective in older patients with newly diagnosed AML ineligible for intensive chemotherapy. Glasdegib, a hedgehog pathway inhibitor, may be used in combination with LDAC for the same indication and improves survival compared with LDAC alone. In newly diagnosed, fit, older patients with therapy-related AML or AML with myelodysplasia-related changes, the liposome-encapsulated combination of daunorubicin and cytarabine (CPX-351) has shown superiority over the 7 + 3 regimen. The presence of an IDH1 or IDH2 mutation can be effectively targeted by ivosidenib or enasidenib, respectively. Gemtuzumab ozogamicin improves event-free survival in CD33+ patients with favorable or intermediate-risk cytogenetics. With new targeted agents available, comprehensive genomic characterization of AML at diagnosis and relapse is increasingly necessary to select optimal treatment. Herein, we review the new single-agent and combination biologics (omitting FLT3 inhibitors, which are discussed separately) and provide recommendations on how to best use and manage patients on these regimens in clinical practice.

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