Seventy to 80 % of patients with
acute myeloid leukemia (AML) achieve complete remission following intensive
chemotherapy, but more than 50 % of patients in remission subsequently relapse, which is often associated with clinical drug resistance.
Therapy based on
monoclonal antibodies (mAbs) has been developed to increase the selectivity of
cytotoxic agents by conjugating them with a mAb.
Gemtuzumab ozogamicin (GO) is a conjugate of a
cytotoxic agent, a
calicheamicin derivative, linked to a recombinant humanized mAb directed against the
CD33 antigen, which is expressed on
leukemia cells from more than 90 % of patients with AML. This conjugated mAb was introduced following promising results from phase I and II studies. However, the initial phase III study did not confirm the efficacy of GO in combination with conventional
chemotherapies. Several subsequent phase III studies have shown the efficacy of GO in favorable and intermediate risk AML. Several resistance mechanisms against GO have been reported. Multidrug resistant (MDR)
P-glycoprotein (P-gp), a trans-
membrane glycoprotein that pumps out many anti-leukemic agents from cells, also affects GO. For this reasons, GO has been used in combination with MDR modifiers, such as
cyclosporine, and in cases without P-gp. Several investigators have reported successful results of the use of GO in
acute promyelocytic leukemia (APL). GO has also been described as effective in cases relapsed
after treatment with
all-trans retinoic acid (ATRA),
arsenic acid and conventional chemotherapeutic agents. The efficacy of GO will be studied mainly in a favorable risk of AML, such as
core binding factor leukemia and APL. In addition, suitable combinations with other
chemotherapies and administration schedules should be discussed.