Gemtuzumab ozogamicin in non-acute promyelocytic acute myeloid leukemia

Gemtuzumab ozogamicin (GO) has been used in relapsed, refractory and newly diagnosed acute myeloid leukemia (AML) as a single agent and in combination with intensive chemotherapy. Results of recent Phase III trials have led to its withdrawal in the USA although a beneficial effect of GO in genetically defined AML subgroups was evident.

This review examines the use of GO as a single agent or in combination with intensive chemotherapy in non-acute promyelocytic AML. The literature search was based on publications on GO indexed in the PubMed electronic database and selected meeting abstracts. GO has shown moderate activity as a single agent but promising activity in combination with intensive chemotherapy in refractory or relapsed AML. Relapsed AML defined molecularly by mutant nucleophosmin-1 without concurrent fms-related tyrosine kinase 3 (FLT3) internal tandem duplication seems to benefit most from GO. In newly diagnosed AML two up-front randomized Phase III trials evaluating GO in induction therapy failed to demonstrate an improvement in response and survival. Again, genetically defined subgroups may benefit.

Future challenges of personalized therapy in AML will be to integrate the signals from current subgroup analyses underlining the role of GO in genetically defined AML entities.