Keywords: acute myeloid leukemia; immunotherapy; cardiotoxicity
ABSTRACT
Gemtuzumab ozogamicin (GO) is an anti-CD33 antibody-tumor antibiotic
conjugate with proven efficacy in pediatric and adult patients with
CD33+ acute myeloid leukemia (AML). Adverse effects commonly associated
with GO include hyperbilirubinemia, elevated transaminases, and
sinusoidal obstruction syndrome (SOS). Cardiotoxicity has not been a
commonly described adverse event. We describe two pediatric patients
with relapsed/refractory AML who received fractionated GO monotherapy
and subsequently developed severe acute left ventricular dysfunction.
Both patients achieved remission, recovered cardiac function with
medical therapy, and tolerated subsequent stem cell transplantation.
INTRODUCTION
Gemtuzumab ozogamicin (GO) is an anti-CD33 antibody-tumor antibiotic
conjugate used in the treatment of both de novo and
relapsed/refractory (r/r) pediatric acute myeloid leukemia (AML)with
demonstrated improvements in event free survival and relapse
risk1. In r/r pediatric AML, GO has been used both as
monotherapy (2.5-10 mg/m2 2–45 or
as 9 mg/m2 fractionated into three 3
mg/m2 doses6,7) and in combination
with chemotherapy5–8.
The main toxicities associated with GO include myelosuppression,
hyperbilirubinemia, transaminitis, and sinusoidal obstruction syndrome
(SOS). The incidence of SOS is directly associated with the absolute
single dose of GO, and fractionation of GO doses has been shown to
reduce SOS incidence 6,7,9,10.
Cardiotoxicity related to GO is rare, and only reported in pre-treated
r/r AML patients receiving unfractionated dosing2,5.
One study using two 7.5mg/m2 GO doses in 30 patients
with r/r pediatric AML found 4/30 patients had adverse effects in left
ventricle shortening fraction (LVSF) with 2/4 having grade 3 or 4
toxicity2. Another study using unfractionated GO in
r/r pediatric AML observed one death from worsening of pre-existing
cardiomyopathy with SOS5.
We have used unfractionated GO monotherapy in two pediatric patients
with r/r AML that subsequently developed life-threatening left
ventricular systolic dysfunction (LVSD). Herein, we present their
vignettes along with echocardiography and laboratory findings to
phenotype this rarely-described toxicity of an increasingly commonly
used immunotherapy.
CASE DESCRIPTIONS