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/m^{2 2–45} or as 9 mg/m² fractionated into three 3 mg/m² doses^6,7) and in combination with chemotherapy^5–8.

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 dosing^2,5. 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