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Gemtuzumab ozogamicin plus chemotherapy extended OS in AML
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The addition of gemtuzumab ozogamicin to induction chemotherapy significantly extended survival in adults with acute myeloid leukemia who did not have adverse cytogenetic characteristics, according to results of a meta-analysis.
Gemtuzumab ozogamicin (Mylotarg, Pfizer) was approved as the first antibody-directed chemotherapy for cancer treatment in 2000. However, it was withdrawn from the US market in 2010 due to the early termination of the SWOG S0106 trial, which showed excess early mortality among patients assigned gemtuzumab ozogamicin in 6-mg/m2 doses, according to background information provided by the researchers.
Robert K. Hills, MD, of the School of Medicine at Cardiff University in the United Kingdom, and colleagues identified five randomized controlled trials published through 2013 that compared gemtuzumab ozogamicin plus induction chemotherapy vs. chemotherapy alone.
The trials included 3,325 patients. Two of the trials (n=833) evaluated received gemtuzumab ozogamicin in 6-mg/m2 doses, and three trials (n=2,492) evaluated 3-mg/m2 doses.
Median follow-up in the pooled analysis was 60.8 months (interquartile range, 40.6-82.8).
The addition of gemtuzumab ozogamicin to induction chemotherapy was not associated with complete remission with or without complete peripheral count recovery (OR=0.91; 95% CI, 0.77-1.07). However, gemtuzumab ozogamicin was associated with significantly reduced risk for relapse (OR=0.81; 95% CI, 0.73-0.9) and improved OS at 5 years (OR=0.9; 95% CI, 0.82-0.98).
Hills and colleagues then evaluated patients according to the UK Medical Research Council cytogenetic characteristics classification.
Patients with favorable cytogenetic characteristics experienced a 20.7% absolute survival benefit with gemtuzumab ozogamicin at 6 years (OR=0.47; 95% CI, 0.31-0.73). Patients with intermediate characteristics experienced a 5.7% absolute benefit (OR=0.84; 95% CI, 0.75-0.95). Patients with adverse cytogenetic characterizes did not benefit from the treatment (absolute benefit, 2.2%; OR=0.99; 95% CI, 0.83-1.18).
Hills and colleagues noted that a significantly greater proportion of patients assigned gemtuzumab ozogamicin in 6-mg/m2 doses died within 30 days compared with patients assigned 3-mg/m2 doses, although the two doses conferred comparable survival benefits (P=.03). The excess early mortality observed in SWOG S0106 was not observed in the three trials that evaluated the 3-mg/m2 dose, according to researchers.
“With respect to the specific question of the addition of gemtuzumab ozogamicin to induction therapy in adults with AML, CD33 represents a legitimate therapeutic target and the addition of gemtuzumab ozogamicin significantly improves OS,” Hills and colleagues concluded. “These data provide strong evidence that consideration should be given to revision of its regulatory status with a view to making it available to patients.”
Disclosure: The researchers report no relevant financial disclosures.
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