The treatment for acute myeloid leukemia (AML) has not changed dramatically for the last 20 years. Anti-CD33 monoclonal antibody therapy, the most prominent of which is gemtuzumab ozogamicin (GO), has been used over the last decade, in order to improve the results of patients with AML. It has been studied in a variety of contexts; at induction, consolidation and as re-induction after disease relapse. Several randomized controlled trials have evaluated the addition of anti-CD33 to chemotherapy as compared to chemotherapy alone for the treatment of AML.
Systematic review and meta-analysis of randomized controlled trials comparing addition of anti-CD33 to chemotherapy with chemotherapy alone in patients with AML, for either induction or post-remission therapy. Patients under 18 years old or those with acute promyelocytic leukemia were excluded. The Cochrane Library, MEDLINE, conference proceedings and references were searched until July 2012. Two reviewers appraised the quality of trials and extracted data. Outcomes assessed were: all-cause mortality at 30 days, all-cause mortality at the end of follow up, complete response and relapse rate. Relative risks (RR) were estimated and pooled.
Our search yielded 11 included trials, five of them published as abstracts, including 5239 patients. Most trials assessed GO and two trials assessed lintuzumab as the anti-CD33 agent. Dose and schedule differed between trials. Eight trials examined the effect of anti-CD33 in the induction setting: six assessed the addition of anti-CD33 to intensive induction (daunorubicin and cytarabine based) and two used low dose cytarabine in elderly patients. Three trials examined the addition of anti-CD33 in the post remission setting (one as consolidation, one as maintenance and one after relapse). When analyzing the addition of anti-CD33 in all settings together, there was no difference in all-cause mortality at 30 days or at the end of follow up between chemotherapy with anti-CD33 and chemotherapy alone (RR 1.15 [95% CI, 0.96–1.37, 7 trials], RR 0.96 [95% CI, 0.92–1.00, 8 trials] respectively). In the subgroup of favorable and intermediate risk AML, the addition of anti-CD33 had no effect on all-cause mortality, RR 0.94 (95% CI, 0.87–1.02, 3 trials)], however when analyzing the subgroup of favorable risk patients only, mortality was significantly reduced with the use of anti-CD33 (RR 0.60, 95% CI, 0.42–0.85, 2 trials). Treatment with anti-CD33 had no effect on complete remission rate, RR 1.05 (95% CI 0.96–1.14, 7 trials). Yet, it significantly reduced relapse rate, RR 0.90 (95% CI 0.84–0.96, 4 trials). There was not enough data to evaluate the incidence of veno-occlusive disease.
In conclusion, the addition of anti-CD33 to chemotherapy significantly decreased relapse rate, with no effect on all cause mortality. Yet, in the favorable risk subgroup, the use of anti-CD33 significantly reduced mortality. Further research is needed to confirm the beneficial effect in the favorable risk AML patients.
No relevant conflicts of interest to declare.
Asterisk with author names denotes non-ASH members.